BackgroundRadiation-induced heart disease (RIHD) is a major late complication of thoracic radiotherapy. However, the mechanisms responsible for its long-term progression remain poorly understood. Conventional explanations, such as DNA damage, and oxidative stress, mainly focus on early radiation responses and fail to fully account for the prolonged latency and progressive myocardial remodeling observed in RIHD over years to decades.Main contentThis review proposes that persistent disruption of mitochondrial homeostasis represents a central link between early radiation-induced injury and late cardiac remodeling. We systematically summarize the major processes involved in radiation-induced mitochondrial dysfunction. These processes include mtDNA damage, respiratory chain impairment, sustained mitochondrial reactive oxygen species (mitoROS) accumulation, metabolic network remodeling, and defective mitochondrial clearance through mitophagy. We further discuss how acetylation, SUMOylation, and lactylation regulate these processes and contribute to the development and progression of RIHD. Building on this framework, we highlight emerging molecular targets, including NDP52, ATP5F1C, P4HB, and SH3GLB1, as well as the potential protective effects of bioactive compounds derived from traditional Chinese medicine, such as aloe-emodin and astragaloside IV, through restoration of mitochondrial homeostasis. By integrating mitochondrial dysfunction, post-translational modifications, and mitophagy into a unified pathological framework, this review provides new perspectives for early identification and therapeutic intervention in RIHD.Key conclusionsRIHD is not simply an oxidative stress-driven disorder but rather a chronic remodeling process shaped by the interplay among mitochondrial injury, post-translational modifications, and mitophagy dysregulation. This integrated framework links early subcellular alterations to late cardiac remodeling and provides a potential biological explanation for the long latency and progressive nature of RIHD. However, most current evidence is derived from adult models. Future research should specifically address childhood cancer survivors, as radiation exposure during critical periods of cardiac development may result in distinct long-term cardiovascular outcomes.

Introduction:Hyperhomocysteinemia (HHCY) is a well-recognized risk factor for cardiovascular diseases; however, the molecular mechanisms underlying HHCY-induced myocardial remodeling remain unclear. This study aimed to investigate the role of mitochondrial dysfunction and cardiomyocyte senescence in HHCY-associated myocardial remodeling and to explore the potential protective effects of AP39, a mitochondria-targeted hydrogen sulfide (H2S) donor. Methods:An integrated approach combining retrospective clinical analysis, animal models, and cellular experiments was employed. Associations between homocysteine (HCY) levels and left ventricular hypertrophy were analyzed in hypertensive patients. In vivo and in vitro models of HHCY were used to assess cardiac function, myocardial fibrosis, cellular senescence, mitochondrial dynamics, and underlying molecular mechanisms, with or without AP39 intervention. Results:Clinical analysis demonstrated that HHCY was significantly associated with left ventricular hypertrophy, and elevated HCY levels increased the risk of ventricular hypertrophy. In animal models, HHCY resulted in impaired cardiac function, evidenced by reduced left ventricular fractional shortening and increased left ventricular end-systolic diameter, accompanied by myocardial fibrosis and cardiomyocyte senescence. AP39 treatment markedly ameliorated these pathological changes. Mechanistically, AP39-derived H2S promoted S-sulfhydration of the NEDD8/CUL4B complex, thereby reducing ubiquitin-dependent degradation of FUNDC1. Upregulation of FUNDC1 restored mitochondrial dynamic homeostasis by weakening its interaction with DRP1, ultimately suppressing cardiomyocyte senescence. Discussion:These findings uncover a previously unrecognized mechanism by which AP39 preserves mitochondrial homeostasis through regulation of the FUNDC1-DRP1 axis via NEDD8/CUL4B-dependent S-sulfhydration. This study identifies a novel therapeutic target and provides mechanistic insight into HHCY-associated myocardial remodeling.

The core pathological mechanisms underlying cardiac hypertrophy and heart failure are closely linked to disturbances in energy metabolism. As pivotal metabolic intermediates in the tricarboxylic acid (TCA) cycle, ketone bodies and succinate engage in a dynamic functional interplay that exerts a critical regulatory influence on the progression of cardiovascular diseases. For the first time, this review systematically proposes the conceptual framework of the "ketone body-succinate metabolic axis," integrating recent advances in understanding their roles within cardiovascular system, and comprehensively elucidating the molecular mechanisms, cellular functions, and clinical relevance of this axis in cardiac hypertrophy and heart failure. Ketone bodies not only function as efficient alternative energy substrates under pathological conditions but also confer cardioprotective effects, including anti-inflammation and antioxidation actions. These benefits are mediated through multiple mechanisms, such as histone β-hydroxybutyrylation, suppression of the NLRP3 inflammasome, and activation of the GPR109A receptor. In contrast, succinate accumulates aberrantly under pathological conditions like ischemia and hypoxia, thereby promoting myocardial inflammation, fibrosis, and hypertrophy. These deleterious effects are driven by activation of the succinate receptor SUCNR1, stabilization of hypoxia-inducible factor-1α (HIF-1α), induction of mitochondrial reactive oxygen species (ROS) bursts, and regulation of protein succinylation. Together, ketone bodies and succinate constitute a tightly interconnected "yin-yang balance" regulatory network, characterized by shared metabolic nodes within the TCA cycle and antagonistic modulation of downstream signaling pathways, including inflammation and oxidative stress. Disruption of this dynamic balance represents a key mechanistic driver of disease progression from cardiac hypertrophy to heart failure. Furthermore, this review examines the regulatory influence of ketogenic diets and epigenetic modifications on the ketone body-succinate metabolic axis, and discusses the therapeutic potential and challenges of targeted interventions, such as ketone ester supplementation, SUCNR1 antagonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors. Collectively, these insights provide a novel conceptual framework and promising research direction for the development of precise metabolic therapies for cardiovascular diseases.

[This retracts the article DOI: 10.3892/etm.2021.10010.].

Methionine sulfoxide reductase B1 (MsrB1), a member of the selenoprotein family with a catalytic site containing a selenocysteine (Sec) residue, has been identified as an oncogene in colorectal cancer (CRC). However, the regulatory mechanisms of MsrB1 and the relationship between its oncogenic role and antioxidant capacity are not well understood. In this study, we show that either overexpression or suppression of MsrB1 in CRC cells leads to significant phenotypic changes, confirming its role in oncogenesis. To explore the molecular regulatory mechanisms of MsrB1, we used bioinformatic analyses to predict transcription factors within its promoter region, and validated these predictions using dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. These assays revealed that Krüppel-like factor 5 (KLF5), acting as a transcription factor, binds to the MsrB1 promoter and activates it. Additionally, through Weighted Gene Co-expression Network Analysis (WGCNA) and Co-IP experimental validation, we identified β-catenin, a key component of the Wnt signaling pathway, as being co-expressed with MsrB1. The interaction between MsrB1 and β-catenin leads to the activation of GPX4 transcription, a known ferroptosis marker, which results in the inhibition of ferroptosis and promotion of oncogenesis in CRC. In conclusion, this study elucidates the transcriptional regulatory mechanism of MsrB1 and its role in inhibiting ferroptosis in conjunction with β-catenin. These findings suggest that MsrB1 may be a promising predictive biomarker and therapeutic target for CRC, extending its role beyond that of a conventional antioxidant selenoprotein.

Background Diabetic cardiomyopathy (DCM) represents an important concern associated with diabetes, inhibiting pyroptosis has shown promising results in alleviating DCM symptoms. The objective of this work is to investigate the role and underlying mechanism of hydrogen sulfide (H2S) in the suppression of pyroptosis in the context of diabetic myocardial fibrosis (MF). Methods The effect of H2S on pyroptosis was detected using CCK-8, ELISA, and flow cytometry. The expression of Sestrin2 and its DNA methylation modification, as well as the quantification of pyroptosis-related proteins and the activation of the TLR4/MyD88/NF-κB signaling pathway, were measured using Western blot, ChIP, Immunofluorescence, and methylation-specific quantitative PCR. To establish a type 2 diabetes rat model, a high-fat diet was administered, followed by injection of streptozotocin (HFD/STZ). After five weeks, the rats received H2S treatment for four weeks, either with or without sh-Sestrin2. The effects of H2S treatment on myocardial function, tissue structure, and myocardial cell apoptosis were assessed. Furthermore, the CCK-8 assay was used to detect the cell viability induced by TGF-β. Cellular oxidative stress levels were measured by the ELISA method. Western blotting was applied to determine the protein expression levels of Collagen I, Fibronectin, α-SMA, NLRP3, caspase-1, GSDMD-N, and Sestrin2. Results H2S ameliorates HG-induced fibrosis, injury, pyroptosis, and inflammatory response of cardiac fibroblasts (CFs). H2S inhibits Sestrin2 methylation and up-regulates its expression through DNMT3a. H2S ameliorates HG-induced CFs pyroptosis and fibrosis through Sestrin2. Sestrin2 regulates HG-induced CFs pyroptosis and fibrosis through the TLR4/MyD88/NF-κB pathway. The myocardial tissue injury was improved after H2S treatment, and the results of the H2S treatment were reversed after knockdown of Sestrin2. In addition, TGF-β1 can induce an increase in the activity of cardiac fibroblasts and enhance cellular oxidative stress. Meanwhile, it significantly upregulates the expression of Collagen I, Fibronectin, α-SMA, as well as NLRP3, caspase-1, and GSDMD-N, and remarkably downregulates the expression of Sestrin2. However, H2S intervention can reverse the aforementioned phenomena. Conclusion H2S can suppress pyroptosis and ameliorate diabetic MF by inhibiting DNMT3a-mediated DNA methylation of Sestrin2 promoter through the TLR4/MyD88/NF-κB pathway.

Background Osteoarthritis (OA) is the most prevalent joint disorder globally, causing a substantial and increasing socioeconomic burden. Kojic acid (KA) presented potential biological roles in regulating inflammation and autophagy, which was implicated in OA progression. However, its role in chondrocytes and OA has not been reported. To do so, this study aims to explore the chondroprotective effect of KA and elucidate its regulatory mechanisms. Methods IL-1β in vitro was used to induce OA-like phenotypes. Cell viability was measured by cell counting kit-8 assay. RT-qPCR, western blotting, as well as immunofluorescence staining were used to assess protein and RNA expression of inflammatory (COX2 and iNOS), catabolic (MMP13 and MMP3), anabolic (collagen II, aggrecan and SOX9), and signaling pathways factors. Destabilized medial meniscus (DMM) surgery was adopted to build OA model in vivo. After consecutive 8 weeks of intra-articular injection of KA, X-ray, μ-CT, histological staining, as well as immunohistochemistry staining were adopted to evaluate effects of KA on articular cartilage in vivo. Results KA did not affect chondrocyte viability. KA notably elevated anabolic factors expression, simultaneously, inhibited catabolic and inflammatory factors expression in vitro. Mechanistically, KA significantly suppressed the activated NF-κB and PI3K/AKT/mTOR signaling pathways. Moreover, impaired autophagy was restored by KA. Inhibition of autophagy by 3-MA diminished the chondroprotective effect of KA. Intra-articular injection of KA can significantly alleviate DMM-induced cartilage damage in vivo. Conclusion Collectively, our work is the first to demonstrate that KA can alleviate osteoarthritis by attenuatinginflammationand restoring impaired autophagy through regulating relevant signaling pathways. This in vivo and in vitro study provides strong evidence supportingKA as a novel and valuable approach for treating OA.

Cardiovascular disease (CVD) is currently a major factor affecting human physical and mental health. In recent years, the relationship between intracellular Ca2+ and CVD has been extensively studied. Ca2+ movement across the mitochondrial inner membrane plays a vital role as an intracellular messenger, regulating energy metabolism and calcium homeostasis. It is also involved in pathological processes such as cardiomyocyte apoptosis, hypertrophy and fibrosis in CVD. The selective mitochondrial calcium uniporter complex (MCU complex) located in the inner membrane is essential for mitochondrial Ca2+ uptake. Therefore, the MCU complex is a potential therapeutic target for CVD. In this review, recent research progress on the pathophysiological mechanisms and therapeutic potential of the MCU complex in various CVDs was summarized, including myocardial ischemia‑reperfusion injury, pulmonary arterial hypertension, other peripheral vascular diseases, myocardial remodeling and arrhythmias. This review contributes to a deeper understanding of these mechanisms at the molecular level and highlights potential intervention targets for CVD treatment in clinical practice.

Shaoyao Gancao Decoction(SGD) is one of the prescriptions included in the Catalogue of Ancient Classical Prescriptions(First Batch) published by the National Administration of Traditional Chinese Medicine in 2018. It is composed of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle. Experiments and clinical cases have proved that SGD has anti-inflammatory, pain-relieving, antispasmodic, and liver-protecting effects. It is widely used in the clinical treatment of diseases, demonstrating definite effects on digestive system diseases. By reviewing the literature on SGD in recent years, this paper summarizes the applications of SGD in the treatment of digestive system diseases from three aspects of basic prescription and syndrome analysis, clinical application, and mechanism to expounds the research status in this field. Furthermore, this paper put forward the shortcomings and improvement methods of the available studies, aiming to provide reference for the application of SGD in treating digestive system diseases and the research and development of SGD preparations.

Background: Through bioinformatics analysis, this study explores the interactions and biological pathways involving metabolomic products in patients diagnosed with coronary heart disease (CHD). Methods: A comprehensive search for relevant studies focusing on metabolomics analysis in CHD patients was conducted across databases including CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Nature, Web of Science, Springer, and Science Direct. Metabolites reported in the literature underwent statistical analysis and summarization, with the identification of differential metabolites. The pathways associated with these metabolites were examined using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular annotation of metabolites and their relationships with enzymes or transporters were elucidated through analysis with the Human Metabolome Database (HMDB). Visual representation of the properties related to these metabolites was achieved using Metabolomics Pathway Analysis (metPA). Results: A total of 13 literatures satisfying the criteria for enrollment were included. A total of 91 metabolites related to CHD were preliminarily screened, and 87 effective metabolites were obtained after the unrecognized metabolites were excluded. A total of 45 pathways were involved. Through the topology analysis (TPA) of pathways, their influence values were calculated, and 13 major metabolic pathways were selected. The pathways such as Phenylalanine, tyrosine, and tryptophan biosynthesis, Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, and Glycine, serine, and threonine metabolism primarily involved the regulation of processes and metabolites related to inflammation, oxidative stress, one-carbon metabolism, energy metabolism, lipid metabolism, immune regulation, and nitric oxide expression. Conclusion: Multiple pathways, including Phenylalanine, tyrosine, and tryptophan biosynthesis, Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, and Glycine, serine, and threonine metabolism, were involved in the occurrence of CHD. The occurrence of CHD is primarily associated with the regulation of processes and metabolites related to inflammation, oxidative stress, one-carbon metabolism, energy metabolism, lipid metabolism, immune regulation, and nitric oxide expression.

Doxorubicin induces myocardial injury and fibrosis. Still, no effective interventions are available. AP39 is an H2S donor that explicitly targets mitochondria. This study investigated whether AP39 could improve doxorubicin-induced myocardial fibrosis. Doxorubicin induced significant myocardial fibrosis while suppressing mitophagy-related proteins and elevating pyroptosis-related proteins. Conversely, AP39 reverses these effects, enhancing mitophagy and inhibiting pyroptosis. In vitro experiments revealed that AP39 inhibited H9c2 cardiomyocyte pyroptosis, improved doxorubicin-induced impairment of mitophagy, reduced ROS levels, ameliorated the mitochondrial membrane potential, and upregulated AMPK-ULK1-FUNDC1 expression. In contrast, AMPK inhibitor (dorsomorphin) and ULK1 inhibitor (SBI-0206965) reversed AP39 antagonism of doxorubicin-induced FUNDC1-mediated impairment of mitophagy and secondary cardiomyocyte pyroptosis. These results suggest that mitochondria-targeted H2S can antagonize doxorubicin-induced pyroptosis and impaired mitophagy in cardiomyocytes via AMPK-ULK1-FUNDC1 and ameliorated myocardial fibrosis and remodeling.

Sulfur dioxide (SO2), a novel endogenous gas signaling molecule, is involved in the regulation of cardiac function. Exerting a key role in progression of hyperthyroidism-induced cardiomyopathy (HTC), myocardial fibrosis is mainly caused by myocardial apoptosis, leading to poor treatment outcomes and prognoses. This study aimed to investigate the effect of SO2 on the hyperthyroidism-induced myocardial fibrosis and the underlying regulatory mechanisms. Elisa, Masson staining, Western-Blot, transmission electron microscope, and immunofluorescence were employed to evaluate the myocardial interstitial collagen deposition, endoplasmic reticulum stress (ERS), apoptosis, changes in endogenous SO2, and Hippo pathways from in vitro and in vivo experiments. The study results indicated that the hyperthyroidism-induced myocardial fibrosis was accompanied by decreased cardiac function, and down-regulated ERS, apoptosis, and endogenous SO2-producing enzyme aspartate aminotransferase (AAT)1/2 in cardiac myocytes. In contrast, exogenous SO2 donors improved cardiac function, reduced myocardial interstitial collagen deposition, up-regulated AAT1/2, antagonized ERS and apoptosis, and inhibited excessive activation of Hippo pathway in hyperthyroid rats. In conclusion, the results herein suggested that SO2 inhibited the overactivation of the Hippo pathway, antagonized ERS and apoptosis, and alleviated myocardial fibrosis in hyperthyroid rats. Therefore, this study was expected to identify intervention targets and new strategies for prevention and treatment of HTC.

Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease. According to the American Cancer Society's 2021 cancer data report, new cases of CML account for about 15% of all leukemias. CML is generally divided into three stages: chronic phase, accelerated phase, and blast phase. Nearly 90% of patients are diagnosed as a chronic phase. Allogeneic stem cell transplantation and chemotherapeutic drugs, such as interferon IFN-α were used as the earliest treatments for CML. However, they could generate obvious side effects, and scientists had to seek new treatments for CML. A new era of targeted therapy for CML began with the introduction of imatinib, the first-generation BCR-ABL kinase inhibitor. However, the ensuing drug resistance and mutant strains led by T315I limited the further use of imatinib. With the continuous advancement of research, tyrosine kinase inhibitors (TKI) and BCR-ABL protein degraders with novel structures and therapeutic mechanisms have been discovered. From biological macromolecules to classical target protein inhibitors, a growing number of compounds are being developed to treat chronic myelogenous leukemia. In this review, we focus on summarizing the current situation of a series of candidate small-molecule drugs in CML therapy, including TKIs and BCR-ABL protein degrader. The examples provided herein describe the pharmacology activity of small-molecule drugs. These drugs will provide new enlightenment for future treatment directions.

Hypothyroidism alone can lead to myocardial fibrosis and result in heart failure, but traditional hormone replacement therapy does not improve the fibrotic situation. Hydrogen sulfide (H2S), a new gas signaling molecule, possesses anti-inflammatory, antioxidant, and anti-fibrotic capabilities. Whether H2S could improve hypothyroidism-induced myocardial fibrosis are not yet studied. In our study, H2S could decrease collagen deposition in the myocardial tissue of rats caused by hypothyroidism. Furthermore, in hypothyroidism-induced rats, we found that H2S could enhance cystathionine-gamma-lyase (CSE), not cystathionine β-synthase (CBS), protein expressions. Finally, we noticed that H2S could elevate autophagy levels and inhibit the transforming growth factor-β1 (TGF-β1) signal transduction pathway. In conclusion, our experiments not only suggest that H2S could alleviate hypothyroidism-induced myocardial fibrosis by activating autophagy and suppressing TGF-β1/SMAD family member 2 (Smad 2) signal transduction pathway, but also show that it can be used as a complementary treatment to conventional hormone therapy.

BACKGROUND AND PURPOSE:Research has revealed the involvement of mitochondrial autophagy and iron death in the pathogenesis of myocardial fibrosis. The objective of this study is to investigate whether the mitochondrial-targeted H2S donor AP39 inhibits mitochondrial autophagy and antagonizes myocardial cell iron death through the PINK1/Parkin pathway, thereby improving myocardial fibrosis in rats with myocardial infarction.EXPERIMENTAL APPROACH:A rat model of myocardial infarction was created by intraperitoneal injection of a high dose of isoproterenol, and H9c2 myocardial cells were subjected to hypoxic injury induced by CoCl2. Western blot, RT-PCR, transmission electron microscopy, immunohistochemistry, as well as echocardiography, and studies on isolated hearts were employed.KEY RESULTS:In the hearts of rats with myocardial infarction, there was a significant accumulation of interstitial collagen fibers, accompanied by downregulation of CSE protein expression, activation of the PINK1/Parkin signaling pathway, and activation of mitochondrial autophagy. Intervention with AP39 resulted in a significant improvement of the aforementioned changes, which could be reversed by the addition of PAG. Similar results were observed in vitro experiments. Furthermore, the addition of CCCP reversed the antagonistic effect of AP39 on myocardial cell iron death, while the addition of RSL3 reversed the inhibitory effect of AP39 on collagen production in myocardial cells.CONCLUSION AND IMPLICATIONS:The mitochondrial-targeted H2S donor AP39 can inhibit mitochondrial autophagy through the PINK1/Parkin pathway, antagonize myocardial cell iron death, and improve myocardial fibrosis in rats with myocardial infarction.

Abstract Our previous studies have shown that hyper-homocysteinemia (HHCY) can induce myocardial fibrosis and remodeling, but the underlying mechanisms are not well understood. AP39, a newly synthesized mitochondrial-targeted H2S donor, has been shown to inhibit myocardial cell injury and endothelial cell aging, but its specific regulatory mechanisms are unclear. Therefore, in this study, we constructed an animal model of HHCY-induced myocardial remodeling in SD rats by drinking water containing L-methionine (10g/L), and observed that HHCY rats had decreased cardiac function, significant collagen fiber deposition in myocardial tissue, increased senescent cells in myocardial tissue, inhibited Mitophagy, and significantly imbalanced mitochondrial dynamics. AP39 intervention (100nM) could significantly reverse the above phenomena; similar changes were observed in vitro experiments. RNA-seq technology and quantitative PCR on H9c2 myocardial cells stimulated by HHCY showed that AP39 intervention could reverse the down-regulation of FUNDC1-mediated Mitophagy induced by HHCY, and RNA interference of FUNFC1 could eliminate the effect of AP39. In conclusion, the mitochondrial-targeted H2S donor AP39 may improve myocardial mitochondrial dynamics and stress-induced senescence by up-regulating FUNDC1-mediated Mitophagy, thereby improving HHCY-induced myocardial remodeling.

This study aimed to assess the effects of exogenous hydrogen sulfide (H2S) on abdominal aorta coarctation (AAC) induced myocardial fibrosis (MF) and autophagy in rats. Forty-four Sprague-Dawley rats were randomly divided into control group, AAC group, AAC + H2S group, and H2S control group. After a model of rats with AAC was built surgically, AAC + H2S group and H2S group were injected intraperitoneally with H2S (100 μmol/kg) daily. The rats in the control group and the AAC group were injected with the same amount of PBS. We observed that H2S can improve left ventricular function and the deposition of myocardial collagen fibers, inhibit pyroptosis, down-regulate the expression of P-eif2α in myocardial tissue, and inhibit cell autophagy by activating the phosphatidylinositol 3-kinase (PI3K)/AKT1 signaling pathway (p < 0.05). In addition, angiotensin II (1 μM) H9c2 cardiomyocytes were injured in vitro experiments, and it was also observed that pyroptosis was inhibited after H2S (400 μmol/kg) intervention, the expression of P-eif2α in cardiomyocytes was significantly down-regulated, and the PI3K/AKT1 signaling pathway was activated at the same time. Therefore, increasing the expression of P-eif2α reverses the activation of the PI3K/AKT1 signaling pathway by H2S. In conclusion, these findings suggest that exogenous H2S can ameliorate MF in rats with AAC by inhibiting pyroptosis, and the mechanism may be associated with inhibiting the phosphorylation of eif2α and activating the PI3K/AKT1 signaling pathway to inhibit excessive cell autophagy.

目的:观察二氧化硫(SO2)对大鼠急性心肌缺血损伤后心肌纤维化(MF)的影响,并探讨其作用机制.方法:24只雄性SD大鼠随机分为对照组(不处理)、异丙肾上腺素(ISO)组(给予ISO)、ISO+SO2 组(给予ISO+SO2)和SO2 组(给予SO2),每组6只.ISO组和ISO+SO2 组大鼠连续2 d腹腔注射大剂量ISO(50 mg·kg-1·d-1)构建急性心肌缺血损伤模型.造模成功后,ISO+SO2组和SO2 组大鼠给予Na2SO3 溶液(0.54 mmol·kg-1·d-1)和NaHSO3溶液(0.18 mmol·kg-1·d-1),连续4周,对照组和ISO组大鼠给予等量生理盐水.检测4组大鼠血浆肌钙蛋白水平和心电图,超声心动图检测4组大鼠左室短轴缩短率(LVFS)和左室射血分数(LVEF),Masson染色检测4组大鼠心肌组织中胶原沉积情况并计算胶原体积分数(CVF),Tunel染色检测 4组大鼠心肌细胞凋亡率,Western blotting法检测4组大鼠心肌组织中自噬相关蛋白3(Atg3)、自噬相关蛋白5(Atg5)、自噬相关蛋白16L1(Atg16L1)、含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase-3)、含半胱氨酸的天冬氨酸蛋白水解酶9(Caspase-9)、基质金属蛋白酶8(MMP-8)和金属蛋白酶组织抑制物2(TIMP-2)蛋白表达水平.结果:与对照组比较,ISO组和ISO+SO2组大鼠心电图ST段明显抬高,肌钙蛋白水平升高(P<0.05),提示急性心肌缺血损伤大鼠造模成功;与对照组比较,ISO组大鼠LVFS和LVEF降低(P<0.05),心肌组织中CVF升高(P<0.05),心肌细胞凋亡率升高(P<0.05),心肌组织中Atg3、Atg5、Atg16L1、Caspase-3、Caspase-9和MMP-8蛋白表达水平升高(P<0.05),TIMP-2蛋白表达水平降低(P<0.05);与ISO组比较,ISO+SO2 组大鼠LVFS和LVEF升高(P<0.05),心肌组织中 CVF降低(P<0.05),心肌细胞凋亡率降低(P<0.05),心肌组织中 Atg3、Atg5、Atg16L1、Caspase-3、Caspase-9和MMP-8蛋白表达水平降低(P<0.05),TIMP-2蛋白表达水平升高(P<0.05).结论:SO2可以改善大鼠急性心肌缺血损伤后MF,其机制可能与抑制心肌细胞过度自噬并减少心肌细胞凋亡有关.

The recent study by Mockel et al. [ [1] Mockel M. Pudasaini S. Baberg H.T. Levenson B. Malzahn J. Mansky T. Michels G. Gunster C. Jeschke E. Oral anticoagulation in heart failure complicated by atrial fibrillation: a nationwide routine data study. Int. J. Cardiol. 2023; 131434 Google Scholar ] on the use of oral anticoagulants (OACs) in patients with heart failure (HF) and atrial fibrillation (AF) deeply intrigued me, and in fact, there should be widespread attention to how to better select anticoagulants for patients with HF combined with AF. This is a retrospective study primarily focused on 180,316 patients from the claims of Allgemeine Ortskrankenkasse (AOK) between January 1, 2017, and December 31, 2019, aiming to elucidate the benefits of using oral anticoagulants in patients with HF and AF, and whether oral new oral anticoagulants (NOACs) are superior in this regard.