Objective:Myocardial ischemia-reperfusion injury (MIRI) is a critical clinical challenge in cardiovascular disease management. Sanshen Dan (SSD), a clinically validated traditional Chinese medicine formula, exerts therapeutic effects on MIRI, but its chemical composition and underlying mechanism remain unclear. This study aimed to systematically elucidate the cardioprotective mechanism of SSD against MIRI using an integrated strategy. Methods:An integrated approach combining serum pharmacochemistry, network pharmacology, machine learning, molecular docking, and molecular dynamics simulation was adopted. 1. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to identify blood-absorbed components of SSD after oral administration to Sprague-Dawley rats. 2. Potential targets of these components were predicted via public databases, and overlapping targets with MIRI-related genes were screened to construct a compound-target network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. 3. Three machine learning algorithms (random forest, SVM-RFE, LASSO regression) were applied to identify core therapeutic targets. 4. Molecular docking and 100 ns molecular dynamics simulations were performed to verify the binding affinity and stability of ligand-receptor complexes. Results:A total of 44 blood-absorbed active components of SSD were identified, including flavonoids, saponins, lignans, and phenolic acids. A total of 392 potential therapeutic targets were screened out, which were mainly enriched in apoptosis, HIF-1, TNF-α, and cAMP signaling pathways. Machine learning analysis identified Mmp14, Htr2b, and Ctnnb1 as core targets, and the constructed nomogram model showed excellent predictive performance (AUC = 1, C-index = 1). Molecular docking indicated that 6 core components (eg, Kaempferide-4'-methyl ether-3-glucoside, Licurazide) exhibited strong binding affinity to the core targets, and molecular dynamics simulations confirmed the high stability of these complexes, with mean binding free energy ranging from -20.58 kcal/mol to -34.31 kcal/mol. Conclusion:SSD exerts cardioprotective effects against MIRI via a "multi-component, multi-target, multi-pathway" mode. Its core blood-absorbed components may alleviate MIRI by regulating core targets including Mmp14 and Ctnnb1, and modulating key signaling pathways such as TNF-α and HIF-1. This study provides a scientific basis for the clinical application of SSD and further exploration of traditional Chinese medicine compound formulas.

PURPOSE:The objective of this study is to investigate the efficacy of the Shenlian (SL) decoction on regulating cellular pyroptosis and macrophage M1 polarization in the treatment of diabetic nephropathy (DN), and to elucidate its mechanism of action through the use of animal and cellular experiments. METHODS:The potential targets for SL decoction were predicted using the TCMSP and Swiss Target databases. The differential genes for DN were obtained using the GeneCards database, and potential mechanisms for the treatment of DN with SL decoction were explored through enrichment analysis. The efficacy of SL decoction in the treatment of DN and its regulation of macrophage polarization and pyroptosis were evaluated in vivo using db/db mice. The RAW264.7 cell line and the TCMK-1 cell line were cultured in vitro. The objective was to investigate the effect of SL decoction on the inhibition of M1 macrophage polarization and scorched death of renal tubular epithelial cells (TECs). RESULTS:The results of the enrichment analysis indicated that the Toll-like signaling pathway was a principal pathway in the treatment of DN with SL decoction. The results of animal and cellular experiments demonstrated that SL decoction has the potential to enhance renal function in patients with DN, while simultaneously reducing the concentration of serum inflammatory factors. Additionally, it was observed that SL decoction could inhibit the infiltration of macrophages and the polarization of macrophages into the M1 phenotype. Furthermore, the activation of the TLR4 signaling pathway and the pyroptosis of renal tubular cells were also inhibited by SL decoction. CONCLUSION:This study employed network pharmacology and in vivo and in vitro experiments to confirm that SL decoction can improve renal function in patients with DN. The results demonstrated that the mechanism of action of SL decoction is related to regulating the M1 polarization of macrophages in the DN kidney and inhibiting the pyroptosis of renal TECs.

Background: Shenlian (SL) decoction, a renowned traditional Chinese formula for diabetes mellitus, has also been employed to treat intestinal disorders. Previous studies have demonstrated the efficacy of SL decoction in regulating blood glucose and intestinal bacteria. Nevertheless, further analysis is required to elucidate the mechanistic link between SL decoction–mediated improvement of intestinal function and treatment of Type 2 diabetes mellitus (T2DM).Methods: Firstly, the active ingredients of SL decoction were sourced from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, with putative targets of active ingredients being predicted using the same database. Secondly, the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were employed to screen the aforementioned targets that act on T2DM, and protein–protein interaction (PPI) networks were constructed in accordance with the results. Thirdly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), which resulted in a comprehensive analysis of the association between SL decoction for the treatment of T2DM and the modulation of intestinal functions. Finally, the effect of the SL decoction on predicted lipopolysaccharide (LPS)‐related targets, as well as intestinal function markers, was validated through in vivo experimentation.Results: A total of 36 active ingredients and 145 potential targets of SL decoction were predicted. GO enrichment analysis indicated that the principal biological processes by which the SL decoction acted against T2DM were responses to LPSs, while KEGG enrichment analysis identified the nuclear factor kappa B (NF‐κB) signaling pathway and toll‐like receptor signaling pathway as the key pathways involved. The in vivo experiments showed that SL decoction improved glycolipid metabolism indexes, inflammatory factor levels, and LPS levels in db/db mice. The immunohistochemical results demonstrated that the SL decoction restored the expression of Occludin, Claudin‐1, and ZO‐1 in the intestine and inhibited the expression of toll‐like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MYD88), and NF‐κB in both the intestine and pancreas. Furthermore, it may influence the levels of short‐chain fatty acids (SCFAs) in feces.Conclusions: This research investigated the multigene pharmacological mechanism of SL decoction against T2DM using network pharmacology and in vivo experiments. SL decoction treatment of T2DM may reverse inflammation by inhibiting LPS‐related pathway activation and improving intestinal function.

Background:Diabetic kidney disease (DKD) is a major global cause of end-stage renal disease. Emerging evidence suggests that hypoxia is a critical factor in the advancement of DKD. Traditional Chinese medicine (TCM) is an effective alternative therapy for DKD. The Qi-Gui-Sheng-Jiang-San (QGSJS) decoction is an effective formula for treating DKD clinically, and its mechanism may be related to regulating hypoxia response, necessitating further investigation and a thorough analysis of the underlying biological mechanisms. Methods:Initially, we employed network pharmacology methods to collect and screen the active constituents of the QGSJS decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and relevant chemical databases. Subsequently, the targets of these active components were predicted via the PubChem and TCMSP databases, while relevant targets associated with DKD were sourced from GeneCards, OMIM, and DrugBank. In the second phase, we built a protein-protein interaction (PPI) network via the STRING database to identify core targets. This was followed by GO and KEGG enrichment analyses to assess if the QGSJS decoction's mechanisms of action are linked to hypoxic response regulation. Finally, in vivo experiments were performed to confirm the findings from the network pharmacology analysis and to comprehensively elucidate the QGSJS decoction's mechanisms of action. Results:The network pharmacology analysis revealed 57 active components in the QGSJS decoction, capable of influencing 72 targets associated with DKD. Quercetin, kaempferol, and isorhamnetin are likely to be the key constituents of the QGSJS decoction. The PPI network suggests that HIF1A serves as a hub gene, closely associated with IL6, NFKBIA, and VEGFA. Enrichment analysis indicates that the QGSJS decoction modulates the HIF-1 signaling pathway and impacts biological processes and molecular functions linked to HIF-1α. In vivo studies demonstrate the QGSJS decoction's renal protective properties, suppressing the expression of HIF-1α, p-STAT3, p-Akt, VEGF, VEGFR, p-NF-κB, and NOTCH1 in the kidneys without affecting PHD2. Conclusion:The QGSJS decoction primarily inhibits HIF-1α through non-oxygen-dependent pathways, mitigating damage related to abnormal hypoxic responses, which may be the main mechanism through which it protects the kidneys.

Background and Objective:The urgent need to identify pathways that can mitigate myocardial ischemia-reperfusion injury (MIRI) has become a central focus in cardiovascular treatment. Chinese herbal medicine (CHM), renowned for its multi-component, multi-channel, and multi-target therapeutic properties, holds significant promise in the management of MIRI. Mitochondria, as pivotal players in MIRI, have been shown to be effectively modulated by CHM through various mechanisms. The objective of this narrative review is to underscore the critical role of mitochondria in MIRI and to provide an up-to-date overview of the latest research advancements in utilizing CHM to treat MIRI by targeting mitochondrial morphology and function. Methods:The PubMed and the China National Knowledge Infrastructure (CNKI) databases were searched using keywords related to MIRI. Relevant English-language articles published from January 2019 to July 2024 were included in this narrative review. Key Content and Findings:Mitochondria are intimately linked to MIRI. The mechanisms involve the regulation of mitochondrial biogenesis and energy metabolism, the functionality of the mitochondrial respiratory chain, resistance to oxidative stress-induced damage, the maintenance of mitochondrial homeostasis, the modulation of calcium ion homeostasis, the preservation of mitochondrial membrane potential, the opening of adenosine triphosphate (ATP)-sensitive potassium channels, and the effective control over the opening of the mitochondrial permeability transition pore, all of which contribute to the balance between autophagy and apoptosis in cardiomyocytes. Various effective monomers of CHM, extracts of CHM, compounds, and proprietary Chinese medicine have demonstrated promising therapeutic potential in basic research, among them, tonic and blood-activating CHMs account for the largest proportion. Conclusions:The prospect of CHM targeting mitochondria for the treatment of MIRI is promising, yet it necessitates overcoming challenges such as low bioavailability and inadequate mechanistic research. By integrating traditional Chinese medicine theories with modern scientific technologies, it is imperative to delve deeper into and optimize the pharmacodynamics, pharmacokinetics, and clinical applications of these herbs.

Metabolic syndrome (Mets) is an important contributor to morbidity and mortality in cardiovascular, liver, neurological, and reproductive diseases. Short-chain fatty acid (SCFA), an organismal energy donor, has recently been demonstrated in an increasing number of studies to be an important molecule in ameliorating immuno-inflammation, an important causative factor of Mets, and to improve lipid distribution, blood glucose, and body weight levels in animal models of Mets. This study reviews recent research advances on SCFA in Mets from an immune-inflammatory perspective, including complications dominated by chronic inflammation, as well as the fact that these findings also contribute to the understanding of the specific mechanisms by which gut flora metabolites contribute to metabolic processes in humans. This review proposes an emerging role for SCFA in the inflammatory Mets, followed by the identification of major ambiguities to further understand the anti-inflammatory potential of this substance in Mets. In addition, this study proposes novel strategies to modulate SCFA for the treatment of Mets that may help to mitigate the prognosis of Mets and its complications.

[This corrects the article DOI: 10.3389/fimmu.2025.1519925.].

Abstract Background Although reperfusion therapy is widely performed in patients with acute myocardial infarction (AMI), the residual risk of poor prognosis remains substantial. As important immune cells involved in the body's inflammatory response, macrophages are differentiated from monocytes that have been recruited to tissues, and their polarisation status has a significant impact on the development and prognosis of AMI. There are no recognised macrophage-associated key regulators that play an important role in the development of AMI. Objective The study aimed to identify potential biomarkers associated with macrophages for the early recognition and intervention of AMI. Methods and results Three datasets which can be obtained publicly (GSE48060, GSE66360, and GSE97320 datasets) from the Gene Expression Omnibus (GEO) database were analysed to identify differentially expressed genes (DEGs) using peripheral blood tissue samples from 83 AMI patients and 74 normal individuals. Subsequent WGCNA analysis was performed and 387 genes with the most significant correlations with macrophages were identified. Then, intersecting 192 DEGs with 387 genes from WGCNA, a total of 151 overlapping genes were found. Protein-protein interaction (PPI) network analysis were performed to identify the hub genes. Further we recruited 44 individuals and colleted blood samples to validate the stability and reliability of the predicted hub tragets toll-like receptor 2 (TLR2), toll-like receptor 2 (TLR4), toll-like receptor 8 (TLR8), matrix metalloproteinase 9 (MMP9) and tyrosine kinase binding protein (TYROBP) using qRT-PCR assay. As a result, TLR2, TLR4, TLR8, MMP9 and TYROBP were identified as the marophage-related biomarkers in AMI. Conclusions The macrophage-related genes TLR2, TLR4, TLR8, MMP9 and TYROBP may enable timely detection of AMI, leading to prompt intervention and better prognosis.

介绍国医大师吕仁和教授运用"六对论治"法治疗膀胱癌术后膀胱灌注化疗尿路刺激征1则验案.吕仁和教授从"六对论治"入手,根据患者的病情缓急选方用药,标本兼顾,思路灵活,总体治法以扶正消癥、活血化瘀止血、清利下焦湿热、健脾益肾法为主,且注重顾护脾胃,虽用药轻巧,但疗效明显,使患者由于膀胱灌注化疗不良反应导致的痛苦症状有了极大缓解,生活质量得到了明显改善.本案体现了吕仁和教授倡导的"健康、长寿"的治疗目标,以及"承古求用,纳新求好"的学术理念.

[目的]基于"六郁"和"郁热"理论探讨糖尿病病机变化,总结国医大师吕仁和教授分期论治糖尿病的经验.[方法]结合"六郁"与"郁热"理论,分析吕老对糖尿病各期病因病机的认识,总结吕老糖尿病分期论治经验,并以临床验案佐证.[结果]吕老将糖尿病分为脾瘅期、消渴期、消瘅期三期,六郁在糖尿病各期均有重要作用.在临床治疗糖尿病时兼顾糖尿病各期病机特点,根据郁滞与热像偏盛,辨证施以解郁、清热之法.所举医案为吕老治疗糖尿病验案,辨证为气血痰热,郁阻血脉,脉络欠活,治法以行气活血、化痰清热为主,疗效确切.[结论]吕老对糖尿病各期病机认识深刻,临床以解郁、清热之法治疗糖尿病,疗效显著,其临床诊疗经验值得参考和学习.

BackgroundTriglyceride-glucose (TyG) index has been reported to be associated with various cardiovascular diseases in recent years. However, the conclusive association between the TyG index and hypertension was not established in the last meta-analysis. Furthermore, it remains unclear whether a linear relationship exists between these two variables.MethodsWe conducted a comprehensive search of the CNKI, VIP, WanFang Data, CBM, PubMed, EMbase, Web of Science, and The Cochrane Library databases up until May 10, 2023, to identify relevant studies conducted in China. We used Stata version 17.0 and Rstudio version 4.2.1 to analyze the data and assess the association between the TyG index and the risk of hypertension, as well as the dose-response relationship between these two variables. We will select either a random-effects model or a fixed-effects model based on the results of the heterogeneity tests and report 95% confidence intervals accordingly.ResultsIn the end, our analysis encompassed 22 studies involving a total of 668,486 participants, comprising 12 cross-sectional studies and 10 cohort studies. Meta-analysis results showed: Analysis of data from China revealed that an elevated TyG index was associated with a higher risk of developing hypertension, as indicated by an OR/HR of 1.36 [95%CI (1.28–1.45) I2 = 69.0% P < 0.001]. Through meta-regression analysis of multiple covariates, we found that study type, study region, sample size, database source, and study quality score, the above five variables were able to explain 63.0% of the total heterogeneity. The results of the dose-response Meta-analysis showed: The TyG index has a linear relationship with the risk of developing hypertension, as indicated by non-significant coefficients of higher-order terms in the nonlinear model (P > 0.05). The linear trend analysis showed that for every one-unit increase in the TyG index, the risk of developing hypertension increased by 1.5 times [1.532 95%CI (1.294, 1.813) P < 0.001]. However, this result is influenced by the number of studies included in the dose-response analysis and requires further corroboration.ConclusionIn the Chinese region, there was an independent association between TyG index and the risk of developing hypertension, with a linear trend. However, the results of the linear trend need to be corrected by the more number of related studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023425836.

Pyroptosis is a type of programmed cell death that induces myocardial ischemia-reperfusion injury (I/RI), which leads to cardiac dysfunction and even lethal reperfusion injury. MiR-122 is a liver-specific miRNA associated with coronary heart disease, but its role in pyroptosis activation in myocardial I/RI remains unclear. Thus, this study aimed to determine whether miR-122 inhibition exerts myocardial I/RI protection in in vivo and in vitro models. An I/RI model was established in vivo using C57BL/J6 male mice. MiR-122 expression was upregulated in the heart tissues from the I/RI group. Quantitative results of echocardiography parameters showed that miR-122 inhibition improved cardiac function and downregulated interleukin (IL)-1β, IL-18, caspase 1, and caspase 11. However, pretransfection with recombinant adeno-associated virus type 9 encoding a DUSP4-specific siRNA (AAV9-siDUSP4) blocked the protective effects of miR-122 inhibition. A hypoxia/reoxygenation (H/R) model was established to mimic the I/R condition in vitro using H9C2 cells. Results showed that miR-122 inhibition increased superoxide dismutase activity (SOD) and cell viability and decreased malondialdehyde (MDA) level, IL-1β, IL-18, caspase 1, caspase 11, and cell death. These protective effects were abolished by transfection with DUSP4-specific siRNA. In summary, miR-122 expression is upregulated in I/RI, and miR-122 inhibition alleviates I/RI by suppressing pyroptosis through targeting DUSP4. Thus, miR-122 may be a novel therapeutic target for treating myocardial I/RI.

情志因素是中医内科学中的常见病因.情志因素既是郁证的主要病因,又是其主要症状.与此同时,情志因素作为伴随症状,又常常在多种中医内科病证中出现,尤其是以神志障碍为主的病证.梳理情志、神志等相关概念内涵,分析情志因素在病证中的几种常见形式,即作为病因、主症以及以神志异常、躯体症状为主症的病证中作为兼症出现.从多角度对相关疾病进行鉴别,与西医学心身疾病、心境障碍、妄想性障碍的概念相互参照,帮助学生进一步深入理解中医情志致病以及以情志为表现病症的具体内涵.

针对糖尿病肾脏病核心病机,重点阐释糖尿病肾脏病"络脉瘀阻""毒损肾络""微型癥瘕""风邪伏络"等创新性理论,综览当代医家有关糖尿病肾脏病辨证方法及其规范化治疗方案研究成果,展示中医药分期辨证治疗糖尿病肾脏病优势.同时,针对糖尿病肾脏病病机理论与辨证规范研究领域存在的问题,提出应该重视古今文献与名老中医经验数据挖掘,重视基于临床流行病学方法的证候学研究,重视科学评价糖尿病肾脏病中医药临床疗效,并建立规范化糖尿病肾脏病分期辨证治疗方案,以期促进糖尿病肾脏病领域中医理论创新与诊治水平提升.

Objective To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis. Methods Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the two drugs and finerenone indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). Results 18 RCTs involving 51,496 patients were included. Finerenone reduced the risk of major adverse cardiovascular events (MACE), renal outcome and hospitalization for heart failure (HHF) (RR [95% CI]; 0.88 [0.80-0.97], 0.86 [0.79-0.93], 0.79 [0.67,0.92], respectively). SGLT-2i were associated with reduced risks of MACE (RR [95% CI]; 0.84 [0.78-0.90]), renal outcome (RR [95% CI]; 0.67 [0.60-0.74], HHF (RR [95% CI]; 0.60 [0.53-0.68]), all-cause death (ACD) (RR [95% CI]; 0.89 [0.81-0.91]) and cardiovascular death (CVD) (RR [95% CI]; 0.86 [0.77-0.96]) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95% CI]; 0.86 [0.78-0.94]). SGLT2i had significant effect in comparison to finerenone (finerenone vs SGLT2i: RR [95% CI]; 1.29 [1.13-1.47], 1.31 [1.07-1.61], respectively) and GLP-1 RA (GLP-1 RA vs SGLT2i: RR [95% CI]; 1.36 [1.16-1.59], 1.49 [1.18-1.89], respectively) in renal outcome and HHF. Conclusions In patients with T2DM and CKD, SGLT2i, GLP-1 RA and finerenone were comparable in MACE, ACD and CVD. SGLT2i significantly decreased the risk of renal events and HHF compared with finerenone and GLP-1 RA. Among GLP-1 RA, GLP-1 analogues showed significant effect in reducing cardiovascular events compared with exendin-4 analogues.

目的:基于Akt/HO-1信号通路探讨芪归升降散对db/db小鼠的肾脏保护机制.方法:选取8周龄雄性自发性2型糖尿病db/db小鼠随机分为模型组、芪归升降散组,另取同源不发病db/m小鼠作为对照组,每组6只,连续灌胃9周后,检测尿微量白蛋白/肌酐比值(ACR)、6 h尿微量白蛋白(6hUTP)水平,血清肌酐(Cr)、尿素氮(BUN)、糖化血清蛋白(GSP)、过氧化氢酶(CAT)、总超氧化物歧化酶(T-SOD)、丙二醛(MDA)水平,观察肾脏病理改变,并检测肾皮质磷酸化蛋白激酶B(p-Akt)、血红素加氧酶-1(HO-1)蛋白表达.结果:与对照组比较,模型组小鼠尿ACR、6hUTP、Cr、BUN、GSP水平显著升高(P＜0.01,P＜0.05),肾脏病理出现肾小球系膜基质增生,肾小管上皮细胞空泡变性、纤维化,明显的炎性浸润,肾组织p-Akt、HO-1信号通路蛋白表达显著升高(P＜0.05,P＜0.01),T-SOD、CAT水平显著降低,MDA水平显著升高(P＜0.01);与模型组比较,芪归升降散组可显著降低尿ACR、6hUTP、Cr、BUN、GSP水平(P＜0.05,P＜0.01),改善肾脏病理,下调肾皮质p-Akt、HO-1信号通路蛋白表达(P＜0.05),升高T-SOD、CAT水平(P＜0.01),降低MDA水平(P＜0.01).结论:芪归升降散可能通过调节Akt/HO-1信号通路,改善炎症与氧化应激,对肾脏起到良好保护作用.

Abstract Background Type 2 diabetes mellitus (T2DM) is a common metabolic disease with significant health, social, and economic consequences. Traditional Chinese medicine (TCM) could effectively regulate blood sugar and influence gut microbiota in T2DM patients. Preliminary studies showed that the Coptis root and ginseng (RG) formula could relieve insulin resistance and prevent the progression of diabetes in mice. Objectives The purpose of this study is to explore the efficacy and safety of RG formula in the treatment of adult patients with T2DM, as well as observing its effects on gut microbiota. Methods and analysis This trial is a randomized, double-blind, placebo-controlled study. A total of 60 participants will be randomized in a 1:1 ratio into an experiment group (RG formula) and a control group (placebo). Patients in both groups will be given diabetes education and basic blood glucose control. Glucose-lowering drugs with significant influence on gut microbiota will be avoided. This trial will last 25 weeks including 1-week run-in, 12-week intervention, and 12-week follow-up visit. The primary outcome is the change in the HbA1c. The secondary outcomes comprise the change in the fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FIL), fasting C-peptide(C-P), insulin resistance index (IRI), inflammatory factors, and species abundance of gut microbiota between the two groups. Safety of medication will also be evaluated. The correlation analysis will be explored between the glycemic indicators, inflammatory factors, and abundance of gut microbiota. Discussion This study will provide the clinical evidence for the efficacy of RG formula in regulating blood sugar and influencing gut microbiota, which will be beneficial to form the integrated therapeutic regimen in T2DM with TCM. Trial registration “Clinical Study on the Intervention of Coptis Root and Ginseng,” Chinese Clinical Trials Registry ChiCTR 2100042126 . Registered on 14 January 2021

吕仁和教授基于对中医经典的深刻认识和丰富的临床经验,于20世纪90年代创造性地提出糖尿病微血管病变"微型瘤瘕"病理假说,对于糖尿病及其并发症的中医诊疗具有重要意义.在该理论指导下,以吕教授为首的研究团队深入开展了系列研究,不仅表明其能有效指导临床,而且从动物、细胞、分子等诸多层面证实了该理论假说的物质基础.在"微型癥瘕"病理假说的影响和启发下,吕教授学术传承人有不少发挥、创造,对拓展中医药原创思维影响深远.

目的:应用网络药理学的研究方法筛选"人参-黄连-三七"药串治疗2型糖尿病胰岛素抵抗合并非酒精性脂肪肝的作用靶点及相关信号通路,通过动物实验明确其疗效与作用机制.方法:通过中药系统药理学数据库与分析平台(TCMSP)检索获取"人参-黄连-三七"的主要化学成分以及相关作用靶点;使用DisGeNET筛选胰岛素抵抗与非酒精性脂肪肝的相关靶标基因;通过韦恩软件筛选出药物与疾病的共同作用靶点;构建"疾病-靶点-成分-药物"网络、蛋白质-蛋白质相互作用(PPI)网络;通过基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析对有效作用靶点进行分析;以db/db小鼠作为动物模型,检测小鼠血糖、胰岛素水平,并通过肝脏HE染色及免疫组织化学法进行进一步的实验验证.结果:通过筛选得到"人参-黄连-三七"药串有效成分39种,有效作用靶点125个,其中作用于胰岛素抵抗与非酒精性脂肪肝的相关靶点27个;分子功能共富集211个条目,生物过程共富集2317个条目,细胞组分共富集105个条目;KEGG通路富集共富集到119条信号通路,其中包括AGE-RAGE信号通路、HIF-1信号通路、PPAR信号通路、PI3 K/AKT信号通路等.通过动物实验验证"人参-黄连-三七"药串水煎剂能够有效降低db/db小鼠血糖,改善胰岛素抵抗,减轻肝脏脂肪变性.与模型组比较,中药组小鼠血糖、胰岛素抵抗指数下降(P<0.05),肝脏NAS评分较模型组明显下降(P<0.05),免疫组织化学染色结果显示,中药组小鼠肝脏PI3K、p-AKT表达水平较模型组明显上升(P<0.05).结论:"人参-黄连-三七"药串能够有效改善db/db小鼠胰岛素抵抗并减轻非酒精性脂肪肝病变,其作用机制可能与调控PI3 K/AKT信号通路有关.