Objective This study aims to evaluate the renoprotective effects of QGDD in a DKD model exhibiting metabolic memory features and to explore its potential mechanism involving the regulation of ferroptosis via the SIRT1/Nrf2 signaling pathway.Methods A DKD rat model was induced using streptozotocin (STZ). The rats were assigned to the Blank Control Group (C), Model Group (M), Metformin group (Met), and low-, medium-, and high-dose QGDD groups (QGDD-L/M/H). Intervention effects were assessed by monitoring body weight, fasting blood glucose, renal function markers (24-UTP, BUN, Scr, Cys-C, β2-MG), renal histopathology (HE/Masson staining), oxidative stress markers (Fe2+, MDA, GSH, SOD), cell death indicators (TUNEL, ROS), and expression of genes and proteins associated with the SIRT1/Nrf2 pathway (RT-qPCR, Western blot).Results All QGDD dose groups decreased 24-hour urinary protein excretion and serum levels of BUN, Scr, Cys-C, and β2-MG. The medium-dose QGDD group notably reduced renal Fe2+ and MDA levels, increased GSH and SOD activity, and inhibited ROS accumulation and cellular apoptosis. QGDD activated the SIRT1/Nrf2 pathway, significantly upregulating the mRNA and protein expression of Nrf2, HO-1, and GPX4, while suppressing the accumulation of AGEs and Ferritin.Conclusion QGDD mitigated the persistent elevation of AGEs, a hallmark of metabolic memory in DKD by activating the SIRT1/Nrf2 signaling pathway to inhibit ferroptosis-associated lipid peroxidation and oxidative stress. Its multi-target synergistic effects provide a solid experimental foundation for the use of Chinese herbal formulations in treating DKD. The medium-dose group demonstrated optimal therapeutic efficacy, emphasizing the significance of dose optimization.
Diabetic nephropathy (DN) is the most common complication of diabetes, with immune-mediated inflammation playing a significant role in its pathophysiology. The complement system, a key proinflammatory factor, is implicated in DN. This study was aimed at identifying diagnostic biomarkers related to the complement system in DN using bioinformatics methods. We analyzed three datasets (GSE96804, GSE104948, and GSE1009) from public databases, employing differential expression analysis and machine learning to identify complement system-related genes (CSRGs) as potential biomarkers. A diagnostic nomogram was constructed based on these genes, and immune microenvironment differences between the DN and control groups were explored. Gene interaction networks, enrichment analysis, and drug predictions were also conducted. Mendelian randomization (MR) was used to examine the causal links between identified biomarkers and DN. Our analysis identified five biomarkers (CKB, ANXA1, HSPA1L, CYP27B1, and XYLT1) associated with DN. A diagnostic nomogram based on these biomarkers showed high accuracy (model correction slope close to 1 and AUC close to 1). Immune infiltration analysis revealed significant differences in immune cell subsets between the DN and control groups. Gene set variation analysis (GSVA) indicated that the oxidative phosphorylation (OXPHOS) pathway was activated in CKB, HSPA1L, CYP27B1, and XYLT1 while inhibited in ANXA1. MR confirmed HSPA1L as a risk factor for DN (OR = 1.625, 95% CI: 1.272-2.076, p = 9.96e - 05). In conclusion, these five CSRGs may play significant roles in DN progression, providing a foundation for further research into DN pathogenesis and potential molecular markers for clinical diagnosis.
This study aims to investigate the mechanism of Buyang Huanwu Decoction and Didang Decoction regulating activating transcription factor 6(ATF6)/thioredoxin domain containing 5(TXNDC5) signaling axis to mediate macrophage-myofibroblast transformation(MMT) pathway in chronic kidney disease. Twenty-four SPF SD rats were randomly divided into a blank group(n=9) and a modeling group(n=15). The chronic kidney disease model was established by gavage of adenine for 28 days. After successful modeling, the modeling group was randomly divided into a model group and a Buyang Huanwu Decoction and Didang Decoction group. The blank group and the model group were treated with the same volume of physiological saline, and the Buyang Huanwu Decoction and Didang Decoction group was treated by gavage of Buyang Huanwu Decoction and Didang Decoction(13.8 g·kg~(-1)) daily for 28 days. The 24 h urine was collected on the 28th and 56th days of the experiment, and the 24 h urine protein content was detected. After the last administration, all rats were weighed and anesthetized. The kidney weight of the rats was measured, and the renal index was evaluated. The content of serum creatinine(Scr) and blood urea nitrogen(BUN) was detected by an automatic biochemical analyzer, and the concentrations of serum interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and arginase-1(Arg-1) were detected by enzyme-linked immunosorbent assay. The pathological changes of renal tissue were observed by hematoxylin-eosin staining and Masson staining, and the collagen volume fraction(CVF) was calculated. Transmission electron microscopy(TEM) was used to observe the ultrastructural changes of mitochondria in rat renal tissue cells. Multiplex immunofluorescence was used to detect the co-localization of cluster of differentiation 68(CD68)~+α-smooth muscle actin(α-SMA)~+ and CD68~+α-SMA~+collagen type Ⅰ(COL-Ⅰ)~+ in the kidney. Moreover, real-time quantitative polymerase chain reaction was utilized to quantify the mRNA levels of ATF6, TXNDC5, transforming growth factor-β1(TGF-β1), and α-SMA in renal tissue, and the protein levels of ATF6, TXNDC5, and TGF-β1 in the renal tissue were determined by Western blot. The results showed that compared with the blank group, the model group showed a significantly decreased body weight and significantly increased 24 h urine protein, kidney weight, and renal index. The serum levels of Scr, BUN, IL-1β, and TNF-α were significantly increased, while the serum levels of IL-10 and Arg-1 were significantly decreased. Furthermore, the pathological changes of renal tissue were severe, and CVF was significantly increased. The mitochondrial structure of kidney tissue was disordered. High expression of CD68~+α-SMA~+ cells was found in renal tissue, and CD68~+α-SMA~+ MMT cells significantly co-expressed COL-Ⅰ. Finally, the expression of α-SMA mRNA in renal tissue was significantly increased, and the mRNA and protein expression levels of ATF6, TXNDC5, and TGF-β1 in renal tissue were significantly increased. Buyang Huanwu Decoction and Didang Decoction significantly increased the body weight and the levels of IL-10 and Arg-1 in the serum of chronic kidney disease rats and significantly decreased the content of 24 h urine protein, kidney weight, renal index, and the serum levels of Scr, BUN, IL-1β, and TNF-α. The pathological damage of renal tissue was significantly improved, and the CVF was significantly decreased. The ultrastructural damage of renal tissue was significantly improved, as evidenced by TEM. Moreover, Buyang Huanwu Decoction and Didang Decoction decreased the expression of CD68~+α-SMA~+ and CD68~+α-SMA~+COL-Ⅰ~+ in renal tissue and down-regulated the expression level of α-SMA mRNA and the mRNA and protein levels of ATF6, TXNDC5, and TGF-β1 in renal tissue. In conclusion, Buyang Huanwu Decoction and Didang Decoction can regulate ATF6/TXNDC5 signaling pathway, down-regulate TGF-β1 expression, reduce the occurrence of MMT in chronic kidney disease, reduce renal fibrosis, and improve renal injury, so as to play a protective role in kidney.
Background Xiezhuo Huayu Yiqi Tongluo Formula (XHYTF) consists of 14 Chinese herbal medicines. In this study, we investigated the potential mechanism of XHYTF in the treatment of uric acid nephropathy (UAN) through network pharmacology, molecular docking, and in vivo methods. Methods Using various pharmacological databases and analysis platforms, information on the active ingredients and targets of Chinese herbal medicine was collected, and UAN disease targets were retrieved using OMIM, Gene Cards, and NCBI. Then common target proteins were integrated. A Drug-Component-Target (D-C-T) map was constructed to screen core compounds and build a protein-protein interaction (PPI) network. Further, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for common targets, and a Drug-Component-Target-Pathway (D-C-T-P) network diagram was constructed. The molecular docking simulation was performed to verify the binding affinity between core components and hub targets. Subsequently, the UAN rat model was established, followed by the collection of serum and renal tissues. The expression levels of indicators in the serum were determined using an enzyme-linked immunosorbent assay. The pathological changes of renal tissues were detected using H & E staining and Masson staining. The expression of related proteins in renal tissue was detected by western blot. Results In the study, 216 active ingredients and 439 targets in XHYTF were screened, and 868 targets were identified as being related to UAN. Among them, 115 were common targets. Based on the D-C-T network, quercetin, luteolin, β-sitosterol, and stigmasterol were observed to be the key active ingredients of XHYTF that were effective against UAN. The analysis of the PPI network revealed TNF, IL6, AKT1, PPARG, and IL1β as the 5 key targets. GO enrichment analysis revealed that the pathways were mainly concentrated in cell killing, regulation of signaling receptor activity, and other activities. Subsequently, KEGG pathway analysis revealed that multiple signaling pathways, including the HIF-1, PI3K-Akt, IL-17, and other signaling pathways, were closely related to the action of XHYTF. All 5 key targets were confirmed to interact with all core active ingredients. In vivo experiments indicated that XHYTF significantly reduced blood uric acid and creatinine levels, alleviated inflammatory cell infiltration in kidney tissues, reduced the levels of serum inflammatory factors such as TNF-α and IL1β, and ameliorated renal fibrosis in rats with UAN. Finally, western blot revealed decreased levels of PI3K and AKT1 proteins in the kidney, which confirmed the hypothesis. Conclusion Collectively, our observations demonstrated that XHYTF significantly protects kidney function, including alleviation of inflammation and renal fibrosis via multiple pathways. This study provided novel insights into the treatment of UAN using traditional Chinese medicines.
伴随明清时期温病学派的兴起,三焦辨证理论的发展亦日趋成熟,以“温病四大家”为代表,其中叶天士提出三焦辨治温病,薛生白提出湿热病中的三焦传变,吴鞠通以三焦辨证为纲创立三焦辨证之先河,王孟英总结前人成果不断完善三焦辨证体系,三焦辨证体系由此不断完善。本文着重从吴氏三焦辨证学说的角度出发,结合吴鞠通的三焦辨证学说,从三焦辨病位、三焦辨传变途径、三焦运用于临床这三个方面对其应用规律进行了深入的剖析,以期将其更好的应用于临床。
目的 探讨基于数据挖掘《临证指南医案》中叶天士治疗痞满的组方特点及用药规律.方法 通过研究《临证指南医案》中"痞""痞塞""月真胀"等病案中涉及药方,并对其中的用药进行筛选、规范,利用Excel及中医传承辅助平台(V2.5)进行数据统计,分析药物使用频次、聚类分析等.结果 《临证指南医案》中共80例(初诊71例,复诊9例,处方89个)中涉及"痞满"病证的医案,共使用中药118味,总频次为627次;频次≥10次的中药有18味,使用频次占总频次的56.78%(356/627);药性以辛、温为主;归经以脾、肺、胃经为主;药物分类以止咳化痰平喘药居多,理气药、利水渗湿药次之;聚类分析核心药物组合14个,新处方组合5个.结论 《临证指南医案》治疗痞满是根据证型用药,如脾胃亏虚:补虚药、温里药;肝胃不和:理气药、补虚药;痰湿中阻:利水渗湿药、化湿药;湿热阻胃:化痰止咳平喘药、清热药.
伴随明清时期温病学派的兴起,三焦辨证理论的发展也趋于成熟,以叶天士、薛生白、吴鞠通、王孟英为代表的四位医家被后人誉为"温病四大家".四大家关于温病三焦辨证方面的成就可概括为:叶天士提倡并运用三焦作为辨证纲领治疗温病;薛生白创新性提出湿热病的三焦辨证;吴鞠通创立三焦辨证理论;王孟英"以轩岐仲景之文为经,叶薛诸家之辨为纬",对温病学理论全面系统整理的同时,创新性补充并完善三焦辨证的内容.现以温病四大家关于三焦辨证的学术思想作为研究对象,旨在分析温病四大家运用三焦辨证的规律.
The pathogenesis, clinical manifestations and pathological changes of diabetes nephropathy(DN) are related to the collateral disease theory of traditional Chinese medicine. In recent years, treatment and study of DN based on collateral diseases theory has gradually become a trend. Combined with literature, clinical experience and fundamental research, it is summarized that the core pathogenesis of DN is deficiency and stasis of collateral, the treatment method is to tonify deficiency for removing obstruction. It is believed that qi and blood should be taken as the key points in tonifying deficiency, and the difference between unblocking collaterals and removing blood stasis should be emphasized. The prescriptions should attach importance to strengthening healthy energy and Xinrun Tongluo herbs, and pay attention to slow attack and smooth collaterals. This paper expounds the pathogenesis and progress of DN from the theory of ‘collateral invasion in chronic sickness’, and discusses the current situation and thinking of treating DN from collaterals, with a view to providing reference for the prevention and treatment of DN.
目的:探究《临证指南医案》胁痛病篇组方用药规律及其学术思想.方法:整理《临证指南医案》胁痛病篇中的处方,通过中医传承计算平台(TCMICS)V3.0软件对所整理的方剂进行分析.结果:共整理出28首方剂,73味中药,总用药频次192次;四气中以温、平、寒为主;五味中以苦、甘、辛为主;归经以肝经为主,其次为脾经和心经;药物功效以补虚类、活血化瘀类为主,其次为理气类和清热类;用药频次排名居前10位的药物为当归、桃仁、柏子仁、牡丹皮、半夏、茯苓、陈皮、地黄、川楝子、阿胶;药物组合频次在5次及以上的有8组;将整理后的73味中药聚类分析后得出3类新处方.结论:《临证指南医案》治疗胁痛病用药主要围绕着"滋阴柔肝""活血化瘀""疏肝健脾""清热利湿"展开,为胁痛的临床治疗用药提供新的指导.
紫苏入药最早载于《名医别录》,被列为中品,其叶、梗、子分别以(紫)苏叶、(紫)苏梗、(紫)苏子命名入药,临床上应用广泛.从法象思维出发,通过分析紫苏体、色、气、味、形的所成之时、所生之地等形和象,寻求对紫苏的"药象"理解,辨析其"药象"机理,并结合历代中医本草论著的相关条文,领悟紫苏的四气、五味、升降浮沉、功效等"法象"之理,以中医独特思维模式解读紫苏,为本草学研究和临床实践提供参考.
叶天士在《临证指南医案》对五苓散加减变通,或与其它方剂合用,对多种疾病疗效显著.本文将五苓散医案涉及的篇目、症状进行数据分析,并对部分医案进行浅析与探索,领会叶天士运用五苓散的学术思想,以期对临床应用五苓散有所裨益.
目的 基于中医传承辅助系统,探讨吴鞠通《温病条辨》的养阴方剂用药经验.方法 将《温病条辨》中关于三焦养阴论治方药,写入Excel软件中并复查,采用Excel软件进行常用药物频次等相关信息的统计分析.中医传承辅助系统对方药进行方剂规律分析.结果 筛选《温病条辨》治疗温病养阴的方剂29首,使用药物22味,总频次112次.上焦养阴方剂7首;中焦养阴方剂10首;下焦养阴方剂12首.高频三焦养阴方剂:加减复脉汤、五汁饮、清宫汤、清营汤、增液汤等.常用三焦养阴药物是:麦冬、生地黄、阿胶等.高频养阴药物功效:补虚药、清热药、解表药、平肝息风药等.养阴药物药性以寒性为主,药味以甘苦为主.结论 通过挖掘《温病条辨》中29首养阴方剂,从多角度分析得出吴鞠通治温热病善于从三焦辨证,强调润肺化气,重视脾胃,以清热生津、健脾益气、宣化肺气,清营凉血为治疗原则.
文章结合明代瘟疫流行的历史背景,从《温疫论》原文出发,根据达原饮的立法和运用思路及温疫学派相关论述,认为达原饮为邪在膜原而设,治疗“以逐秽为第一要义”.湿热秽浊盘踞膜原具有多重隐匿性,瘟疫伏邪理论和逐邪法可为应对现今新发传染性疾病的中医病因病机及治疗方法提供参考思路.
《温病条辨》是温病学派的重要著作之一,吴鞠通在前人基础上创造性提出"三焦辨证"理论.该理论是吴鞠通在三焦学说的基础上总结出的一套指导温病演变规律的辨证理论体系.它提出了温病发生发展的部位、症候特点、病机演变及传变规律等.三焦辨证理论与卫气营血辨证、脏腑辨证、气血津液辨证、六经辨证等中医辨证理论体系密切相关,相辅相成,互为补充.该文梳理了《温病条辨》中三焦辨证有关内容,整理吴鞠通三焦辨治的基本思路,探求三焦辨证在温病中的规律,旨在更好地服务临床,提高临床疗效.
目的:探讨加味宣痹汤治疗急性痛风性关节炎(AGA)的效果及相关作用机制.方法:采用高尿酸血症(HUA)联合AGA的造模方法,以加味宣痹汤对照秋水仙碱作为干预手段.评测干预后各组大鼠左踝关节炎症指数、足肿胀情况;并在取材后,观察大鼠左踝关节滑膜组织形态学炎性病理情况,检测血清中尿酸(SUA)、C-反应蛋白(CRP)、白细胞介素-1β (IL-1β)、肿瘤坏死因子-α(TNF-α)浓度,以及左踝关节液中TLR4、MyD88、IRAK4 mRNA表达水平.结果:治疗4次后,加味宣痹汤各剂量组大鼠炎症指数、足肿胀水平均显著低于模型组(P<0.05).与模型组比较,加味宣痹汤各剂量组大鼠血清SUA、CRP、IL-1β、TNF-α水平和关节液TLR4、MyD88、IRAK4 mRNA表达水平显著降低(P<0.05),且加味宣痹汤中、高剂量组大鼠上述指标均低于秋水仙碱组(P<0.05).HE染色病理切片显示,秋水仙碱组和加味宣痹汤各剂量组大鼠踝关节滑膜组织中炎性细胞数量和血管充血现象明显较少,其中高剂量组与正常组最接近.结论:加味宣痹汤对HUA合并AGA大鼠具有一定的抗炎、消肿、降尿酸作用,其可能是通过抑制TLR4、MyD88、IRAK4的活化,使TNF-α、IL-1β等炎症因子减少释放,从而发挥作用.
芳香药在新型冠状病毒肺炎(新冠肺炎)防治中的重要作用包括:① 芳香药具有辛香开散、善于走窜的特性,能够疏通气机,燥化湿邪,符合新冠肺炎的核心病机,即以湿邪为核心致病因素,以呼吸道症状为主要表现;② 新冠肺炎重症患者中超过六成出现"谵妄症",乃湿邪蒙蔽心包所致,芳香药化湿醒神开窍,可用于治疗新冠肺炎窍闭神昏诸症;③ 芳香药可以避秽防疫,增强人体正气,各省市发布的治疗新冠肺炎诊治方案的处方中大量运用了芳香药,可见芳香药在此次疫病防治中的作用不可或缺.现代药理学研究也进一步证实了芳香药避秽防疫的机理,即通过抑制病毒、细菌的活力,阻断病毒结合位点,提高机体免疫力,从而发挥防病治病的作用."预饮芳香正气药,则邪不能入",应将芳香药大量运用于新冠肺炎的防治中.
笔者以叶天士络病理论为指导,通过研究《临证指南医案》中胁痛案,探讨胁痛络病的病因病机和辨证论治,总结归纳叶天士辨治胁痛的选方用药规律.叶天士认为胁痛络病的辨证可分虚实,络实证分为肝络气滞、痰湿阻络、寒凝阻络和血络瘀痹证;络虚证分为营络虚寒和肝肾亏虚证.治疗上,叶天士提出"络以辛为泄"的观点,首创辛味通络法.胁痛络实证宜攻之,以通络为法;胁痛络虚证,以"大凡络虚,通补最宜"为法,治以补虚通络,常用益气补血和甘缓柔润之品来荣养脉络.叶天士认为胁痛初起病在气分,肝失疏泄,气机失于调达,肝气郁滞则发胁痛;胁痛日久入血络,肝经气血郁滞,气滞血瘀,瘀血阻滞经脉,同时精血亏虚,络脉失于温润荣养而痛;且久病可入肝络,血瘀气滞,肝络气机运行不畅,肝失疏泄,亦致胁痛.叶天士善以柔肝来通络,盖肝为刚脏,多用甘缓养血柔润之品以益肝体,既能养血柔肝,又能辛润通络,使其用条达和畅.
新型冠状病毒肺炎属于中医学"瘟疫"范畴,病因为感受"疫戾"之气,病性有寒、湿、热、毒、虚之分.根据大多患者具有低热、脘痞、肢倦乏力、便溏、苔白腻等证候表现,该病与"湿"邪关系密切.全国各省市中医诊疗方案亦提示湿邪为患为本次新冠肺炎病机的基本特点.湿性重浊、黏腻,起病隐匿,可蒙上流下,病变早期多在太阴、阳明,其后可窜及少阳,内陷厥阴,甚则内闭外脱.湿邪为患,病势缠绵,病情复杂多变,临床诊治较为棘手.湿邪对瘟疫发生、发展及传变可推波助澜,使瘟疫复杂多变.从"湿"邪在瘟疫中的发病作用着手,探讨新冠肺炎的中医辨治,分析新发传染病发病及传变特点,以期运用瘟疫理论完善中医防治方案,更好指导临床实践.
本文从三焦辨证理论探讨癌性发热的病因病机,认为其病机为气血阴阳亏虚为本,三焦气化功能失常,气血津液代谢紊乱,导致湿、毒、痰、瘀内生,久蕴化热,有虚实不同病理.辨证可分为上焦火盛、中焦气虚、湿热,下焦阴虚、阳虚,以三焦分治,分别予清热解毒、益气升阳、清热利湿、滋阴潜阳等.