Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,m...Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated the expression of myocardial JunB/c-Fos,which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.Conclusion The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK(p38 and ERK1/2)pathway.展开更多
目的基于网络药理学联合基因表达数据库(GEO)芯片分析及分子对接技术探讨健脾清化化瘀汤治疗胃癌前病变(PLGC)的成分靶点及信号通路,预测其潜在作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)及本草组鉴数据库(HERB)搜集健...目的基于网络药理学联合基因表达数据库(GEO)芯片分析及分子对接技术探讨健脾清化化瘀汤治疗胃癌前病变(PLGC)的成分靶点及信号通路,预测其潜在作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)及本草组鉴数据库(HERB)搜集健脾清化化瘀汤中14味药物的活性成分和靶点。通过GEO数据库中的GSE55696基因芯片获取差异表达基因,利用人类孟德尔遗传在线数据库(OMIM)、Dis Ge Net、Gene Cards疾病数据库获取PLGC的相关疾病靶点,运用R软件获取健脾清化化瘀汤治疗PLGC的关键靶点。通过R语言对关键靶点进行基因本体论(GO)和京都基因和基因组的百科全书(KEGG)通路富集分析,利用蛋白互作(STRING)数据库及Cytoscape3.9.1软件绘制关键靶点的蛋白质-蛋白质相互作用(PPI)网络,筛选出核心靶点,利用Cytoscape3.9.1构建健脾清化化瘀汤与PLGC的“活性成分-关键靶点”网络,筛选出核心成分,最后将核心成分与核心靶点进行分子对接,探索蛋白与分子间的亲和性。结果共获得健脾清化化瘀汤226个活性成分,对应416个药物靶点;获得PLGC差异表达基因1673个,疾病数据库获得相关靶点1302个;药物与疾病交集基因149个;GO功能富集分析得到2802个条目,KEGG通路富集分析得到161条相关通路,主要涉及糖尿病并发症晚期糖基化终末产物/AGEs受体(AGE-RAGE)信号通路与癌症相关信号通路;筛选得到核心活性成分槲皮素、木犀草素等,核心靶点TP53、JUN、AKT1等;分子对接结果证实核心成分与核心靶点之间有较好的结合活性。结论健脾清化化瘀汤可能通过参与多条信号通路作用于多成分、多靶点,从而发挥治疗PLGC的效用。展开更多
目的:探讨健脾清化方对初发气阴两虚型2型糖尿病(T2DM)患者的血糖波动、骨骼肌含量及功能的影响。方法:纳入70例初发气阴两虚型T2DM患者,随机分为治疗组和对照组,每组各35例。两组患者均给予生活方式干预,在此基础上,治疗组患者予健脾...目的:探讨健脾清化方对初发气阴两虚型2型糖尿病(T2DM)患者的血糖波动、骨骼肌含量及功能的影响。方法:纳入70例初发气阴两虚型T2DM患者,随机分为治疗组和对照组,每组各35例。两组患者均给予生活方式干预,在此基础上,治疗组患者予健脾清化方口服,对照组患者予安慰剂口服,疗程均为12周。治疗后,评价并比较两组患者的临床疗效;治疗前后,比较两组患者的中医证候总积分,检测患者的血糖在目标范围内时间(TIR)、四肢骨骼肌质量、优势手握力及糖化血红蛋白(HbA1c)、空腹血糖(FBG)、餐后2 h血糖(2 h PBG)水平。结果:研究过程中,治疗组2例患者、对照组1例患者脱落或剔除,最终纳入统计分析者治疗组33例、对照组34例。①治疗后,治疗组的临床总有效率为75.8%,对照组为38.2%,治疗组的疗效优于对照组(P<0.01)。②治疗后,治疗组患者的中医证候总积分较治疗前降低(P<0.05),且治疗组患者的中医证候总积分改善情况优于对照组(P<0.05)。③治疗后,治疗组患者的TIR有上升趋势,但治疗前后差异无统计学意义(P>0.05),对照组患者的TIR显著下降(P<0.05),且治疗组患者的TIR改善情况优于对照组(P<0.05)。④治疗后,治疗组患者的四肢骨骼肌质量及优势手握力均升高(P<0.05),而对照组患者的四肢骨骼肌质量及优势手握力均降低(P<0.05),且治疗组患者的四肢骨骼肌质量及优势手握力改善情况优于对照组(P<0.05)。⑤治疗后,治疗组患者的HbA1c水平降低(P<0.05),且治疗组患者的HbA1c水平改善情况优于对照组(P<0.05)。结论:健脾清化方可改善初发气阴两虚型T2DM患者的血糖波动,提升优势手握力及四肢骨骼肌含量,改善糖代谢及临床症状,其改善血糖波动的机制可能与改善骨骼肌质量和功能有关。展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81874434 and No.81804053)Yangtze River Delta Traditional Chinese Medicine Endocrinology and Metabolic Disease Specialist Alliance(No.ZY2021-2023-0302).
文摘Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated the expression of myocardial JunB/c-Fos,which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.Conclusion The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK(p38 and ERK1/2)pathway.
文摘目的基于网络药理学联合基因表达数据库(GEO)芯片分析及分子对接技术探讨健脾清化化瘀汤治疗胃癌前病变(PLGC)的成分靶点及信号通路,预测其潜在作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)及本草组鉴数据库(HERB)搜集健脾清化化瘀汤中14味药物的活性成分和靶点。通过GEO数据库中的GSE55696基因芯片获取差异表达基因,利用人类孟德尔遗传在线数据库(OMIM)、Dis Ge Net、Gene Cards疾病数据库获取PLGC的相关疾病靶点,运用R软件获取健脾清化化瘀汤治疗PLGC的关键靶点。通过R语言对关键靶点进行基因本体论(GO)和京都基因和基因组的百科全书(KEGG)通路富集分析,利用蛋白互作(STRING)数据库及Cytoscape3.9.1软件绘制关键靶点的蛋白质-蛋白质相互作用(PPI)网络,筛选出核心靶点,利用Cytoscape3.9.1构建健脾清化化瘀汤与PLGC的“活性成分-关键靶点”网络,筛选出核心成分,最后将核心成分与核心靶点进行分子对接,探索蛋白与分子间的亲和性。结果共获得健脾清化化瘀汤226个活性成分,对应416个药物靶点;获得PLGC差异表达基因1673个,疾病数据库获得相关靶点1302个;药物与疾病交集基因149个;GO功能富集分析得到2802个条目,KEGG通路富集分析得到161条相关通路,主要涉及糖尿病并发症晚期糖基化终末产物/AGEs受体(AGE-RAGE)信号通路与癌症相关信号通路;筛选得到核心活性成分槲皮素、木犀草素等,核心靶点TP53、JUN、AKT1等;分子对接结果证实核心成分与核心靶点之间有较好的结合活性。结论健脾清化化瘀汤可能通过参与多条信号通路作用于多成分、多靶点,从而发挥治疗PLGC的效用。
文摘目的:探讨健脾清化方对初发气阴两虚型2型糖尿病(T2DM)患者的血糖波动、骨骼肌含量及功能的影响。方法:纳入70例初发气阴两虚型T2DM患者,随机分为治疗组和对照组,每组各35例。两组患者均给予生活方式干预,在此基础上,治疗组患者予健脾清化方口服,对照组患者予安慰剂口服,疗程均为12周。治疗后,评价并比较两组患者的临床疗效;治疗前后,比较两组患者的中医证候总积分,检测患者的血糖在目标范围内时间(TIR)、四肢骨骼肌质量、优势手握力及糖化血红蛋白(HbA1c)、空腹血糖(FBG)、餐后2 h血糖(2 h PBG)水平。结果:研究过程中,治疗组2例患者、对照组1例患者脱落或剔除,最终纳入统计分析者治疗组33例、对照组34例。①治疗后,治疗组的临床总有效率为75.8%,对照组为38.2%,治疗组的疗效优于对照组(P<0.01)。②治疗后,治疗组患者的中医证候总积分较治疗前降低(P<0.05),且治疗组患者的中医证候总积分改善情况优于对照组(P<0.05)。③治疗后,治疗组患者的TIR有上升趋势,但治疗前后差异无统计学意义(P>0.05),对照组患者的TIR显著下降(P<0.05),且治疗组患者的TIR改善情况优于对照组(P<0.05)。④治疗后,治疗组患者的四肢骨骼肌质量及优势手握力均升高(P<0.05),而对照组患者的四肢骨骼肌质量及优势手握力均降低(P<0.05),且治疗组患者的四肢骨骼肌质量及优势手握力改善情况优于对照组(P<0.05)。⑤治疗后,治疗组患者的HbA1c水平降低(P<0.05),且治疗组患者的HbA1c水平改善情况优于对照组(P<0.05)。结论:健脾清化方可改善初发气阴两虚型T2DM患者的血糖波动,提升优势手握力及四肢骨骼肌含量,改善糖代谢及临床症状,其改善血糖波动的机制可能与改善骨骼肌质量和功能有关。
