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作 者:姜欣[1] 王智[1] 王娟[2] JIANG Xin;WANG Zhi;WANG Juan(Department of Cardiology,The Hospital Affiliated to Beihua University,Jilin 132001,China;Department of Gynecology,Jilin Central Hospital,Jilin 132001,China)
机构地区:[1]北华大学附属医院心血管科,吉林吉林132001 [2]吉林市中心医院妇科,吉林吉林132001
出 处:《中成药》2024年第2期444-450,共7页Chinese Traditional Patent Medicine
基 金:吉林省中医药管理局科技项目(2019126)。
摘 要:目的 探讨金雀异黄素减轻糖尿病大鼠心肌纤维化的作用及潜在机制。方法 通过高脂饮食结合腹腔注射链脲菌素(STZ)法建立大鼠2型糖尿病(T2DM)模型,并随机分为模型组、二甲双胍组(100 mg/kg)及金雀异黄素低、高剂量组(50、100 mg/kg),另设正常组给予常规饮食,每组10只。各给药组灌胃给药8周,检测体质量、心功能、心脏质量及心脏指数,血清CK-MB、AST及LDH活性,观察心肌纤维化程度,心肌组织转化生长因子-β1(TGF-β1)、Smad同源物3(Smad3)mRNA和蛋白表达,心肌组织Ⅰ型胶原(CollagenⅠ)和Ⅲ型胶原(CollagenⅢ)蛋白分布及表达。结果 与模型组比较,金雀异黄素各剂量组大鼠体质量、每搏输出量(SV)及射血分数(EF)升高(P<0.01),心脏指数、左心室收缩末期内径(LVIDs)、血清肌酸激酶同工酶(CK-MB)、天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)活性降低(P<0.05,P<0.01),心肌组织胶原相对面积及CollagenⅠ、CollagenⅢ蛋白表达均降低(P<0.05,P<0.01),心肌组织TGF-β1、Smad3 mRNA和蛋白表达降低(P<0.05,P<0.01),金雀异黄素高剂量组左心室舒张末期内径(LVIDd)降低(P<0.05)。结论 金雀异黄素可通过抑制TGF-β1/Smad3信号通路,减轻2型糖尿病大鼠心肌纤维化作用,进而发挥保护心脏效应。AIM To explore the effects of genistein on reducing myocardial fibrosis in diabetic rats and the possible mechanism.METHODS The rat models of type 2 diabetes mellitus(T2DM)established by high-fat diet feeding and intraperitoneal streptozotocin(STZ)injection were randomly divided into the model group,the metformin group(100 mg/kg)and the low-dose and high-dose genistein groups(50,100 mg/kg),in contrast to those of the normal group given normal diet,with 10 rats in each group.After 8 weeks gavage of the corresponding drugs,the rats had detections of their weight of the body and the heart,the heart function,levels of the cardiac indices,the biomarkers of serum creatine kinase isoenzyme(CK-MB),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH)activities,the extent of myocardial fibrosis,myocardial mRNA and protein expressions of transforming growth factor-β1(TGF-β1)and Smad homologue 3(Smad 3),and the myocardial distribution and expressions of CollagenⅠand CollagenⅢ.RESULTS Compared with the model group,the genistein groups shared increased body weight,stroke output(SV)and ejection fraction(EF)(P<0.01);decreased levels of cardiac indices,left ventricular internal diameter end systole(LVIDs),CK-MB,AST and LDH activities(P<0.05,P<0.01);decreased relative area and myocardial expressions of CollagenⅠand CollagenⅢ(P<0.05,P<0.01);and decreased myocardial expressions of TGF-β1 and Smad3 mRNA and protein(P<0.05,P<0.01).Additionally,the high-dose genistein group was observed with decreased level of left ventricular internal diameter end-diastole(LVIDd)(P<0.05).CONCLUSION Genistein can protect the hearts of T2DM rat models by reducing their myocardial fibrosis via TGF-β1/Smad3 signaling pathway.
关 键 词:金雀异黄素 糖尿病 心肌纤维化 TGF-β1/Smad3信号通路
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