【摘要】 目的:探讨杨桃根2-十二烷基-6-甲氧基-2,5-二烯-1,4-环己二酮(DMDD)对糖尿病小鼠心肌损伤的保护作用及机制。方法:C57BL/6小鼠高糖高脂饲料喂养4周后,腹腔注射小剂量链脲佐菌素复制糖尿病小鼠模型,另设空白组以普通饲料喂养。将造模成功后的小鼠分为模型组和DMDD高(50 mg/kg)、中(25 mg/kg)、低剂量(12.5 mg/kg)组,给予药物治疗8周,检测小鼠空腹血糖(FBG)、血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)水平及心肌组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)含量,苏木精-伊红(HE)染色观察心肌病理变化,天狼星红染色观察心肌胶原纤维增生情况,TUNEL染色观察心肌组织凋亡,实时荧光定量PCR(qPCR)法检测凋亡相关指标Bax、Bcl-2、Caspase-3 m RNA的表达。结果:与空白组比较,模型组小鼠心肌损伤明显,胶原纤维增多,心肌细胞凋亡率明显增加,FBG、LDH、CK、CK-MB、MDA水平显著升高(P<0.01),SOD、GSH含量显著性下降(P<0.01),Bax、Caspase-3 mRNA表达显著上升(P<0.01),Bcl-2mRNA表达显著下调(P<0.01);与模型组相比较,经DMDD治疗后的小鼠心肌损伤减轻,纤维增生减少,心肌细胞凋亡率下降,FBG、LDH、CK、CK-MB、MDA水平显著降低(P<0.05或P<0.01),SOD、GSH含量显著性升高(P<0.05或P<0.01),Bax、Caspase-3 mRNA表达显著下降(P<0.05或P<0.01),Bcl-2 mRNA表达显著上升(P<0.05或P<0.01),且DMDD高剂量组改善作用最明显(P<0.05)。结论:杨桃根DMDD可能通过减轻心肌氧化应激、抑制心肌凋亡,改善糖尿病小鼠心肌损伤。更多还原

【Abstract】 Objective: To investigate the protective effects and possible mechanism of Averrhoa Carambola L.roots DMDD on diabetic myocardial injury in mice. Methods: C57 BL/6 mice were fed high fat food for 4 weeks.The diabetes mellitus model was established by intraperitoneal injection of low dose streptozotocin(STZ). The control group was fed with normal diet. Mice were divided into normal group, model group, metformin group,and DMDD high-, medium-and low-dose groups after modeling. Mice were administrated via gavage for 8 weeks. The levels of fasting blood glucose(FBG), lactate dehydrogenase(LDH), creatine kinase(CK), creatine kinase isoenzyme(CK-MB), malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione(GSH) were detected. HE stainingwas used to observe the histopathological changes of myocardium. Myocardial collagen fibers were stained with Sirius red. TUNEL staining was used to detect the myocardial cells apoptosis. The mRNA expressions of Bax, Bcl-2 and Caspase-3 were detected by qPCR.Results: Compared with the normal group, thelevels of FBG, LDH, CK, CK-MB, MDA, and the m RNA expression of Bax and caspase-3 in the model group were significantly increased, while the m RNA expression of Bcl-2 and the levels of SOD, GSH were significantly decreased(P<0.01). The myocar-dial damage, collagen fiber of myocardial and myocardial cells apoptosis were increased in the model group.Compared with the model group, the levels of FBG, LDH, CK, CK-MB, MDA and the m RNA relative expression of Bax and Caspase-3 in DMDD groups were significantly reduced, whereas the m RNA expression of Bcl-2 and the activities of SOD and GSH were increased(P<0.05 or P<0.01). DMDD ameliorated the myocardial damage, and decreased collagen fiber of myocardial and myocardial cells apoptosis. Conclusion: DMDD attenuates myocardial injury in diabetic mice by reducing oxidative stress and inhibiting myocardial apoptosis.更多还原