虎杖苷对小鼠糖尿病心肌肥厚保护作用及机制研究.docVIP

虎杖苷对小鼠糖尿病心肌肥厚保护作用及机制研究 　　[摘要] 观察虎杖苷（PD）对小鼠糖尿病心肌肥厚的保护作用，并探讨其可能机制。利用小剂量STZ连续5 d腹腔注射建立小鼠糖尿病模型，以心肌肥厚指数（LVHI，左心室/右心室+室间隔）、左心室/体重（LV/BW）、组织学检查和心房利钠因子（ANF）mRNA表达为心肌肥厚指标；监测空腹血糖值（FBG），并检测血清胰岛素含量、血浆糖化血红蛋白（HbA1c）水平，计算胰岛素抵抗指数（HOME.IR）；分别用qRT-PCR和Western blot方法检测mRNA及蛋白表达。结果显示，模型组小鼠FBG持续超过11.1 mol?L-1，BW明显降低，胰岛素含量、HbA1c和HOME.IR明显升高，提示糖尿病模型建立且保持稳定；糖尿病小鼠LVHI，LV/BW及ANF mRNA均增加，细胞表面积增大，提示小鼠出现心肌肥厚。同时，模型组PPARβ mRNA和蛋白表达降低，NF-κB p65，COX-2及iNOS表达则明显增加。给予PD（50，100 mg?kg-1?d-1）治疗后，糖尿病小鼠BW增加，FBG，胰岛素及HbA1c含量降低，胰岛素抵抗改善，心肌肥厚指标亦明显好转，提示PD具有保护糖尿病心肌肥厚的作用。同时，PD使PPARβ的表达上调，并抑制NF-κB p65，COX-2及iNOS的表达，提示PD的保护作用可能与其激活PPARβ，抑制NF-κB及COX-2，iNOS信号通路有关。 　　[关键词] 虎杖苷；糖尿病心肌肥厚；PPARβ；NF-κB；COX-2；iNOS 　　[Abstract] To observe the preventive effect of polydatin on diabetic myocardial hypertrophy in mice and discuss its and mechanism. The diabetic model was induced with low dose STZ （40 mg?kg-1?d-1×5 d， ip） for five days in mice. The myocardial hypertrophy was determined by hypertrophy indexes （LVHI， left ventricular/right ventricle and septum）， left ventricular/body weight （LV/BW）， the histological examination and the mRNA expression of atrial natriuretic factor（ANF）. The fast blood glucose（FBG）， serum insulin and plasma hemoglobin A1c（HbA1c） levels were detected， and then HOMA insulin resistance index（HOMA.IR） was calculated. The mRNA and protein expressions were measured by qRT-PCR and western blotting， respectively. According to the results， the FBG of the model group exceeded 11.1 mol?L-1， with notable decrease in BW and significant increase in insulin， HbA1c and HOME.IR， suggesting the successful establishment and stability of the diabetic model. The increases in LVHI， LV/BW， cell surface and ANF mRNA indicated a myocardial hypertrophy in diabetic mice. Meanwhile， the model group showed decrease in mRNA and protein expressions of PPARβ and significant increase in NF-κB p65， COX-2 and iNOS expressions. After the preventation with PD （50， 100 mg?kg-1?d-1）， diabetic mice showed increase in BW， reduction in t