基于氧化应激探讨通脉降脂丸对2型糖尿病大血管病变影响的实验研究

Research of impacts of Tongmai Jiangzhi Pills on oxidative stress in Wistar rats with type diabetes mellitus macrovascular complications

目的:观察通脉降脂丸对糖尿病模型大鼠2型糖尿病大血管病变氧化应激的影响。方法:采用对4个月龄雄性Wistar大鼠一次性腹腔注射STZ结合饮水添加Nω-硝基-L-精氨酸甲酯(L-NAME)0.1 mg·m L-1·d-1及高脂饲料喂饲的方法复制2型糖尿病大血管病变模型。成模后大鼠随机分成模型组、阿托伐他汀钙组、通脉降脂丸组,另设15只正常Wistar大鼠为正常对照组。给药时间30 d。实验结束后测定大鼠血检测血清F2-异前列烷、血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MAD)、总抗氧化能力(T-AOC)等活性水平;检测醛糖还原酶AR、NADPH氧化酶亚基的活性;RT-PCR法测定主动脉NADPH氧化酶亚基p22phox m RNA及p47phox m RNA表达。结果:通脉降脂丸组大鼠血清SOD、GSH-Px、T-AOC等活性较模型组升高(P<0.05),阿托伐他汀和通脉降脂丸均能降低主动脉p47phox m RNA、p22phox m RNA的表达水平(P<0.05)。结论:通脉降脂丸可提高糖尿病GK大鼠血清SOD、GSH-Px、T-AOC活性,下调主动脉p47phox m RNA、p22phox m RNA表达,可能因此减轻糖尿病大血管病变机体的氧化应激水平,这可能是通脉降脂丸治疗T2DM大血管病变的可能机制之一。

Objective： To study the effect of Tongmai Jiangzhi pill（TMJZ） on the oxidative stress in Wistar rats with T2 DM Macroangiopathy. Methods： 4-month-old male Wistar rats considered for the experiment and they were given intraperitoneal injection of STZ and Nω-nitro-L-arginine methyl ester（L-NAME） added into the drinking water plus high fat diet to prepare rats model with diabetic vascular disease. Wistar rats were divided into model group, atorvastatin group, TMJZ group and another 15 Wistar rats act as the normal group. After 30 days of treatment, Antioxidant enzymes was examined with colorimetry while the m RNA expression of p22 phox and p47 phox in thoracic aorta vessel wall were measured by real-time PCR. Results： The TMJZ group had significantly higher activity of SOD, GSH-Px and T-AOC compared with model group, and higher activity of both SOD and GSH-Px compared with atorvastatin group. Compared with model group, the m RNA expression of p47 phox and p22 phox decreased in atorvastatin group and TMJZ group. Conclusion： Tongmai Jiangzhi pill can improve the activities of antioxidant enzymes（including SOD, GSH-Px and T-AOC） and significantly reduce the m RNA expression of p47 phox and p22 phox in aorta in Wistar rats with T2 DM. So, Macroangiopathy by Tongmai Jiangzhi pill maybe one of the possible curing mechanisms that inhibit the oxidative stress and prevents T2 DM in human body also.