N-乙酰半胱氨酸对糖尿病大鼠心肌损伤的保护作用

目的探讨N-乙酰半胱氨酸对糖尿病心肌病大鼠心肌损伤的保护作用及机制。方法用链脲佐菌素建立糖尿病模型,50只雄性SD大鼠随机分为5组:正常组、糖尿病组、N-乙酰半胱氨酸低、中及高剂量组,N-乙酰半胱氨酸低、中及高剂量组分别按50、100及200 mg/(kg·d)灌胃12周。测定大鼠心功能、心脏质量指数及左心室质量指数、血清和左心室心肌组织中超氧化物歧化酶及谷胱甘肽过氧化物酶的活力;Masson染色观察形态学变化及测量心肌胶原容积分数;免疫组织化学法检测转化生长因子β1、SMAD3、SMAD7的蛋白表达水平。结果与正常组相比,糖尿病组大鼠左心室舒张期末压显著升高,左心室收缩压和±dp/dtmax显著降低,心脏质量指数及左心室质量指数明显增高,超氧化物歧化酶和谷胱甘肽过氧化物酶活力明显下降,心肌胶原容积分数明显升高,转化生长因子β1和SMAD3蛋白的表达增加,SMAD7蛋白的表达减少(P均<0.01)。与糖尿病组相比,N-乙酰半胱氨酸各剂量组灌胃12周后以上指标均得到改善,以高剂量组改善最为明显(P<0.01)。结论 N-乙酰半胱氨酸对糖尿病心肌有保护作用,其机制可能与抑制氧化应激,下调转化生长因子β1、SMAD3表达及上调SMAD7表达有关。

Protective Effect of N-acetylcysteine on Myocardial Injury in Diabetic Rats

Aim To investigate the protective effects and mechanism of N-acetylcysteine(NAC) on myocardial injury in diabetic rats. Methods The diabetic model was established with streptozotocin(STZ).The fifty male SD rats were randomly divided into five groups: the normal group,the diabetic group,the low,middle and high dose N-acetylcysteine treatment group.N-acetylcysteine of 50,100 and 200 mg/kg was respectively given to the low,middle and high dose drug treatment groups by gavage 12 weeks.Rats’ heart function,body weight(BW),heart weight(HW) and left heart weight(LHW) were tested,HW/BW and LHW/BW were calculated,the activities of SOD and GSH-PX in serum and myocardial tissue were measured.Morphological change was observed and myocardial collagen volume fraction was measured by Masson staining.The protein expression levels of TGF-β1,SMAD3 and SMAD7 were determined by immunohistochemistry. Results Compared with the control group,LVEDP of the diabetic group was significantly increased(P<0.01) and LVSP,±dp/dtmax were significantly reduced(P<0.01).All the cardiac mass index and left ventricular mass index were higher(P<0.01).The activities of SOD and GSH-PX were significantly reduced(P<0.01).The levels of TGF-β1 and SMAD3 were significantly up-regulated(P<0.01),the level of SMAD7 was declined significantly(P<0.01).Compared with the diabetic group,all above indexes of NAC treatment groups had been improved by gavage 12 weeks,high dose group had been improved obviously(P<0.01). Conclusions NAC has a protective effect on myocardial in diabetic rats,the mechanism may be related to the inhibition of oxidative stress,reducing the expression of TGF-β1,SMAD3 and increasing the expression of SMAD7.