坎地沙坦对糖尿病心肌纤维化及氧化应激、NF-κB的抑制作用

Inhibition Effects of Candesartan on Myocardial Fibrosis,Oxidative Stress,and NF-κB Expression in Diabetic Rats

目的:研究坎地沙坦(Candesartan)对糖尿病大鼠心肌纤维化及氧化应激、NF-κB表达的影响。方法:30只雄性SD大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)和坎地沙坦干预组(Cand组)。腹腔注射链脲佐菌素诱导糖尿病大鼠模型,Cand组于造模成功后给予坎地沙坦8mg/(kg·d)灌胃。12周末取血及心脏标本,测定血糖、心脏质量指数(HMI)及左心室质量指数(LVMI);Masson染色观察心肌形态及测算心肌间质胶原容积分数(CVF)(%),测定血清和左心室心肌组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)的活性及还原型谷光甘肽(GSH)含量变化;Western法及免疫组织化学方法检测左心室心肌NF-κB p65及TNF-α蛋白表达水平。结果:与NC组比较,DM组HMI、LVMI显著增加(P<0.01),血清及心肌MDA含量显著增高,GSH含量及SOD活性均显著降低(P<0.05);心肌NF-κB p65及TNF-α表达明显升高;心肌细胞排列紊乱,胶原纤维增多,CVF明显升高(P<0.01)。与DM组比较,Cand组HMI、LVMI降低(P<0.05),血清及心肌MDA含量降低,SOD及GSH明显增高(P<0.05);Cand组心肌NF-κB p65及TNF-α表达明显减少(P<0.01);心肌间质纤维减少,CVF下降(P<0.01)。结论:坎地沙坦可通过抑制氧化应激及NF-κB活化、下调TNF-α表达,抑制糖尿病心肌纤维化。

Objective：To investigate the effect of candesartan on myocardial fibrosis and the level of oxidative stress and the expression of NF-κB p65 in the myocardium of diabetic rats.Methods：Thirty male Sprague Dawley（SD）rats were randomly divided into control group（NC）,diabetes group（DM）,and candesartan treated group（Cand）.Diabetic animal models were induced by intraperitoneal injection of streptozotocin.Rats in candesartan group were administrated with 8mg/kg by gavage daily for 12 weeks.At the end of 12 th week,the blood glucose,body weight,heart mass indexes（HMI）and left ventricle mass indexes（LVMI）were measured.Myocardial morphology was observed by Masson staining and myocardial interstitium collagen volume frac-tion（CVF）（%）was also measured.The contents of malondialdehyde（MDA）and reduced glutathione hormone（GSH）,the activity of superoxide dismutase（SOD）in plasma and left cardiac muscle were assayed.Western blot and immunohistochemistry were used to detect the expressions of NF-κB p65 and TNF-αin the left myocardium.Results：Compared with that respectively in control group,HMI and LVMI were obviously increased（P〈0.01）,the content of MDA were significantly higher while the content of GSH and activity of SOD were significantly lower（P〈0.05）,the expression of NF-κB p65 and TNF-αproteins in the left myocardium were higher（P〈0.01）,myocardial cells arranged disorderly,collagen fibers increased and myocardial interstitium CVF obviously elevated in diabetes group（P〈0.01）.Compared with that respectively in diabetes group,in candesartan treated group,HMI and LVMI were decreased（P〈0.05）,the content of MDA was lower and the content of GSH and activity of SOD were significantly elevated（P〈0.05）,the expression of NF-κB p65 and TNF-αproteins in the left myocardium decreased（P〈0.01）,collagen fibers decreased and myocardial interstitium CVF declined（P〈0.01）.Conclusion：Candesartan can inhibit diabetic myocardial fibrosis,partly through attenuating oxidative stress and inhibiting activation of NF-κB p65,and downregulating the expression of TNF-αprotein.