伊伐布雷定对糖尿病大鼠心肌的保护作用及机制探讨

Improvement effect of Ivabradine on the myocardial interstitial fibrosis and cytokines levels of diabetic rats

目的研究伊伐布雷定(ivabradine,Iva)对糖尿病(DM)大鼠心肌的保护作用及机制。方法建立链脲佐菌素(STZ)诱导Ⅰ型糖尿病大鼠模型,将54只实验大鼠随机分为对照(NC)组、DM组、Iva低、中、高剂量组、阳性对照药(卡维地洛)组。测血糖、体重、心脏重量和血清中乳酸脱氢酶(LDH)、肌酸激酶(CK),同时测定心肌组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,观察心肌结缔组织生长因子(CTGF)表达的变化。结果与NC组相比,DM组大鼠血清中LDH、CK活性显著升高(P<0.05),心肌组织SOD活性显著降低(P<0.05),经Iva治疗后LDH、CK活性显著降低,SOD活性显著升高(P<0.05);DM组心肌中MDA含量与NC组相比显著升高,Iva组MDA含量升高显著降低(P<0.05)。与NC组相比,DM组大鼠心肌中CTGF表达显著升高(P<0.05),应用Iva干预治疗后,CTGF表达的升高显著被抑制(P<0.05)。结论 Iva可显著升高糖尿病大鼠心肌组织SOD活性,抑制CTGF表达升高和脂质过氧化,从而对糖尿病大鼠心肌损伤产生保护作用。

Objective To investigate the effect of Ivabradine （ Iva） on the myocardial injury and the potential mechanisms of diabetic rats.Methods Diabetic rats were induced by intraperitoneal injection of streptozotocin .The alterations of weight,blood glucose,and heart weight were assessed respectively .The serum lactate dehydrogenase （LDH）,creatine kinase（CK） activities,and superoxide dis-mutase（SOD） activities as well as malondialdehyde （MDA） content in myocardium were also determined .Furthermore,the expressions of CTGF in myocardium were examined by western blot .Results In DM group,body weight of rats was significantly decreased ,while blood glucose was not significantly higher as compared with control group （P＆lt;0.05）.The activities of LDH and CK in serum were sig-nificantly higher than those of NC group ,which could be significantly suppressed by Iva treatment （P＆lt;0.05）.However,SOD in myo-cardium of DM group was significantly lower than that of control group （P＆lt;0.05）,which could be suppressed by Iva treatment （P＆lt;0.05）.Moreover,the MDA level and CTGF expression in myocardium of DM group were markedly upregulated as compared with DM group,while these alterations were significantly attenuated by Iva （P＆lt;0.05）.Conclusions Iva has a protective effect on myocardial injury in diabetic rats ,which might be associated with suppressing the alterations of SOD activities and the increase of CTGF expression in myocardium .