褪黑素对糖尿病大鼠氧化抗氧化系统及Smac表达的影响

Effect of melatonin on oxidative and anti-oxidative system and expression of Smac in diabetic rats

目的探讨褪黑素(MT)对链脲佐菌素(STZ)诱导的糖尿病大鼠氧化抗氧化系统的调控及第二线粒体源半胱天冬氨酸蛋白酶激活物(Smac)表达的影响。方法 STZ诱导糖尿病大鼠模型后随机分为糖尿病组(DM组,10只)和MT干预组(MT组,10只),并以正常组(NC组,9只)作对照。干预8周后,检测大鼠心肝肾损伤相关指标肌酸激酶(CK)、乳酸脱氢酶(LDH)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、总胆红素(TBil)、血尿素氮(BUN)、血肌酐(SCr)、尿蛋白排泄率(UAER)水平;观察心、肝、肾组织形态学变化;测定血清及心、肝、肾组织中丙二醛(MDA)的含量及超氧化物歧化酶(SOD)活性;免疫组化法分析心、肝、肾中Smac蛋白的表达。结果 MT显著改善糖尿病大鼠心肝肾损伤相关指标的水平及大鼠组织病理形态,明显降低血清及各组织中MDA的含量,增强SOD的活性,下调Smac的表达。结论 MT可能通过调节氧化抗氧化系统平衡,下调Smac的表达,发挥对糖尿病大鼠心脏、肝脏、肾脏功能的保护作用。

Objective To observe the effects of melatonin（MT）on oxidative and anti-oxidative system and expression of Smac on the heart,liver,kidney in streptozotocin（STZ）-induced diabetic rats.Methods Adult SD rats were randomized into normal group（NC,9 rats）and diabetic group DM（10 rats without treatment）and group MT（10 rats）treated with MT for 8 weeks.Eight weeks later,creatine kinase（CK）,lactate dehydrogenase（LDH）,aspartate aminotransferase（AST）,alanine aminotransferase（ALT）,bilirubin（Bil）,urinary albumin excrection rate（UAER）,serum creatinine（SCr）and serum urea nitrogen（BUN）were detected.Morphological changes of the heart,liver and kidney were observed.The levels of malondialdehyde（MDA）and the activity of superoxide dismutase（SOD）were detected in serum,heart,liver and kidney.Meanwhile,the expression of Smac was detected by immunohistochemistry.Results Treatment with MT significantly decreased the levels of LDH,CK,AST,ALT,Bil,BUN,SCr and UAER,attenuated the abnormal histopathological phenomenon obviously in the heart,liver and kidney of diabetic rats in group MT.Meanwhile,the level of MDA was significantly reduced and the activity of SOD elevated by treated with MT in the heart,liver and kidney.The expression of Smac protein was down-regulated in group MT.Conclusion MT protects the function and structural changes of the heart,liver and kidney in diabetic rats through improving oxidative and anti-oxidative system and down-regulating the expression of Smac.