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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 investigate the effects of melatonin (MT) on the regulation of oxidative anti-oxidant system and the expression of the second mitochondrial caspase-6 (Smac) in streptozotocin-induced diabetic rats. Methods STZ-induced diabetic rats were randomly divided into diabetic group (DM group, 10 rats) and MT intervention group (MT group, 10 rats). The rats in normal group (NC group, n = 9) served as controls. After 8 weeks of intervention, creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBil), blood urea nitrogen (BUN), serum creatinine (SCr) and urinary protein excretion rate (UAER). Morphological changes of heart, liver and kidney were observed. Malondialdehyde (MDA) and the activity of superoxide dismutase (SOD). The expression of Smac protein in heart, liver and kidney was analyzed by immunohistochemistry. Results MT significantly improved the levels of heart, liver and kidney injury-related indicators and histopathology in diabetic rats, significantly decreased the content of MDA in serum and tissues, increased the activity of SOD and down-regulated the expression of Smac. Conclusion MT may play a protective role on the function of heart, liver and kidney of diabetic rats by regulating the balance of oxidative anti-oxidant system and down-regulating the expression of Smac.