N-乙酰半胱氨酸对糖尿病大鼠心肌缺血再灌注后肝肾功能的影响

Effect of N-acetylcysteine on liver and kidney function after myocardial ischemia reperfusion in diabetic rats

目的探讨抗氧化剂N-乙酰半胱氨酸(N-acetylcysteine,NAC)对糖尿病大鼠心肌缺血再灌注(ischemia reperfusion,IR)损伤后肝、肾功能的影响。方法36只雄性SD大鼠随机分为对照假手术组、对照IR组、糖尿病假手术组、糖尿病IR组、糖尿病NAC治疗后假手术组和糖尿病NAC治疗后IR组,每组各6只。糖尿病假手术组、糖尿病IR组、糖尿病NAC治疗后假手术组和糖尿病NAC治疗后IR组大鼠经腹腔注射链脲佐菌素60 mg/kg制备1型糖尿病模型。糖尿病模型制备成功1周后,糖尿病NAC治疗后假手术组和糖尿病NAC治疗后IR组大鼠灌胃给予NAC 1.5 g/(kg·d),其余各组大鼠给予等体积生理盐水,持续4周,对照IR组、糖尿病IR组和糖尿病NAC治疗后IR组通过结扎左冠状动脉前降支30 min,再灌注120 min制备IR模型。采用生物化学法检测大鼠血清谷丙转氨酶(glutamate pyruvic transaminase,GPT)、谷草转氨酶(glutamic oxaloacetic transaminase,GOT)、乳酸脱氢酶(lactate dehydrogenase,LDH)、肌酸激酶(creatine kinase,CK)、肌酐(serum creatinine,SCr)水平,采用WST-1法检测大鼠血清超氧化物歧化酶(superoxide dismutase,SOD)活性,采用TBA法检测大鼠血清过氧化物丙二醛(peroxide malondialdehyde,MDA)水平。结果糖尿病4组大鼠血清GPT、GOT、LDH、SCr及MDA水平均高于对照IR组和对照假手术组(P<0.05),血清SOD活性低于对照假手术组(P<0.05)。糖尿病NAC治疗后IR组大鼠血清GPT、GOT、LDH、SCr水平低于糖尿病IR组(P<0.05),血清MDA水平[(19.38±0.56)μmol/L]低于糖尿病IR组[(27.75±1.30)μmol/L](P<0.05),SOD活性[(128.85±7.28)u/mL]高于糖尿病IR组[(105.72±10.13)u/mL](P<0.05)。糖尿病NAC治疗后假手术组大鼠血清GPT、GOT、LDH、SCr水平低于糖尿病假手术组(P<0.05),血清MDA水平[(13.38±0.62)μmol/L]低于糖尿病假手术组[(19.90±1.30)μmol/L](P<0.05),SOD活性[(177.33±6.20)u/mL]高于糖尿病假手术组[(153.24±8.89)u/mL](P<0.05)。糖尿病NAC治疗后IR组大鼠血清GPT、GOT、LDH、SCr和MDA水平高于糖尿病NAC治疗后假手术组(P<0.05),SOD活性低于糖尿病NAC治疗后假手术组(P<0.05)。糖尿病IR组大鼠血清GPT、GOT、LDH、SCr和MDA水平高于糖尿病假手术组(P<0.05),SOD活性低于糖尿病假手术组(P<0.05)。结论NAC可减轻糖尿病大鼠合并IR损伤模型的氧化应激反应,从而降低对肝、肾功能的损伤。

Objective To investigate the effect of antioxidant N-acetylcysteine(NAC)on liver and kidney function after myocardial ischemia reperfusion(IR)injury in diabetic rats.Methods Thirty-six male SD rats were randomly divided into control sham operation group,control IR group,diabetic sham operation group,diabetic IR group,diabetic NAC treated sham operation group,and diabetic NAC treated IR group,with 6 rats in each group.Type 1 diabetes models were established by intraperitoneal injection of streptozotocin 60 mg/kg in diabetic sham operation,diabetic IR,diabetic NAC treated sham operation and diabetic NAC treated IR groups.One week after modeling,diabetic NAC treated sham operation,and diabetic NAC treated IR groups were given NAC 1.5 g/(kg·d)by gavage for 4 weeks,and the other groups were given an equivalent volume of normal saline.IR models were established by ligating the left anterior descending for 30 min and reperfusion for 120 min in control IR,diabetic IR and diabetic NAC treated IR groups.The levels of glutamate pyruvic transaminase(GPT),glutamic oxaloacetic transaminase(GOT),lactate dehydrogenase(LDH),creatine kinase(CK)and serum creatinine(SCr)were detected by biochemical methods,the serum superoxide dismutase(SOD)activity was determined by WST-1 method,and the serum peroxide malondialdehyde(MDA)level was determined by TBA method.Results The serum levels of GPT,GOT,LDH and SCr were higher in diabetic groups than those in control groups(P<0.05),and the SOD activities were lower in diabetic groups than those in control sham operation group(P<0.05).The serum levels of GPT,GOT,LDH and SCr were lower in diabetic NAC treated IR group than those in diabetic IR group(P<0.05).The MDA level was lower and the SOD activity was higher in diabetic NAC treated IR group((19.38±0.56)μmol/L,(128.85±7.28)u/mL)than that in diabetic IR group((27.75±1.30)μmol/L,(105.72±10.13)u/mL)(P<0.05).The serum levels of GPT,GOT,LDH and SCr were lower in diabetic NAC treated sham operation group than those in diabetic sham operation group(P<0.05).The MDA level was lower and the SOD activity was higher in diabetic NAC treated sham operation group((13.38±0.62)μmol/L,(177.33±6.20)u/mL)than that in diabetic sham operation group((19.90±1.30)μmol/L,(153.24±8.89)u/mL)(P<0.05).The serum levels of GPT,GOT,LDH,SCr and MDA were higher in diabrtic NAC treated IR group than those in diabetic NAC treated sham operation group(P<0.05),and the SOD activity was lower than that in diabetic NAC treated sham operation group(P<0.05).The levels of GPT,GOT,LDH,SCr and MDA were higher in diabetic IR group than those in diabetic sham operation group(P<0.05),and the SOD activity was lower than that in diabetic sham operation group(P<0.05).Conclusion NAC may alleviate the liver and kidney function damage by reducing oxidative stress after IR injury in diabetic rat models.