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目的探讨家兔肝脏缺血再灌注损伤的机制及N-乙酰半胱氨酸(NAC)对兔肝组织的保护作用。方法 40只成年兔(3~4周龄),体质量3.5~4.5 kg,随机分为肝缺血再灌注组(IR组)和肝缺血再灌注+NAC组(IR+NAC组),于门静脉阻断前(T0)、门静脉开放即刻(T1)、开放后2 h(T2)、5 h(T3)和7 h(T4)分别采用全自动生化分析仪测定各组血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平;黄嘌呤氧化酶法测定血清丙二醛(MDA)和超氧化物岐化酶(SOD)活性;TUNEL法和琼脂糖凝胶电泳法检测肝细胞凋亡并计算凋亡指数。结果与T0比较,2组T1、T2、T3、T4各时间点ALT、AST及MDA显著升高、SOD显著降低;与IR组比较,IR+NAC组T1、T2、T3、T4各时间点ALT、AST及MDA明显下降而SOD明显升高,肝脏病理损伤改善;与IR组比较,IR+NAC组在再灌注后5 h、7 h,凋亡细胞减少及细胞凋亡率明显降低。结论 NAC对家兔肝脏缺血再灌注损伤有明显的保护作用,其可能机制与NAC清除氧自由基从而抑制肝细胞凋亡有关。
Objective To investigate the mechanism of hepatic ischemia-reperfusion injury in rabbits and the protective effect of N-acetylcysteine (NAC) on liver of rabbits. Methods Forty adult rabbits (3 to 4 weeks old) and 3.5 to 4.5 kg body weight were randomly divided into two groups: IR group and IR + NAC group Serum levels of alanine aminotransferase were determined by automatic biochemical analyzer before portal vein occlusion (T0), immediately after portal vein opening (T1), 2 h (T2), 5 h (T3) and 7 h (ALT) and serum aspartate aminotransferase (AST) levels were measured. The serum malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by xanthine oxidase method. TUNEL and agarose gel electrophoresis Method to detect hepatocyte apoptosis and calculate apoptosis index. Results Compared with T0, the levels of ALT, AST and MDA were significantly increased and the SOD was significantly decreased in the two groups at T1, T2, T3 and T4. Compared with IR group, the levels of ALT , AST and MDA decreased obviously, SOD increased obviously and liver pathological injury improved. Compared with IR group, the apoptotic rate and apoptosis rate of IR + NAC group decreased obviously at 5 h and 7 h after reperfusion. Conclusion NAC has a protective effect on hepatic ischemia-reperfusion injury in rabbits, and its possible mechanism is related to NAC scavenging oxygen free radicals to inhibit hepatocyte apoptosis.