N-乙酰半胱氨酸在肠缺血再灌注肝损伤中保护作用的实验研究

PROTECTIVE EFFECT OF N-ACETYLCYSTEINE ON HEPATIC DAMAGE INDUCED BY INTESTINAL ISCHEMIA REPERFUSION IN RATS

目的 探讨 N-乙酰半胱氨酸 (n- acetylcysteine,NAC)在肠缺血再灌注时对 P-选择素 (P- selectin) m RNA和蛋白表达的影响及肝损伤的保护作用。方法 采用肠系膜上动脉夹闭的方法制作大鼠肠缺血再灌注模型 ,应用逆转录 -聚合酶链反应及免疫组织化学的方法观察肠、肝 P-选择素表达的变化 ,同时检测血、组织中髓过氧化物酶活性及肝功能指标丙氨酸转移酶的活性变化。结果 缺血再灌注 6 0分钟肝组织 Ps- m RNA表达最高 ,免疫组织化学显示其蛋白表达在肠缺血再灌注 6 0 min时增多。再灌注时给予 NAC治疗后肠、肝组织 Ps- m RNA及蛋白为低或不表达。血清丙氨酸转氨酶 (AL T)活性再灌注 30 min升高之后下降 ,再灌注 2 4 0 m in后达最高峰 2 71 .0 0± 2 9.89u/ l(P<0 .0 1 ) ,再灌注时 NAC治疗后明显下降。血清 MPO活性 I4 0 m in/ R30 m in达最高峰 1 4 8.83± 2 2 .80 u/ l(P<0 .0 1 ) ,再灌注时 NAC治疗后也明显下降。结论 NAC可抑制 p-选择素的表达 ,降低中性粒细胞 (PMN)与局部血管内皮细胞粘附、相互作用和激活 。

Objective To investigate protective effects of n acetylcysteine and expression onP selectin mRNA and pro tein on hepatic tissue during intestinal ischemia reperfusion.Methods The mRNA transcription and protein translation levels of P selectinwere assayed with nRT PCR and immunohistochemistry in an ischemia reperfusion rat model.Blood,gut,hepatic myeloperoxidase(MPO)activity and plasma alanine aminptransferase(ALT)were determined as well.Results The highest P selectin mRNA expression was found on the group of 1h post ischemia reperfusion and its protein expressionwere lower or not.ALT activity markedly increased as early as0.5h after reperfusion following decreased,and reached a peak at the 4h after reperfusion(271.00±29.89 u/l, P<0.01 ),then decreased obviously after treatment with n acetylcysteine at reperfu sion.MPO activity reached a peak at the 0.5h after reperfusion(148.83±22.80 u/l, P<0.01 )and decreased obviously after treatment with n acetylcysteine at reperfusion as well.Conlusion NAC could inbhibit both P selectin expression and de creased the activation of PMN in intestinal and hepatic tissue,and avoid hepatic damage induced by intestinal ischemia reperfu sion.