肝脏缺血再灌注时肝脏及小肠组织中MIP-1a、HIF-1a表达的相关性分析和意义探讨

The expressions of MIP - 1 a and HIF - 1 a in the rat liver during hepatic ischemia - reperfusion injury

目的探讨SD大鼠肝脏缺血45min后再灌注不同时限肝脏和小肠组织中MIP-1a和HIF-1a的不同表达、病理学变化及其意义。方法将75只SD大鼠随机分为正常组、假手术组、缺血再灌注组，建立肝缺血再灌注模型，采用免疫组织化学方法检测MIP-1a及HIF-1a在肝脏缺血45min再灌注0、3、12、24、72h时肝脏、小肠中的表达，HE组织染色及电镜观察大体及显微组织学变化。结果随着再灌注时限的延长，肝脏及小肠组织损伤加重，再灌注后24h最严重。与正常组及假手术组相比，缺血再灌注组中MIP-1a和HIF-1a在肝脏及小肠组织中的表达显著升高（P〈0．05）。两者在肝脏中的表达12h达顶峰，随后MIP—1a再灌注72h时基本恢复至再灌注初期水平，而HIF-1a降至正常水平。MIP—1a和HIF-1a在小肠组织中的表达24h达到峰值，再灌注72h后降至再灌注初期水平。MIP-1a与HIF-1a表达有相关性（P〈0．05）。结论肝脏缺血再灌注可以造成胃肠道组织的损伤；MIP-1a及HIF-1a均参与了肝脏缺血再灌注后的肝脏及胃肠道损伤，HIF-1a可能是MIP-1a表达的重要调节因子。

Objective To investigate the expressions of MIP -1a and HIF - 1 a, and the pathologic changes in the rat liver in hepatic ischemia - reperfusion injury. Methods SD rats （ n = 75 ） were randomly divided into three groups ： normal group （ CO ） , sham operative group （ SM ） , ischemia and reperfusion group（IR）. The rat model of hepatic ischemia and reperfusion was established. The expressions of MIP -1a and HIF - 1a were immunohistochemically detected at 0,3,12,24,72 h after ischemia. HE staining and electron microscopy were used to observe the pathological changes. Results The injury of hepatic and intestinal tissues aggravated with the reperfusion time extending, and was worst 24 h after the reperfusion. The expressions of MIP - 1a and HIF - 1a in the liver and small bowel in the IR group were obviously increased as compared with those in the CO and SM groups（ P 〈 0.05 ）. Both of them reach the peak at 12 h. Then, the expression of MIP- 1a declined to the level at early stage of reperfusion, while HIF - 1a expression returned to the normal level. The expressions of MIP -1a and HIF - 1a in the intestinal tissue reached the peak at 24 h. Then they declined to the level at the early stage of reperfusion. Conclusion Hepatic ischemia and reperfusion causes the damage of gastrointestinal tissues, which involves MIP - 1a and HIF - 1 a.