氯喹对全肝缺血再灌注大鼠肠上皮细胞凋亡及肠道细菌/内毒素移位的影响

目的：观察磷脂酶A2抑制刺氯喹（CQ）对全肝缺血再灌注大鼠肠上皮细胞凋亡及肠道细菌／内毒素移位的影响。方法：阻断肝门及肝上、肝下下腔静脉20min复制大鼠全肝缺血再灌注模型，将90只大鼠随机均分成假手术组（A组）、全肝缺血再灌注组（B组）和氯喹治疗组（C组），每组再根据观察时间段不同随机均分成3个亚组，A，B两组从股静脉注射1mL/kg生理盐水，C组注射CQ10mg／kg（溶于1mL／kg生理盐水）。观察各组全肝血流阻断20min（T0），再灌注4h（T1）门静脉血D-乳酸、肿瘤坏死因子（TNF-α）、内毒素（ET）浓度，门静脉血、肠系膜淋巴结、脾脏细菌生长情况，末端回肠黏膜组织丙二醛浓度，肠黏膜上皮细胞凋亡指数改变及大鼠再灌注后48h生存率。结果：与A组比较。B、C两组T0，T1门静脉血D-乳酸、TNF-α、内毒素浓度、肠黏膜组织丙二醛浓度升高（P〈0．05或P〈0．01），其中C组低于B组（P〈0．05）；B，C两组T1时门静脉血、肠系膜淋巴结、脾脏均培养出细菌，其中C组阳性率低于B组，A组未培养出细菌；B，C两组肠黏膜上皮细胞凋亡指数高于A组（P〈0．01或P〈0．05），其中B组凋亡指数高于C组（P〈0．05）；C组大鼠48h存活率高于B组（P〈0．05）。结论：氯喹具有抑制全肝缺血再灌注大鼠肠上皮细胞凋亡及肠道细菌／内毒素移位，提高大鼠生存率作用。

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OBJECTIVE: To observe the effect of chloroquine on the apoptosis of intestinal mucosa epithelial cell and enterogenous bacteria-endotoxin translocation after total hepatic ischemia-reperfusion in rats. METHODS: The rat total hepatic ischemia-reperfusion model was built by blocking the hepatic portal, suprahepatic and infrahepatic vena cava for 20 minutes. Ninety Sprague-Dawley rats were assigned randomly into the sham operation group (Group A, n = 30), total hepatic ischemia-reperfusion treatment group (Group B, n = 30), and chloroquine administrated group (Group C, n = 30). Each group was subdivided randomly into 3 subgroups (n = 10) according to different experiment time phases as follows: after 20 minutes of total hepatic vascular exclusion (T0), 4 hours after reperfusion (T1), and the 48 hours of survival. Group A and Group B were intravenously injected with normal saline 1 mL/kg while Group C received chloroquine 10 mg/kg which dissolved in 1 mL/kg normal saline intravenously. The levels of portal blood D-lactate, TNF-alpha, endotoxin, and the intestinal mucosa MDA concentration were measured at T0 and T1; the portal blood, mesenteric lymph node, and spleen tissues were cultured for bacteria; and the apoptotic index of intestinal mucosa epithelial cells at T0 and T1 and the survival rate after 48 hour reperfusion were obtained. RESULTS: Compared with Group A, the levels of portal blood D-lactate, TNF-alpha, endotoxin and the intestinal mucosa MDA in Group B and Group C were significantly higher (P < 0.05 or P < 0.01). These indexes of Group C were lower than those of Group B (P < 0.05). The portal vein blood, mesenteric lymph node and spleen tissues existed the bacterium translocation both in Group B and Group C, and the positive rate in Group C was lower than that in Group B (P < 0.05). Apoptotic index of the intestinal mucosa epithelial cell increased significantly in Group B (P < 0.01) and Group C (P < 0.05), but the apoptotic index in Group C was lower than that in Group B (P < 0.05); the 48 hour survival rate of the rats in Group C was higher than that in group B (P < 0.05). CONCLUSION: Chloroquine may decrease the intestinal mucosa epithelial cell apoptosis and the enterogenous bacteria-endotoxin translocation after total hepatic ischemia-reperfusion and increase the survival rate of the rats.