库普弗细胞在大鼠酒精性肝病发病机理中的作用

The role of kupffer cells in the pathogeny of alcoholic liver disease of rats

目的:研究库普弗细胞(KC)在酒精性肝病发病机理中的作用。方法:50只雄性wistar大鼠随机分为模型组(40只)和正常对照组(10只),模型组给予乙醇灌胃以建立大鼠酒精性肝病模型,分别于4周、8周、12周和16周处死大鼠,留取血清及肝组织,检测血清IL-1β、IL-6和TNF-α,检测肝匀浆ORF、ASOA、SOD及MDA含量,应用HE染色和苏丹Ⅳ染色观察肝组织病理形态,应用DPAS染色和流式细胞仪观察肝组织KC形态及数量变化。结果:随着造模时间的延长,肝细胞脂肪变性加重,乙醇灌胃16周大鼠肝脏呈现弥漫性小泡性肝细胞脂肪变、灶性坏死,流式细胞仪和DPAS染色显示肝组织KC数量明显增多,血清IL-1β、IL-6和TNF-α水平升高,KC荧光标记率与肝匀浆ORF、MDA呈正相关(相关系数分别为0.76和0.74,均P<0.01),与ASOA、SOD呈负相关(相关系数分别为-0.72和-0.66,均P<0.01)。结论:KC和致炎类细胞因子增多在酒精性肝病发病过程中发挥着重要作用。

Objective： To explore the role of kupffer cells（KC） in the pathogeny of alcoholic liver disease ALD） by rat model. Methods： Fifty male wistar rats were randomized into model group （n = 40） and normal group （n = 10）. The rat model of ALD were induced by intragastric administration of alcohol. At 4,8,12 and 16 weeks, liver and serum samples were collected respectively, The concentration of IL-1β,IL-6 and TNF-α in serum and the content of ORF, SOD, ASOA and MDA in the liver homogenate were measured respectively, Hepatic tissue were stained by hematoxylin eosin and Sudan Ⅳ. The number and shape of KC in the liver were detected by flow cytometry （FCM） and DPAS stanining respectively, Results,, At 16 weeks, histopathological examination showed hepatocellular microvesicular steatosis, lobular inflammatory cells infiltration and necrosis. The number of KC was largely increased compared with that in normal group, The level of IL-1β,IL-6 and TNF-α in serum increased significantly. The label rate of CD68 was positively correlated with the content of OFR and MDA （r= 0, 76 and 0, 74, both P〈0. 01）, and negatively correlated with the content of ASOA and SOD in the liver homogenate（r = -0, 72 and -0.66, both P〈0. 01）. Conclusions,, The increase in KC and the proinflammatory cytokines plays a pivotal role in the pathegenesis of ALD.