吡格列酮对非酒精性脂肪肝病大鼠Kupffer细胞的影响

目的探讨吡格列酮对sD大鼠非酒精性脂肪肝病形成的预防作用及其机制。方法36只雄性SD大鼠按随机数字表法分为正常对照组、高脂饮食组及吡格列酮干预组，饲养8周；正常对照组喂饲普通饲料，剩余两组喂饲高脂饲料；吡格列酮干预组于实验第4—8周予吡格列酮灌胃，其余两组同期予蒸馏水灌胃；测定空腹血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、甘油三酯（TG）、总胆固醇（TC）、空腹血糖（FPG）、空腹胰岛素（FINS）水平；计算空腹胰岛素抵抗指数（FIRI）；HE染色分析肝组织切片病理学改变；观察Kupffer细胞形态变化及分泌肿瘤坏死因子-α（TNF-α）、一氧化氮（NO）的水平。结果高脂饮食组大鼠空腹FIRI、TG、TC均高于正常对照组，差异均有统计学意义（P＜0．05），肝组织呈以大泡性脂肪变性为主的混合性脂肪变性并出现炎症细胞浸润，肝脏Kupffer细胞发生形态改变，其产生的TNF-α、NO水平与肝组织病理学改变呈正相关（P＜0．05）；吡格列酮干预组大鼠空腹FIRI、TG、TC均低于高脂饮食组，差异均有统计学意义（P＜0．05），肝组织结构基本正常，肝脏Kupffer细胞形态及功能基本正常。结论吡格列酮可预防高脂饮食诱导的非酒精性脂肪肝病发生；其机制可能与改善胰岛素抵抗、降低血脂和调节Kupffer细胞功能有关。

The effects of pioglitazone on the Kupffer cells of nonalcoholic fatty liver disease in rats

Objective To explore the preventive effect and mechanism of pioglitazone on nonalcoholic fatty liver disease in rats. Methods Thirty six male Sprague-Dawley （SD） rats were randomly divided into normal control group, high-fat diet group, and pioglitazone intervention group, with 12 rats in each group. Normal control group fed with standard diet for eight weeks, and the rest two groups fed with high fat diet. Pioglitazone intervention group fed with pioglitazone in the four to eight weeks, the rest two groups in the same period fed with distilled water. Fasting serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, fasting glucose, and fasting blood insulin levels were determined. The fasting insulin resistance index was calculated. Routine histological features of hepatic section were observed by hematoxylin eosin （HE） staining. The shape change of Kupffer cells in the liver was detected. The levels of tumor necrosis factor （TNF）-et and nitric oxide （NO） secreted by Kupffer ceils were measured. Results The fasting insulin resistance index, triglycerides, and total cholesterol in rats of high-fat diet group were significantly higher than in normal control group（ P〈0.05 ）. Histopathological examination showed hepatocellular macrove sicular steatosis, lobular inflammatory cell infiltration, and inflammatory cell infiltration. Hepatic Kupffer cell morphology change, its produced TNF, NO and liver tissue pathology changes were positively correlated （ P 〈0. 05）. The fasting insulin resistance index, triglycerides, total cholesterol was significantly lower in rats of pioglitazone intervention group than the high-fat diet group （ P〈0. 05）. The liver tissue structure was obviously improved pioglitazone intervention group rats, morphology and function of liver Kupffer cells were normal. Conclusions Pioglitazone can prevent the nonalcoholic fatty liver disease induced by high fat diet. The mechanism may be related to improve insulin resistance, reduce