吡格列酮对非酒精性脂肪性肝病大鼠血小板源生长因子-B和基质金属蛋白酶抑制因子-2表达的影响  

Effect of Pioglitazone on expression of PDGB-B and TIMP-2 in rats with non-alcoholic fatty liver disease

作　　者：杨志宏[1] 孔令亭[1] 于传亭[1] 

机构地区：[1]烟台市烟台山医院消化内科,山东烟台264000

出　　处：《中西医结合肝病杂志》2012年第3期161-164,I0003,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：烟台市科技局2010年立项课题(No.2010149-07)

摘　　要：目的:观察吡格列酮对非酒精性脂肪性肝病(NAFLD)大鼠肝组织血小板源生长因子B(PDGF-B)和基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响,并研究吡格列酮防治NAFLD发病和进展的疗效及作用机制。方法:选用雄性SD大鼠60只,随机分为正常对照组、模型对照组和吡格列酮组,每组20只。正常对照组大鼠给予普通饲料,其余组均给予高脂饲料;吡格列酮组大鼠在高脂饮食8周后吡格列酮10ml.kg-1.d-1灌胃。于第20周结束时将3组动物处死,取材备检。结果:①肝组织病理变化:模型对照组动物肝细胞均出现中、重度大泡性脂肪变、有明显的炎细胞浸润聚集,吡格列酮组肝细胞也出现较明显的脂肪变和炎症表现,但较模型对照组病变轻。②TIMP-2染色指数3组分别为1.22±0.31,4.52±0.61,1.89±0.45,PDGF-B表达面积3组分别为(0.82±0.13)、(3.79±0.32)、(0.91±0.27)μm2,模型对照组明显高于其他两组(P<0.05),吡格列酮干预后TIMP-2染色指数和PDGF-B表达面积明显降低(P<0.05)。结论:在高脂饮食诱导的NAFLD模型中PDGF-B和TIMP-2表达增强,吡格列酮可以明显改善模型动物肝脏脂肪变性、炎症活动、纤维化变性程度,同时能降低PDGF-B和TIMP-2表达水平,有抗炎、抗纤维化作用。Objective： To observe the effect of Pioglitazone on the expressions of platelet derived growth factor B （ PDGF- B） and tissue inhibitor of metalloproteinase-2 （TIMP-2） in the liver of rats with non-alcoholic fatty liver disease （NAFLD） , and explore the mechanism of Pioglitazone treating non-alcoholic fatty liver disease. Methods： sixty SD rats were randomly di- vided into the normal group, the model group and the Pioglitazone group. In normal group rats were fed with Normal diet as con- trois, NASH model was established by feeding rats with cholesterol-rich diet in model group, and in Pioglitazone group Pioglita- zone （10 ml·kg^-1·d^-1） were given by intragastric administration from the beginning of the eighth week. All the rats were sacrificed at the 20th week. The expression levels of PDGF-B and TIMP-2 were assayed by immunohistological chemistry. Re- sults： ①Hepatic tissue pathological change： there were obvious steatosis in model group and the Pioglitazone group, and steato- sis in model group was significantly more serious. Inflammatory reaction was common in the livers of model group, but were sel- dom seen in normol group. Although some inflammatory cell and cellular necrosis were seen in Pioglitazone group, the severity were more lighter than in model group. ②Expression character of TIMP-2 in the normal group, model group and Pioglitazone group, dye index were 1.22 ±0. 31, 4. 52 ±0. 61, 1.89 ±0. 45, the expression of PDGF-B were （0. 82±0. 13）, （3.79± 0. 32）, （0. 91±0. 27） μm^2, there was statistical significance in the normal group and model group （P 〈0. 05） . The expres- sion of TIMP-2 and PDGF-B remarkably decreased in Pioglitazone group than those of the model group （P 〈 0. 05） . Conclu- sion： PDGF-B and TIMP-2 are increased in steatosis model animals. Pioglitazone not only can decrease levels of serum lipid, but also decrease the expression of liver TIMP-2 and PDGF-B. Pioglitazone not only can improve steatosis, but also delay or/andblock

关 键 词：非酒精性脂肪性肝病 吡格列酮/药理作用 血小板源生长因子-B 基质金属蛋白酶抑制因子-2 大鼠 

分 类 号：R575.5[医药卫生—消化系统]