比伐卢定对逆转大鼠非酒精性脂肪肝的试验研究-第三军医大学学报.DOC

比伐卢定逆转大鼠非酒精性脂肪肝的实验研究 马 娜，傅 念 （421002，湖南 衡阳南华大学附属南华医院消化内科onalcoholic fatty liver disease ，NAFLD）的效果，为非酒精性脂肪肝的药物治疗提供依据。方法 通过喂养高脂饲料复制NAFLD大鼠模型，ELISA法检测肝脏及血清血脂指标，RT-PCR法检测肝脏单核细胞趋化蛋白（MCP-1）、CD68、intercellular adhesion molecule -1，ICAM-1）、巨噬细胞炎性蛋白-2（macrophage inflammatory protein-2，MIP-2）、Ⅰ型胶原蛋白（COL1A1）、基质金属蛋白酶抑制因子-1（TIMP-1）、转化生长因子-β1（β1）mRNA表达水平，肝组织切片油红O染色、HE常规染色，显微镜下观察。结果 比伐卢定可以明显延长大鼠的凝血酶原时间（t=12.397, P=0.000）；比伐卢定可以明显的降低CD68及F4/80 mRNA、MCP-1 mRNA水平和肝脏及血清MCP-1水平，与安慰剂组相比，差异具有统计学意义（P＜0.05）；比伐卢定组大鼠的血清甘油三酯和总胆固醇比安慰剂组明显下降，差异具有统计学意义（P＜0.05）；比伐卢定可以明显的降低α-SMA蛋白表达和COL 1A1 mRNA、TIMP-1 mRNA表达，与安慰剂组比较，差异具有统计学意义（P＜0.05）。结论 凝血酶抑制剂比伐卢定可降低巨噬细胞和中性粒细胞在肝脏的聚集，纠正肝脏细胞的炎症状态，降低血清甘油三酯和总胆固醇的水平，并降低肝脏纤维化的风险，为预防和逆转NAFLD带来新希望。 [关键词] 比伐卢定；非酒精性；脂肪肝 [中图法分类号] [文献标志码] A Experimental Study on the Effect of Bivalirudin in Reversing Nonalcoholic Fatty Liver in Rats Ma Na, Fu Nian（Digestive system department of affiliated hospital of South China University, hunan, hengyang, 421002） [Abstract] Objective To investigate the effect of the thrombin inhibitor bivalirudin in reversing Nonalcoholic fatty liver disease (NAFLD) in rats and to provide a drug therapy for non-alcoholic fatty liver disease. Methods NAFLD rats model were replication by feeding high fat diet, liver and serum lipid levels was detected by ELISA assay, liver monocyte chemoattractant protein (MCP-1), CD68, intercellular adhesion molecule -1 (ICAM-1), macrophage inflammatory protein-2 (MIP-2), I collagen (COL1A1), matrix metalloproteinase inhibitor -1 (TIMP-1), transforming growth factor-β1 (TGF-β1) mRNA expression levels were detected by RT-PCR assay, liver biopsy oil red O staining and HE conventional staining. Results Bivalirudin can significantly prolong the prothrombin time (t=12.397, P=0.000) and significantly reduce CD68 and F4/80 mRNA, MCP-1 mRNA levels, liver and serum MCP-1, compared with placebo, the difference was statistically significant (P0.05). Compared with the placebo gr