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目的探讨凝血酶抑制剂比伐卢定逆转大鼠非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)的效果。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、细胞间黏附分子-1(ICAM-1)、巨噬细胞炎性蛋白-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(TGF-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(P=0.000);比伐卢定可以明显降低CD68及F4/80mRNA、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(P<0.05);比伐卢定可以明显降低α-SMA蛋白表达和COL1A1 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。
Objective To investigate the effect of thrombin inhibitor bivalirudin on reversing nonalcoholic fatty liver disease (NAFLD) in rats. Methods Rat model of NAFLD was induced by feeding high-fat diet, liver and serum lipids were detected by ELISA, MCP-1, CD68 and ICAM- 1, MIP-2, COL1A1, TIMP-1 and TGF-β1 Levels, liver tissue section oil red O staining, HE staining, under a microscope. Results Bivalirudin significantly prolonged the prothrombin time (P = 0.000). Bivalirudin significantly reduced the levels of CD68, F4 / 80 mRNA, MCP-1 mRNA and MCP-1 in liver and serum, (P <0.05). Serum triglycerides and total cholesterol in the bivalirudin group were significantly lower than those in the placebo group (P <0.05). Bivalirudin was significantly lower α-SMA protein expression and COL1A1 mRNA, TIMP-1 mRNA expression compared with the placebo group, the difference was statistically significant (P <0.05). Conclusion The thrombin inhibitor bivalirudin can reduce macrophages and neutrophils accumulation in the liver, correct the inflammatory state of liver cells, lower serum triglyceride and total cholesterol, and reduce the risk of liver fibrosis.