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目的探讨肝细胞生长因子(Hepatocyte growth factor,HGF)对内质网应激参与的急性肝损伤的保护作用。方法 BALB/c小鼠随机分为正常组、模型组、治疗组,采用50%浓度的CCl4植物油溶液2ml/kg腹腔注射小鼠建立CCl4急性肝损伤模。治疗组以尾静脉注射法为每只小鼠注入20μg将HGF质粒(pCMV-HGF),经8h处理后再次给予50%浓度的CCl4植物油溶液2ml/kg腹腔注射,正常对照组和模型组注射等量的含p CDNA3的质粒(20μg/只)生理盐水。分别于造模前和造模后各48h取小鼠血样(眼眶)及同一小鼠肝组织。以ELISA法检测小鼠血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)的水平,蛋白免疫印迹法定量检测肝细胞GRP78的蛋白表达情况。结果与模型组比较,HGF显著降低CCl4肝损伤小鼠ALT、AST水平,同时HGF能抑制肝组织中GRP78蛋白表达。结论肝细胞生长因子可能是通过抑制内质网应激介导的肝细胞凋亡,进而发挥肝保护作用。
Objective To investigate the protective effect of hepatocyte growth factor (HGF) on acute liver injury induced by endoplasmic reticulum stress. Methods BALB / c mice were randomly divided into normal group, model group and treatment group. CCl4 acute liver injury model was established by intraperitoneal injection of 2% / kg CCl4 vegetable oil solution at 50% concentration. In the treatment group, 20 μg of HGF plasmid (pCMV-HGF) was injected into each mouse by tail vein injection, and then 2 ml / kg of CCl4 vegetable oil solution was intraperitoneally injected 50% of the concentration of CCl4 after 8 hours of treatment. The normal control group and the model group were injected Of pCDNA3-containing plasmid (20 μg / mouse) normal saline. Blood samples (orbital) and the same mouse liver tissue were taken before and 48 h after modeling. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by ELISA. Western blotting was used to detect the protein expression of GRP78 in liver cells. Results Compared with the model group, HGF significantly reduced the levels of ALT and AST in CCl4-induced liver injury and HGF inhibited the expression of GRP78 protein in liver tissue. Conclusion Hepatocyte growth factor may play a protective role by inhibiting endoplasmic reticulum stress-induced hepatocyte apoptosis.