生长抑素通过抑制内质网应激反应减轻肝纤维化小鼠肝损伤研究

目的 观察生长抑素(SST)对肝纤维化(LF)小鼠肝组织内质网应激(ERS)反应的影响。方法 将40只野生型小鼠随机分为对照组、模型组、小剂量SST干预组和大剂量SST干预组,给予小鼠腹腔内注射25% CCl₄ 橄榄油混合制剂制备肝纤维化模型,分别给予大、小剂量的SST进行干预。取肝组织行天狼猩红和免疫组化染色,对肝组织行Ishak评分,采用Western blot法检测肝组织Bcl-2、Bax、Casp-9、BiP和CHOP蛋白表达变化。结果 模型组肝组织炎症活动度评分为(12.2±2.7),显著高于对照组(1.8±0.8),P＜0.01],肝纤维化程度评分为(5.4±0.5),显著高于对照组(0.1±0.3),P＜0.01];血清AST 和ALT水平分别为(194.7±35.2)U/L和(121.8±26.6)U/L],均显著高于对照组分别为(53.8±21.7)U/L和(35.3±12.9)U/L,P＜0.01];大、小剂量SST干预组小鼠肝脏炎症活动度评分分别为(7.7±2.1)和(6.9±1.97),肝纤维化程度评分分别为(4.3±1.0)和(3.9±0.9),较模型组显著改善(P＜0.05);模型组肝组织Bax、Casp-9、BiP和CHOP蛋白相对表达量显著强于对照组(P＜0.01),而SST干预组Bax、Casp-9、BiP和CHOP蛋白相对表达量均显著弱于模型组(F=26.36,F=14.81,F=25.11和F=30.31,P＜0.05)。结论 SST能够改善CCl₄诱导的肝纤维化小鼠肝组织炎症活动和纤维化程度,其机制可能与其抑制了肝组织ERS反应有关。

Somatostatin alleviates liver injury in mice with liver fibrosis by inhibiting endoplasmic reticulum stress

Objective The aim of this study was to observe the effects of somatostatin(SST)on the inflammatory response and apoptosis in mice with CCl4-induced liver fibrosis(LF),and to investigate whether SST can reduce liver injury and alleviate the process of LF by inhibiting the ERS.Methods Forty WT mice were randomly divided into control,model,low-dose SST-intervened and large-dose SST-intervened group,with 10 in each.Except the mice in control,the mice in other groups were injected with 25%CCl4 and oil mixture intraperitoneally to establish the model of liver injury and the mice in SST-intervened groups were given large or low doses of SST subcutaneously,respectively.Serum ALT and AST were detected,the liver tissues were obtained for pathological examination,and the protein expression of Bcl-2,Bax,Casp-9,BiP and CHOP in liver tissues were detected by Western blot.Results The histological activity index(HAI)score in model group was(12.2±2.7),significantly higher than(1.8±0.8),P<0.01]in the control,and the hepatic fibrosis score was(5.4±0.5),significantly higher than(0.1±0.3),P<0.01]in control;serum AST and ALT in the model were(194.7±35.2)U/L and(121.8±26.6)U/L],both significantly higher than(53.8±21.7)U/L and(35.3±12.9)U/L,respectively,P<0.01]in the control;the HAI scores in low-dose and large-dose SST-intervened groups were(7.7±2.1)and(6.9±2.0),and the hepatic fibrosis scores were(4.3±1.0)and(3.9±0.9),significantly decreased compared to those in the model(P<0.05);the expression of Bax,Casp-9,BiP and CHOP in hepatic tissues in the model intensified greatly compared to in the control(P<0.01),while the hepatic expression of Bax,Casp-9,BiP and CHOP in SST-intervened groups weaken obviously compared to in the model(F=26.36,F=14.81,F=25.11 and F=30.31,P<0.05).Conclusion SST could alleviate liver inflammation and LF,the mechanism by which might be related to the inhibition of ERS.