摘要
目的:研究加味四逆散对慢性温和不可预知性应激(CUMS)结合孤养法制作抑郁模型所致肝损伤的保护作用。方法:将48只SD雄性大鼠随机分为6组,正常组,抑郁模型组,氟西汀(1.58 mg·kg-1·d-1)组,和加味四逆散低、中、高剂量(3.67,7.34,14.68 g·kg-1·d-1)组,每组8只。造模给药结束后,采用生化试剂盒法检测各组大鼠血清中丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST)水平和肝脏组织中炎症因子肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)水平。采用蛋白免疫印迹法(Western blot)检测加味四逆散对肝细胞中半胱氨酸蛋白酶-3(Caspase-3),活化型半胱氨酸蛋白酶-3(cleaved Caspase-3)蛋白表达的干预作用。结果:生化试剂盒检测显示,与正常组比较,模型组大鼠血清中的ALT,AST水平明显升高(P<0.05),肝脏组织中炎症因子TNF-α,IL-1β和IL-6水平明显升高(P<0.05);与模型组比较,加味四逆散低、中剂量组可降低血清中ALT,AST和炎症因子TNF-α,IL-1β和IL-6水平(P<0.05,P<0.01)。Western blot检测显示,与正常组比较,模型大鼠肝细胞中的Caspase-3蛋白表达下降,cleaved Caspase-3蛋白表达上升(P<0.05);与模型组比较,加味四逆散低、中剂量组可以上调Caspase-3蛋白的表达,下调cleaved Caspase-3蛋白的表达(P<0.05,P<0.01)。结论:慢性应激反应所致抑郁模型可造成肝损伤,加味四逆散能够通过调节多种生理生化和炎症因子指标的水平,抑制肝脏细胞凋亡来达到保肝作用。
Objective:To study the protective effect of modified Sinisan on liver injury caused by chronic unpredictable mild stress(CUMS)combined with solitary nutrition method based on a depression model.Method:Forty-eight SD male rats were randomly divided into normal group,depression model group,fluoxetine group(1.58 mg·kg-1·d-1),and low,medium and high-dose modified Sinisan(3.67,7.34,14.68 g·kg-1·d-1)groups,with 8 rats in each group.After the administration of the model,the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and the levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in liver tissues were measured by a biochemical kit method.Western blot was used to detect the expressions of cysteine aspastic acid-specific protease-3(Caspase-3)and cleaved Caspase-3 in liver cells after intervention with modified Sinisan.Result:Compared with the normal group,the biochemical test showed that the levels of ALT and AST in the serum of the model group were significantly increased(P<0.05),and the levels of inflammatory factors TNF-α,IL-1βand IL-6 in liver tissue significantly increased(P<0.05).Compared with the model group,low,medium-dose modified Sinisan groups significantly reduced serum ALT,AST and inflammatory factors TNF-α,IL-1βand IL-6 levels(P<0.05).Western blot showed that compared with the normal group,the protein expression of Caspase-3 in model rat liver cells decreased,while the protein expression of cleaved Caspase-3 increased(P<0.05,P<0.01).Compared with the model group,low,medium-dose modified Sinisan groups could up-regulate Caspase-3 protein expression,and down-regulated the expression of cleaved Caspase-3 protein(P<0.05,P<0.01).Conclusion:Chronic stress-induced depression model can cause liver damage.Modified Sinisan can have the hepatoprotective effect by regulating the levels of various physiological,biochemical and inflammatory factor indicators,and inhibiting liver cell apoptosis.
作者
陈新
牟雄军
刘昊
刘焱文
刘松林
CHEN Xin;MOU Xiong-jun;LIU Hao;LIU Yan-wen;LIU Song-lin(Hubei Provincial Key L aboratory for Resource and Chemistry of Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第18期18-23,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
湖北省教育厅科学技术研究项目(Q20182009)。
关键词
加味四逆散
抑郁模型
肝损伤
肝功能
炎症因子
细胞凋亡
modified Sinisan
depressive model
liver injury
liver function
inflammatory factor
cell apoptosis