基于IKKβ/NF-κB通路研究芪甲柔肝方抗肝纤维化作用机制  

Study on the mechanism of Qijia Rougan Prescription in anti-hepatic fibrosis based on IKKβ/NF-κB pathway

作　　者：姜岑[1] 宋虹霏 王东[1] 刘文平 苏悦[1] 冯全生[1] JIANG Cen;SONG Hong-fei;WANG Dong;LIU Wen-ping;SU Yue;FENG Quan-sheng(Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China)

机构地区：[1]成都中医药大学,成都610075

出　　处：《中华中医药杂志》2022年第8期4805-4809,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：四川省科技计划重点研发项目(No.2020YFS0301)。

摘　　要：目的:研究芪甲柔肝方改善肝纤维化可能机制。方法:将68只SPF级雄性SD大鼠随机分为空白组(10只)和造模组(58只)。造模组采用皮下注射CCl4花生油+10%乙醇代水饮的方式建立肝纤维化模型。造模成功后,将造模组大鼠随机分为模型组、芪甲柔肝组、鳖甲煎丸组,各组分别予相应药液灌胃,每日1次,连续6周。HE染色和Masson染色观察大鼠肝组织病理学及胶原沉积情况;全自动血清生化仪检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、碱性磷酸酶(ALP)的表达水平;酶联免疫吸附法测定血清肿瘤坏死因子-α(TNF-α)表达情况;免疫组化法检测肝组织α平滑肌肌动蛋白(α-SMA)、核转录因子p65(NF-κB p65)、IκB激酶β(IKKβ)蛋白表达水平。结果:与空白组比较,模型组大鼠AST、ALT、ALP和TNF-α水平显著升高(P<0.05),病理见模型组肝细胞排列紊乱,大量纤维纵隔、假小叶生成,α-SMA、NF-κB p65和IKKβ蛋白表达显著升高(P<0.05);与模型组比较,芪甲柔肝组和鳖甲煎丸组大鼠AST、ALT、ALP和TNF-α水平显著降低(P<0.05),α-SMA、NF-κB p65和IKKβ蛋白表达显著降低(P<0.05)。上述病理均有改善。结论:芪甲柔肝方具有改善肝损伤、抗炎及抗纤维化的作用,这可能与抑制IKKβ/NF-κB信号通路激活有关。Objective:To study the possible mechanism of Qijia Rougan Prescription in improving liver fibrosis.Methods:Sixty-eight SPF male SD rats were randomly divided into the blank group(n=10) and model group(n=58).The model group was established by subcutaneous injection of carbon tetrachloride(CCl4) peanut oil+10% ethanol instead of water,and then they were randomly divided into the model group,Qijia Rougan group,and Biejia Jianwan group.Each group was given the corresponding drug solution by gavage once a day for 6 weeks.HE staining and Masson staining were used to observe the histopathology and collagen deposition in rat liver.The expression levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT) and alkaline phosphatase(ALP) were detected by an automatic serum biochemical analyzer.The expression of serum tumour necrosis factor-α(TNF-α) was detected by enzyme-linked immunosorbent assay;the expression of smooth muscle alpha-actin(α-SMA),nuclear factor-κB p65(NF-κB p65),and inhibitor kappa B kinase β(IKKβ) in liver tissue was detected by immunohistochemistry.Results:Compared with the blank group,the levels of AST,ALT,ALP and TNF-α in the model group were significantly increased(P<0.05).The pathology of the model group showed that the arrangement of hepatocytes was disordered,and a large number of fibrous mediastinum and pseudolobules were formed.The protein expressions of α-SMA,NF-κB p65 and IKKβ were significantly increased(P<0.05);Compared with the model group,the levels of AST,ALT,ALP and TNF-α in Qijia Rougan group and Biejia Jianwan group were significantly decreased(P<0.05),and the protein expressions of α-SMA,NF-κB p65 and IKKβ were significantly decreased(P<0.05).The above pathologies were improved.Conclusion:Qijia Rougan Prescription can improve liver injury,and anti-inflammatory and anti-fibrosis,which may be related to inhibiting the activation of IKKβ/NF-κB signalling pathway.

关 键 词：肝纤维化 四氯化碳 芪甲柔肝方 IKKβ/NF-κB通路 气血理论 

分 类 号：R285.5[医药卫生—中药学]