清化瘀毒方对酒精-四氯化碳诱导肝纤维化小鼠的治疗作用及机制探索  

Mechanism investigation of Qinghua Yudu Prescription on alcohol-CCl_(4)induced liverfibrosismice

作　　者：胡紫怡 沈佳璐 乐翊飞 蒋飘艺 王邦才 李松涛 陈林 窦晓兵[1] HU Ziyi;SHEN Jialu;LE Yifei;JIANG Piaoyi;WANG Bangcai;LI Songtao;CHEN Lin;DOU Xiaobing(College of Life Science,Zhejiang Chinese Medical University,Hangzhou 310053,China;Ningbo Hospital of Traditional Chinese Medicine,Ningbo 315010,China;College of Basic Medicine&Public Health,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学生命科学学院,杭州310053 [2]宁波市中医院,宁波315010 [3]浙江中医药大学公共卫生学院,杭州310053

出　　处：《中华中医药杂志》2023年第8期3600-3604,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：浙江省自然科学基金重点项目(No.LZ21H030001);浙江省教育厅科研项目(No.Y202146164);浙江中医药大学校级科研项目(No.2021ZZ06)。

摘　　要：目的:探索清化瘀毒方改善酒精-四氯化碳诱导的肝纤维化小鼠的治疗作用和相关机制。方法:将60只C57BL/6J小鼠随机分为对照组,中药组,模型组,清化瘀毒方低、高浓度治疗组和阳性组,每组各10只,建立肝纤维化模型。自第5周起给予药物治疗,持续4周。分析肝组织内纤维化标志蛋白α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(Col1α1)的表达和肝组织病理变化,验证本方的疗效。通过UPLC-Q/TOF-MS获取本方的有效成分,并利用网络药理学预测作用靶点,验证、分析清化瘀毒方发挥治疗作用的相关靶点。结果:清化瘀毒方可能通过下调凋亡信号调控激酶1(ASK1)/p38丝裂原活化蛋白激酶(p38 MAPK)、Toll样受体4(TLR4)/髓样分化因子(MyD88)、B淋巴细胞瘤2(BCl-2)关联X蛋白(BAX)/BCl-2等蛋白表达,影响肝组织Col1α1、α-SMA的表达水平,减轻酒精-四氯化碳诱导的小鼠肝纤维化。结论:清化瘀毒方可通过ASK1/p38 MAPK、TLR4/MyD88等机制通路发挥作用,减轻肝脏纤维化。Objective:To investigate the therapeutic effects and related mechanisms of Qinghua Yudu Prescription on alcohol-CCl4 induced liver fibrosis in mice.Methods:Sixty C57BL/6J mice were randomly divided into control group,traditional Chinese medicine group,model group,low and high concentration QinghuaYudu Prescription treatment group and positive group,with 10 mice in each group,to establish liver fibrosis model.Medication was given from the fifth week for 4 weeks.To analyze the expression of fibrosis marker proteinα-smooth muscle actin(α-SMA)and collagen type I alpha 1 chain(Collal)in liver tissue and the pathological changes of liver tissue,and verify the curative effect of this prescription.The effective components of this prescription were obtained by UPLC-Q/TOF-MS,and the target of action was predicted by network pharmacology to verify and analyze the related targets of the therapeutic effect of Qinghua Yudu Prescription.Results:Qinghua Yudu Prescription might affect the expression of Collal andα-SMA in liver tissue by down-regulating the expression of apoptosis signal regulating kinase-1(ASK1)/p38 mitogen activated protein kinase(p38 MAPK),Toll-like receptor 4(TLR4)/myeloid differentiation factor(MyD88)and B-lymphocyte tumor 2(BCI-2)/BCI-2 associated X protein(BAX).Conclusion:Qinghua Yudu Prescription can relieve liver fibrosis through ASK1/p38 MAPK and TLR4/MyD88 pathways.

关 键 词：清化瘀毒方 肝纤维化 网络药理学 多机制通路 

分 类 号：R285.5[医药卫生—中药学]