文献类型：期刊文献

中文题名：化瘀软肝胶囊对四氯化碳诱导肝纤维化大鼠的作用

英文题名：Effects of Huayu Ruangan Capsules on CCl_(4)-induced hepatic fibrosis in rats

作者：胥文娟[1,2];李红芳[3];牛媛媛[1];毛兰芳[4];杜晓娟[1];李正菊[1];张萍[1];陶永彪[1];汪龙德[4]

第一作者：胥文娟

机构：[1]甘肃中医药大学,甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000;[2]甘肃省中医院,甘肃兰州730050;[3]兰州大学,甘肃兰州730000;[4]甘肃中医药大学附属医院,甘肃兰州730020

第一机构：甘肃中医药大学科研实验中心（甘肃省中医药标准化技术委员会秘书处）

年份：2023

卷号：45

期号：5

起止页码：1447

中文期刊名：中成药

外文期刊名：Chinese Traditional Patent Medicine

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金项目(82160883);甘肃省科技计划项目(21JR11RA210);兰州市城关区科学技术局课题(2021-9-2);甘肃省中医药研究中心开放课题资助(zyzx-2020-02);敦煌医学与转化教育部重点实验室开放基金(DHYX18-27)。

语种：中文

中文关键词：化瘀软肝胶囊;肝纤维化;CCl_(4);Wnt/β-catenin信号通路

外文关键词：Huayu Ruangan Capsules;liver fibrosis;CCl_(4);Wnt/β-catenin signaling pathway

摘要：目的探讨化瘀软肝胶囊对肝纤维化大鼠的作用以及对肝组织Wnt/β-catenin信号通路的影响。方法将60只大鼠随机分为正常组(10只)和造模组(50只),造模组以CCl_(4)复合因素造模6周后,随机分为模型组、秋水仙碱组(0.2 mg/kg)和化瘀软肝胶囊低、中、高剂量组(0.27、0.54、1.08 g/kg),各组以相应的药物或生理盐水灌胃6周,每天2次。HE和Masson染色观察大鼠肝组织病理改变,生化法和化学发光法分别检测大鼠血清肝功能(ALT、AST、TG、TBIL)和肝纤维化指标(HA、LN、PC-Ⅲ、Ⅳ-C),RT-qPCR和Western blot法检测大鼠肝组织Wnt1、Wnt3a、Wnt10、GSK-3β、β-catenin、c-Myc mRNA和蛋白表达,免疫荧光法检测大鼠肝组织β-catenin和α-SMA蛋白表达。结果与正常组比较,模型组肝组织病理损伤,血清ALT、AST、TG、TBIL、HA、LN、PC-Ⅲ、Ⅳ-C水平升高(P<0.01),肝组织Wnt1、Wnt3a、Wnt10、β-catenin、c-Myc mRNA和蛋白表达升高(P<0.01),GSK-3βmRNA和蛋白表达降低(P<0.01),免疫荧光显示肝组织α-SMA和β-catenin蛋白表达增强(P<0.01);与模型组比较,化瘀软肝胶囊各剂量组可不同程度地改善肝组织病理变化,减弱α-SMA荧光强度,恢复血清肝功能和肝纤维化指标(P<0.05,P<0.01),降低Wnt1、Wnt3a、Wnt10、β-catenin、c-Myc mRNA和蛋白表达(P<0.05,P<0.01),升高GSK-3βmRNA和蛋白表达(P<0.05,P<0.01)。结论化瘀软肝胶囊可减轻大鼠肝纤维化程度,其机制可能与调节Wnt/β-catenin信号通路中相关基因和蛋白的表达有关。
AIM To investigate the effects of Huayu Ruangan Capsules on hepatic fibrosis and its influence on Wnt/β-catenin signaling pathway in liver tissue of rats.METHODS In contrast to the 10 rats randomly assigned into the normal group,the other 50 rats were induced into hepatic fibrosis models with 6 weeks administration of CCl_(4),and further divided into the model group for colchicine group(0.2 mg/kg)and the low,medium and high dose groups of Huayu Ruangan Capsules(0.27,0.54 and 1.08 g/kg),6 weeks intragastrical dosing of corresponding drug or saline water(twice daily).The rats had their liver pathological changes observed by HE and Masson staining;their serum liver function(ALT,AST,TG,TBIL)and liver fibrosis indexes levels(HA,LN,PC-III,Ⅳ-C)assessed by biochemical method and chemiluminescence method;their mRNA and protein expressions of Wnt1,Wnt3a,Wnt10,GSK-3β,β-catenin and c-Myc detected by RT-qPCR and Western blot;and their hepatic expressions ofβ-catenin andα-SMA protein detected by immunofluorescence.RESULTS Compared with the normal group,the model group was observed with pathological hepatic damage;increased levels of serum ALT,AST,TG,TBIL,HA,LN,PC-ⅢandⅣ-C(P<0.01);enhanced mRNA and protein expressions of Wnt1,Wnt3a,Wnt10,β-catenin and c-Myc(P<0.01);and decreased mRNA and protein expression of GSK-3β(P<0.01),in addition to the up-regulated hepatic protein expressions ofα-SMA andβ-catenin revealed by the result of immunofluorescence(P<0.01).Compared with the model group,the Huayu Ruangan Capsules groups shared differently improved pathological hepatic changes,weakened fluorescence intensity ofα-SMA,restored serum liver function and liver fibrosis indicators levels(P<0.05,P<0.01),reduced mRNA and protein expressions of Wnt1,Wnt3a,Wnt10,β-catenin,and c-Myc(P<0.05,P<0.01),and increased mRNA and protein expression of GSK-3β(P<0.05,P<0.01).CONCLUSION Huayu Ruangan Capsules can reduce the degree of liver fibrosis in rats,and its mechanism may associate with the regulations on the expressions of related genes and proteins in Wnt/β-catenin signaling pathway.