扶正化瘀胶囊、一贯煎和茵陈蒿汤对刀豆蛋白A诱导大鼠肝纤维化的作用比较OA
Comparative Study on the Effects of Fuzheng Huayu Capsule,Yiguanjian,and Yinchenhao Decoction on Concanavalin A-Induced Hepatic Fibrosis in Rats
目的:探讨扶正化瘀胶囊、一贯煎与茵陈蒿汤对刀豆蛋白A(concanavalin A,ConA)诱导肝纤维化(hepatic fibrosis,HF)大鼠的作用机制.方法:将53只Wistar大鼠随机分为正常组(10只)与造模组,除正常组大鼠外,其余大鼠经尾静脉注射ConA复制HF动物模型,造模成功后,将造模大鼠随机分为模型组、扶正化瘀胶囊组(以下简称扶正化瘀组)、一贯煎组及茵陈蒿汤组.正常组与模型组灌胃饮用水,一贯煎组、茵陈蒿汤组、扶正化瘀组对应灌胃药物剂量分别为7.58 g·kg-1、5.13 g·kg-1、0.525 g·kg-1,持续干预4周.观察大鼠造模期间及干预期间体质量及肝脏指数变化情况;检测各组大鼠血清天冬氨酸氨基转移酶(aspar-tate aminotransferase,AST)、丙氨酸氨基转移酶(alanine transaminase,ALT)、透明质酸(hyaluronic acid,HA)、层粘连蛋白(laminin,LN)、Ⅲ型前胶原(rat procollagen Ⅲ,PC Ⅲ)、Ⅳ型胶原(collagen type,C-Ⅳ)、α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、基质金属蛋白酶1(matrix metalloprotein-ase-1,MMP-1)、基质金属蛋白酶抑制因子1(tissue inhibitor of metalloproteinase-1,TIMP-1)水平及肝组织羟脯氨酸(hydroxyproline,Hyp)含量;观察各组大鼠肝组织形态学变化情况.结果:造模期间,模型组大鼠体质量增长低于正常组(P<0.01);干预期间,各组大鼠体质量均增加,但组间比较差异无统计学意义(P>0.05);各组大鼠肝脏指数比较差异无统计学意义(P>0.05).与正常组比较,模型组大鼠血清AST、ALT、Hyp、HA、LN、PC Ⅲ、C-Ⅳ、α-SMA、TIMP-1表达水平均升高(P<0.01),MMP-1及MMP-1/TIMP-1均降低(P<0.01);与模型组比较,扶正化瘀组、一贯煎组、茵陈蒿汤组大鼠以上指标表达水平均改善(P<0.05,P<0.01).各干预组大鼠肝组织病理形态得到不同程度改善,肝细胞排列较整齐,细胞变形坏死减少,部分肝小叶结构完整,纤维组织增生较模型组改善.结论:扶正化瘀胶囊、一贯煎、茵陈蒿汤均能改善ConA诱导的免疫性HF大鼠肝功能及HF指标,其作用机制可能与抑制肝星状细胞活化,促进MMP/TIMP平衡有关.
Objective:To investigate the mechanisms of action of Fuzheng Huayu capsule,Yiguanjian,and Yinchenhao decoction on concanavalin A(Con A)-induced hepatic fibrosis(HF)in rats.Methods:A total of 53 Wistar rats were randomly divided into a normal control group(n=10)and a model induction group.Except for those in the normal control group,all rats received tail vein injection of Con A to establish the HF animal model.After successful model establishment,the model rats were randomly divided into the model group,Fuzheng Huayu capsule group(hereinafter referred to as the Fuzheng Huayu group),Yiguanjian group,and Yinchenhao decoction group.The normal and model groups received distilled water via intragastric gavage,whereas the Yiguanjian,Yinchenhao decoction,and Fuzheng Huayu groups were treated with corresponding drug solutions at doses of 7.58 g·kg⁻¹,5.13 g·kg⁻¹,and 0.525 g·kg⁻¹,respectively,for four consecutive weeks.Body weight and liver index were recorded throughout the modeling and treatment periods.Serum biochemical parameters,including aspartate aminotransferase(AST),alanine transaminase(ALT),hyaluronic acid(HA),laminin(LN),procollagen type Ⅲ(PC Ⅲ),collagen type Ⅳ(C-Ⅳ),α-smooth muscle actin(α-SMA),matrix metalloproteinase-1(MMP-1),and tissue inhibitor of metalloproteinase-1(TIMP-1),together with hepatic hydroxyproline(Hyp)content,were determined for all groups.Liver tissue morphology was observed and compared among all groups.Results:During the modeling period,the body weight gain of rats in the model group was significantly lower than that in the normal control group(P<0.01).During the intervention period,body weight increased in all groups,but there was no statistically significant difference among the groups(P>0.05).No statistically significant difference was observed in liver index among the groups(P>0.05).In comparison with the normal control group,serum levels of AST,ALT,Hyp,HA,LN,PC Ⅲ,C-Ⅳ,α-SMA,and TIMP-1 were significantly increased in the model group(P<0.01),whereas MMP-1 level and the MMP-1/TIMP-1 ratio were significantly decreased(P<0.01).In comparison with the model group,all three treatment groups(Fuzheng Huayu,Yiguanjian,and Yinchenhao decoction)showed significant amelioration of the aforementioned indicators(P<0.05,P<0.01).Liver histopathology showed varying degrees of improvement in all treatment groups.Hepatocytes were arranged in a more orderly manner,with less cellular deformity and necrosis.Some hepatic lobules retained relatively intact architecture,and fibrous tissue hyperplasia was attenuated compared with the model group.Conclusion:Fuzheng Huayu Capsule,Yiguanjian,and Yinchenhao decoction all attenuated liver dysfunction and HF indices in Con A-induced immunological HF rats,possibly through inhibiting hepatic stellate cell activation and restoring the MMP/TIMP balance.
李佳潞;李涵;李孝波;郝瑞春
山西中医药大学,山西 晋中 030619山西中医药大学,山西 晋中 030619山西中医药大学,山西 晋中 030619山西中医药大学,山西 晋中 030619
医药卫生
肝纤维化刀豆蛋白A扶正化瘀胶囊一贯煎茵陈蒿汤
hepatic fibrosisconcanavalin AFuzheng Huayu capsuleYiguanjianYinchenhao decoction
《西部中医药》 2026 (10)
9-14,6
山西省自然科学基金项目(201901D111337)山西省中医药管理局科研计划项目(2024ZYYC060).
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