【目的】观察化浊解毒调肝方对肝纤维化大鼠的治疗作用及机制。 【方法】 将60只大鼠随机分为正常组，模型组，中药低、中、高剂量组及西药组。每组10只。除正常组外，其余各组大鼠均构建肝纤维化模型。建模成功后，中药低、中、高剂量组大鼠给予化浊解毒调肝方水煎剂灌胃，西药组给予秋水仙碱灌胃。给药28 d后，全自动生化分析仪检测血清肝功能指标丙氨酸氨基转氨酶 （ALT） 、天门冬氨酸氨基转移酶 （AST） 和碱性磷酸酶 （ALP） 水平，苏木素-伊红 （HE） 染色法观察肝组织病理形态，马松 （Masson） 染色法观察肝组织胶原沉积，采用酶联免疫吸附分析 （ELISA） 法检测肝组织中脂质过氧化指标超氧化物歧化酶 （SOD） 、谷胱甘肽过氧化物酶 （GSH-Px） 、丙二醛 （MDA） 、过氧化氢酶 （CAT） 水平，免疫组织化学法检测肝组织巨噬细胞表面标志物M2型分化抗原簇163 （CD163） 、M1型分化抗原簇68 （CD68） 阳性表达，Western Blot法检测肝组织中C-C基序趋化因子22 （CCL22） 、CC趋化因子受体4 （CCR4） 蛋白表达。 【结果】与正常组比较，模型组大鼠血清ALT、AST及LP等肝功能指标水平升高，肝组织SOD、GSH-Px、CAT水平降低及MDA水平升高，肝组织CD163阳性表达水平降低及D68阳性表达水平升高，肝组织CCL22、CCR4蛋白表达水平升高，差异均有统计学意义 （P＜0.05） ；与模型组比较，中药低、中、高剂量组及西药组血清ALT、AST及ALP水平降低，SOD、GSH-Px、CAT水平升高及MDA水平降低，CD163阳性表达水平升高及CD68阳性表达水平降低，CCL22、CCR4蛋白表达水平降低，差异均有统计学意义 （P＜0.05） ；中药高剂量组上述各指标 （除ALT、ALP） 水平与西药组比较，差异无统计学意义 （P＞0.05） 。 【结论】化浊解毒调肝方抗肝纤维化机制与抑制脂质过氧化，加快M1型巨噬细胞向M2型转变，及抑制CCL22/CCR4活性有关。

Objective To observe the therapeutic efficacy and mechanism of Huazhuo Jiedu Tiaogan Prescription in rats with hepatic fibrosis（HF） . Methods Sixty rats were randomly divided into normal group，model group，Chinese medicine low-，medium- and high- dose groups，and western medicine group，10 rats in each group. Except for the normal group，the rats in all groups were established HF model. After successful modeling，the rats in Chinese medicine low-，medium- and high- dose groups were given gastric administration of water decoction of Huazhuo Jiedu Tiaogan Prescription，and the rats in western medicine group were given gastric administration of colchicine saline solution. After 28-day administration，the serum levels of alanine aminotransferase（ALT），aspartate aminotransferase（AST） and alkaline phosphatase（ALP） were measured by an automatic biochemical analyzer， the pathological morphology of the liver tissues was observed by hematoxylin-eosin（HE） staining method，and collagen deposition of the liver tissues was detected by Masson staining，and the levels of lipid peroxidation indicators in liver tissues such as superoxide dismutase （SOD） ，glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） and catalase （CAT） were detected by enzyme-linked immunosorbent assay （ELISA） ，and the positive expression of M2-type cluster of differentiation 163（CD163），M1-type cluster of differentiation 68（CD68） ，which are macrophage surface markers in liver tissues，were detected by immunohistochemical assay，Western Blot method was used to detect the protein expression of C-C motif chemokine 22（CCL22） and CC chemokine receptor 4 （CCR4） in liver tissues. Results Compared with the normal group，the levels of liver function indicators including ALT，AST and ALP in rat serum were elevated in the model group，the levels of SOD，GSH-Px and CAT in liver tissues were decreased and level of MDA was decreased，the level of CD163 positive expression was decreased and level of CD68 positive expression was increased in liver tissues，and the protein expression levels of CCL22 and CCR4 were elevated in liver tissues，the differences being all statistically significant （P＜0.05） .Compared with the model group，the levels of serum ALT，AST and ALP in the Chinese medicine low-，medium- and high-dose groups as well as the western medicine group were decreased，the levels of liver tissue SOD，GSH-Px and CAT were increased，and MDA level was decreased，liver tissue CD163 positive expression level was increased and CD68 positive expression level was decreased， and the protein expression levels of CCL22 and CCR4 in liver tissues were decreased，differences being statistically significant （P＜0.05） . The levels of the above indicators （except for ALT and ALP） in the high-dose of Chinese medicine group showed that the differences was not statistically significant compared with those in the western medicine group（P＞0.05） .Conclusion The anti-fibrosis effect of Huazhuo Jiedu Tiaogan Prescription is related to the inhibition of lipid peroxidation，accelerating the transformation of M1-type macrophages to M2-type，and the inhibition of CCL22/CCR4 expression.

R285.5

河北省中医药管理局科研基金资助项目 （编号：2022327）