文献类型：期刊文献

中文题名：慈菇消脂方通过抑制Hedgehog信号通路激活缓解非酒精性脂肪性肝炎肝纤维化

英文题名：Cigu Xiaozhi Prescription Alleviates NASH Liver Fibrosis by Inhibiting the Activation of the Hedgehog Signaling Pathway

作者：任真[1];杨咏嘉[2];郭才[3];张钰洁[2];马燕花[2]

第一作者：任真

机构：[1]甘肃中医药大学医学信息工程学院,甘肃兰州730000;[2]甘肃中医药大学第一临床医学院,甘肃兰州730000;[3]鄂州市中心医院消化内科,湖北鄂州436000

第一机构：甘肃中医药大学信息工程学院（教育技术中心）

年份：2025

卷号：41

期号：7

起止页码：936

中文期刊名：南京中医药大学学报

外文期刊名：Journal of Nanjing University of Traditional Chinese Medicine

收录：;北大核心:【北大核心2023】；

基金：甘肃省联合科研基金一般项目(23JRRA1523);兰州市科技计划项目(2023-2-84)。

语种：中文

中文关键词：非酒精性脂肪性肝炎;肝纤维化;Hedgehog信号通路;慈菇消脂方;肝星状细胞

外文关键词：non-alcoholic steatohepatitis;liver fibrosis;Hedgehog signaling pathway;Cigu Xiaozhi Prescription;hepatic stellate cells

摘要：目的探究慈菇消脂方(Cigu Xiaozhi Prescription,CGXP)治疗非酒精性脂肪性肝炎(Non-Alcoholic steatohepatitis,NASH)肝纤维化的潜在机制。方法建立了NASH小鼠模型,并通过计算肝脏指数来评估肝脏肿大程度,同时利用HE和Masson染色法观察肝纤维化程度。此外,免疫组化法检测肝纤维化相关蛋白α-SMA、Collagen 1、MMP2和MMP9蛋白表达情况。通过Western blot和qPCR技术检测小鼠肝脏中HIF-1α、E-cadherin、N-cadherin、Shh、Smo、Gli1和Gli2的表达水平,并使用碱水法测定了肝脏羟脯氨酸(Hyp)含量。结果高剂量的CGXP能够有效降低肝脏指数(P<0.001),减轻肝脏肿大和炎症,显著改善肝纤维化小鼠的肝组织病理损伤。CGXP显著降低了肝纤维化相关蛋白α-SMA、Collagen 1、MMP2和MMP9蛋白表达水平(P<0.01,P<0.0001);降低HIF-1α、E-cadherin、N-cadherin、Shh、Smo、Gli1和Gli2的水平,其中高剂量CGXP的治疗效果尤为显著(P<0.05,P<0.01,P<0.001,P<0.0001)。结论CGXP可能通过抑制Hedgehog信号通路改变了肝星状细胞(Hepatic stellate cells,HSCs)的活化与增殖,减少了细胞外基质的合成与沉积,缓解NASH小鼠肝纤维化。
OBJECTIVE To explore the potential mechanism of Cigu Xiaozhi Prescription(CGXP)in the treatment of non-alcoholic steatohepatitis(NASH)liver fibrosis.METHODS A NASH mouse model was established.The degree of liver enlargement was evaluated by calculating the liver index.Hematoxylin-eosin(HE)and Masson staining were used to observe the degree of liver fibrosis.In addition,immunohistochemistry was employed to detect the expression of liver fibrosis-related proteins,includingα-SMA,Collagen 1,MMP2,and MMP9.Western blot and qPCR techniques were used to detect the expression levels of HIF-1α,E-cadherin,N-cadherin,Shh,Smo,Gli1,and Gli2 in the mouse liver.The alkaline hydrolysis method was used to measure the content of liver hydroxyproline.RESULTS CGXP could effectively reduce the liver index(P<0.001),alleviate liver enlargement and inflammation,and significantly improve the pathological damage of liver tissue in mice with liver fibrosis.CGXP significantly decreased the expression levels of liver fibrosis-related proteinsα-SMA,Collagen 1,MMP2 and MMP9(P<0.01,P<0.0001);reduced the levels of HIF-1α,E-cadherin,N-cadherin,Shh,Smo,Gli1,and Gli2,and the therapeutic effect of high-dose CGXP was particularly significant(P<0.05,P<0.01,P<0.001,P<0.0001).CONCLUSION CGXP can relieve NASH liver fibrosis in mice by reducing the liver index,alleviating inflammation,and improving tissue pathological damage.The mechanism may be related to the inhibition of the Hedgehog signaling pathway,which alters the activation and proliferation of hepatic stellate cells and reduces the synthesis and deposition of extracellular matrix.