汉黄芩素通过调节Hedgehog-YAP信号通路减轻肝硬化大鼠的肝纤维化  

Wogonin reduces the degree of fibrosis in cirrhotic rats by regulating Hedgehog-YAP signal pathway

作　　者：瞿旖妮 辛晓丽[2] 周慧君[1] Qu Yini;Xin Xiaoli;Zhou Huijun(Pharmacy Department,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Department of Oncology,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院药剂科,上海200032 [2]上海中医药大学附属龙华医院肿瘤二科,上海200032

出　　处：《解剖学杂志》2024年第1期35-39,80,共6页Chinese Journal of Anatomy

摘　　要：目的:探讨汉黄芩素(Wog)对肝纤维化模型大鼠的影响及其机制。方法:将大鼠分为对照组,模型组,Cym组(Hedgehog抑制剂组),Wog低、中、高剂量组。检测各组大鼠血清肝功能指标丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、谷氨酰转肽酶(GGT)水平,肝纤维化指标透明质酸(HA)、Ⅳ型胶原(CⅣ)、层黏蛋白(LN)、Ⅲ型前胶原(PCⅢ)水平;天狼星红染色观察肝组织胶原纤维;RT-qPCR法检测肝组织Ⅰ型胶原(ColⅠ)、α-肌动蛋白(α-SMA)mRNA水平;检测肝组织羟脯氨酸(Hyp)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平;免疫印迹检测Hedgehog-YAP通路相关蛋白SMO、GLI2、SHH、Yes相关蛋白1(YAP)、p-YAP水平。结果:与对照组相比,模型组血清ALT、AST、GGT、HA、CⅣ、LN、PCⅢ水平和肝组织ColⅠ、α-SMA mRNA、Hyp、MDA、SMO、GLI2、SHH、p-YAP/YAP水平均升高,SOD水平降低;与模型组相比,Cym组和Wog低、中、高剂量组血清ALT、AST、GGT、HA、CⅣ、LN、PCⅢ水平和肝组织ColⅠ、α-SMA mRNA、Hyp、MDA、SMO、GLI2、SHH、p-YAP/YAP水平均降低,SOD水平均升高;其中Cym组与Wog高剂量组相比,上述指标无显著差异。对照组肝组织未见增生的纤维组织,模型组肝组织胶原纤维增生明显,胶原染色面积增大;与模型组相比,Cym组和Wog低、中、高剂量组肝组织胶原纤维增生程度均减轻,胶原染色面积减小;其中Cym组与Wog高剂量组相比,胶原纤维增生程度无显著差异。结论:Wog可减轻肝纤维化模型大鼠肝纤维化程度,对肝纤维化模型大鼠具有保护作用,其机制可能与Wog可抑制Hedgehog-YAP信号通路有关。Objective:To investigate the influence of Wogonin(Wog)on the degree of fibrosis in cirrhotic rats and its mechanism.Methods:The rats were divided into the control group,model group,Cym group(Hedgehog inhibitor group),and low,medium and high dose Wog group.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl transpeptidase(GGT),hyaluronic acid(HA),collagen typeⅣ(CⅣ),laminin(LN)and procollagen type III(PCⅢ)were measured.Sirius red staining was used to observe the pathological morphology and degree of liver fibrosis.RT-qPCR was used to detect the expression of collagenⅠ(ColⅠ)andα-actin(α-SMA)in liver tissues.The activities of hydroxyproline(Hyp),superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tissues were measured,and the expression levels of SMO,GLI2,SHH,YAP and p-YAP related proteins in Hedgehog-YAP pathway were detected by Western blotting.Results:Compared with the control group,the activities of ALT,AST,GGT,the contents of HA,CⅣ,LN and PCⅢin serum,and the levels of ColⅠandα-SMA mRNA,the contents of Hyp and MDA,and the expression of SMO,GLI2,SHH,and p-YAP/YAP in the model group were increased,while the activity of SOD in the model group was decreased.Compared with the model group,the activities of ALT,AST,GGT,the contents of HA,CⅣ,LN and PCⅢin serum,and the levels of ColⅠandα-SMA mRNA,the contents of Hyp and MDA,and the expression of SMO,GLI2,SHH,and p-YAP/YAP were reduced,and SOD levels were increased in the Cym and low,medium,and high-dose Wog groups.There was no significant difference in the above indicators between the Cym group and the high-dose Wog group.The liver tissue of the control group did not show an increase in fibrous tissue proliferation,while the liver tissue of the model group showed obvious collagenfiber proliferation and an increase in collagen staining area.Compared with the model group,the degree of collagenfiber proliferation in the liver tissue of the Cym and low,medium,and high-dose Wog groups was reduced,and the

关 键 词：汉黄芩素 Hedgehog-YAP信号通路 肝硬化 肝纤维化 肝功能 胶原纤维 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学]