异甘草素对大鼠肝纤维化的治疗作用及其机制  

Therapeutic effect of isoliquiritigenin on rat hepatic fibrosis and its mechanism

作　　者：张畦 安祯祥 何远利 Zhang Qi;An Zhenxiang;He Yuanli(The First Clinical Medical College of Guizhou University of Traditional Chinese Medicine,Guiyang 550002;Dept of Gastroenterology,The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001;Dept of Geriatrics,The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001)

机构地区：[1]贵州中医药大学第一临床医学院,贵阳55000 [2]贵州中医药大学第一附属医院消化内科,贵阳550001 [3]贵州中医药大学第一附属医院老年病科,贵阳550001

出　　处：《安徽医科大学学报》2023年第4期649-654,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82160893、81760865);国家中医药管理局第五批全国中医临床优秀人才研修项目(编号:国中医药人教函[2022]1号)。

摘　　要：目的 探讨异甘草素(ISL)对肝纤维化(HF)的治疗作用及其机制。方法 将45只SD大鼠随机分为正常组、模型组、秋水仙碱组(阳性对照,0.1 mg/kg)、ISL高、低剂量组(ISL 40、10 mg/kg)。除正常组外,其余各组采用50%四氯化碳(CCl4)橄榄油溶液(1.5 ml/kg)腹腔注射建立HF模型,每周2次,持续8周。造模结束后各组大鼠按照每天10 ml/kg灌胃相应药物,共4周。末次给药后,测定大鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)含量;计算肝脏指数;HE及Masson染色观察肝组织病理变化;实时荧光定量PCR检测低氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)的mRNA表达水平;免疫组化、Western blot检测肝组织中HIF-1α、VEGF蛋白的表达情况。结果 与正常组相比:模型组大鼠血清中ALT、AST含量上升(P<0.01),肝脏指数升高(P<0.01),大鼠纤维组织增生,胶原容积分数增加(P<0.01),肝组织内HIF-1α、VEGF mRNA表达水平上升(P<0.01);免疫组化及Western blot检测均表明模型组HIF-1α、VEGF蛋白表达水平上升(P<0.01)。与模型组相比:ISL高、低剂量组血清中ALT、AST水平降低(P<0.01),肝脏指数下降(P<0.01),纤维化组织增生减轻,胶原容积分数下降(P<0.05),HIF-1α、VEGF基因表达水平下调(P<0.01);免疫组化检测表明ISL高、低剂量组HIF-1α蛋白水平降低(P<0.01,P<0.05),VEGF蛋白表达水平降低(P<0.01);Western blot检测表明ISL高剂量组HIF-1α、VEGF蛋白表达水平降低(P<0.05)。结论 ISL对CCl4诱导HF模型大鼠有显著的治疗效果,其作用机制可能与调节HIF-1α、VEGF蛋白表达水平有关。Objective To investigate the therapeutic effect and mechanism of isoliquiritigenin(ISL)on hepatic fibrosis(HF).Methods SD rats were randomly divided into normal group,model group,colchicine tablet group(positive control,0.1 mg/kg),and high-dose and low-dose ISL groups(40,10 mg/kg).Except for the normal group,the other groups were given intraperitoneal injection of 50%carbon tetrachloride(CCl 4)olive oil solution(1.5 ml/kg)to establish liver fibrosis models,twice a week for 8 weeks.After modeling,rats in each group were given the corresponding drugs by gavage at a volume of 10 ml/kg per day for 4 weeks.After the last administration,the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the serum of rats were determined;liver index was calculated;HE and Masson staining were used to observe the pathological changes of liver tissue;Real-time quantitative PCR was used to detect the mRNA expression levels of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF);the expressions of HIF-1αand VEGF protein in liver tissue were detected by immunohistochemistry and Western blot.Results Compared with the normal group,the serum ALT and AST contents of the rats in the model group increased(P<0.01),the liver index increased(P<0.01),the rat fibrous tissue hyperplasia,the collagen volume fraction increased(P<0.01),and the liver the expression levels of HIF-1αand VEGF mRNA in the tissue increased(P<0.01).Immunohistochemistry and Western blot showed that the expression levels of HIF-1αand VEGF protein increased in the model group(P<0.01).Compared with the model group,the ISL high and low dose groups could reduce the levels of ALT and AST in serum(P<0.01),the liver index(P<0.01),the proliferation of fibrotic tissue and the collagen volume fraction(P<0.05),down-regulate the expression levels of HIF-1αand VEGF genes(P<0.01).Immunohistochemical detection showed that the high and low dose groups of ISL could reduce the protein expression levels of HIF-1α(P<0.01,P<0.05),the expres

关 键 词：肝纤维化 低氧诱导因子-1Α 血管内皮生长因子 异甘草素 

分 类 号：R256.42[医药卫生—中医内科学]