大麻二酚对转化生长因子β1诱导肝星状细胞活化和肝纤维化的作用  

Effects of cannabidiol on hepatic stellate cell activation and hepatic fibrosis induced by transforming growth factor beta1

作　　者：王联 谢娜 赵珮伶 陈浩 李芏酉 王豫萍 Wang Lian;Xie Na;Zhao Peiling;Chen Hao;Li Duyou;Wang Yuping(Clinical Laboratory Center,Affiliated Hospital of Guizhou Medical University,Guiyang 550003,Guizhou Province,China;Department of Clinical Microbiology and Immunology,School of Clinical Laboratory Science,Guizhou Medical University,Guiyang 550004,Guizhou Province,China)

机构地区：[1]贵州医科大学附属医院临床检验中心,贵州省贵阳市550003 [2]贵州医科大学医学检验学院临床微生物学及免疫学教研室,贵州省贵阳市550004

出　　处：《中国组织工程研究》2025年第23期4965-4974,共10页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81860118),项目负责人:王豫萍;贵州省卫健委科学技术基金项目(gzwkj2021-119),项目负责人:王豫萍。

摘　　要：背景:大麻二酚具有抗炎、抗氧化等药理学作用,并且不具有精神活性,在肝脏疾病中的研究日渐增加,但其对肝星状细胞转化生长因子β1/Smad信号转导通路的作用尚未明确。目的:探讨大麻二酚对肝星状细胞中转化生长因子β1/Smad信号转导通路的影响,研究其抗肝纤维化的可能机制。方法:(1)体外实验:选取大鼠肝星状细胞株(HSC-T6),分6组培养:对照组常规培养24 h,单纯药物组加入大麻二酚培养24 h,造模组加入转化生长因子β1培养24 h,造模+低剂量药物组、造模+高剂量药物组、造模+阳性对照组均加入转化生长因子β1培养24 h后分别加入1,5μmol/L大麻二酚或水飞蓟素培养24 h。培养结束后,检测各组细胞α-平滑肌肌动蛋白与Ⅰ型胶原mRNA表达、白细胞介素1β与肿瘤坏死因子α水平及Ⅰ型胶原、转化生长因子β1/Smad信号转导通路蛋白表达。(2)动物体内实验:将C57BL/6J小鼠随机分为5组,每组8只:假手术组不造模,造模组、造模+低剂量药物组、造模+高剂量药物组、造模+阳性对照组通过胆管结扎法建立肝纤维化模型,造模3周后分别腹腔注射4,8 mg/kg大麻二酚或水飞蓟素,1次/d,连续给药7 d。给药结束后,检测各组小鼠肝功能、肝脏病理形态及α-平滑肌肌动蛋白、Ⅰ型胶原、转化生长因子β1/Smad信号转导通路相关蛋白表达。结果与结论:(1)体外实验:与对照组比较,造模组HSC-T6细胞α-平滑肌肌动蛋白与Ⅰ型胶原mRNA表达、白细胞介素1β与肿瘤坏死因子α水平以及Ⅰ型胶原、转化生长因子β1、p-Smad2/3蛋白表达均升高(P<0.05),Smad7蛋白表达降低(P<0.05);两种剂量大麻二酚处理可改善转化生长因子β1诱导的HSC-T6细胞上述指标的变化,并且以造模+高剂量药物组改善作用更明显;(2)体内实验:与假手术组比较,模型组小鼠血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶活性升高(P<0.05),肝组织中炎性细�BACKGROUND:Cannabidiol has anti-inflammatory,antioxidant,and other pharmacological effects,and has no mental activity,so the research in liver disease is increasing day by day,but its effect on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells is not clear.OBJECTIVE:To investigate the effect of cannabidiol on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells and its possible mechanism of anti-hepatic fibrosis.METHODS:(1)In vitro experiment:Rat hepatic stellate cell line(HSC-T6)was selected and cultured in six groups.The control group was routinely cultured for 24 hours.The simple drug group was cultured with cannabidiol for 24 hours.The modeling group was cultured with transforming growth factorβ1 for 24 hours.The modeling+low-dose drug group,the modeling+high-dose drug group,and the modeling+positive control group were cultured with transforming growth factorβ1 for 24 hours,1,5μmol/L cannabidiol and silymarin were cultured for 24 hours.After culture,the mRNA expression ofα-smooth muscle actin and type I collagen,the levels of interleukin 1βand tumor necrosis factorα,and the protein expression of type I collagen and transforming growth factorβ1/Smad signal transduction pathway were detected in each group.(2)In vivo experiments:C57BL/6J mice were randomly divided into five groups with eight mice in each group.Models were not established in the sham operation group.The liver fibrosis models were established by biliary ligation in the modeling group,the modeling+low-dose drug group,the modeling+high-dose drug group,and the modeling+positive control group.At 3 weeks after the modeling,4,8 mg/kg cannabidiol or silymarin were injected intraperitoneally,once a day,for 7 consecutive days.After administration,the liver function,liver pathological morphology,expression levels ofα-smooth muscle actin,type I collagen,and transforming growth factorβ1/Smad signal transduction pathway related protein were detected in each group.RESULTS AND

关 键 词：大麻二酚 肝星状细胞 肝纤维化 信号转导通路 转化生长因子Β1/SMAD HSC-T6细胞 

分 类 号：R453.9[医药卫生—治疗学] R313[医药卫生—临床医学] R575