通络软肝方对肝纤维化大鼠TGF-β1/Smad信号通路和氧化应激的影响  

Effects of Tongluo Rugan Prescription (通络软肝方) on TGF-β1/ Smad Signaling Pathway and Oxidative Stress in Rats with Hepatic Fibrosis

作　　者：成琳 刘汶[2] 王雅欣 刘思彤 CHENG Lin;LIU Wen;WANG Yaxin;LIU Sitong(School of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China)

机构地区：[1]北京中医药大学中医学院,北京100029 [2]首都医科大学附属北京中医医院,北京100010

出　　处：《中医药导报》2023年第7期13-18,23,共7页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：北京市大学学生创新创业训练项目(S202110026001);危北海全国名中医传承工作室。

摘　　要：目的:探究通络软肝方对肝纤维化大鼠TGF-β1/Smad信号通路和氧化应激的影响。方法:54只雄性SD大鼠按随机数字表法分为对照组、模型组、阳性药组、通络软肝方低剂量组、通络软肝方中剂量组、通络软肝方高剂量组。除对照组外,其余组大鼠腹腔注射50%CCl4橄榄油溶液,每周2次,连续8周,建立肝纤维化大鼠模型。各给药组大鼠灌胃给予相应药物,对照组和模型组大鼠灌胃给予生理盐水,1次/d,连续6周。检测大鼠血清ALT、AST水平;HE和Masson染色后镜下观察大鼠肝组织病理学变化;Western blotting法检测大鼠肝组织中α-SMA、TGF-β1、Smad3、Smad7蛋白相对表达量;ELISA法检测肝组织SOD、MDA的水平。结果:与对照组比较,模型组大鼠肝组织内可见大量肝细胞变性坏死,炎症细胞浸润和纤维结缔组织增生,胶原面积分数明显升高(P<0.01),血清ALT、AST水平明显升高(P<0.01),肝组织α-SMA、TGF-β1、Smad3蛋白相对表达量及MDA水平均明显升高(P<0.01),Smad7蛋白相对表达量及SOD水平均明显降低(P<0.01);与模型组比较,通络软肝方低、中、高剂量组大鼠肝组织炎症、纤维结缔组织增生明显减轻,肝组织胶原面积分数明显降低(P<0.01),血清中ALT、AST水平均明显降低(P<0.05或P<0.01),肝组织α-SMA、TGF-β1、Smad3蛋白相对表达量及MDA水平均明显降低(P<0.05或P<0.01),Smad7蛋白相对表达量及SOD水平均明显升高(P<0.05或P<0.01)。结论:通络软肝方可以抑制肝纤维化大鼠TGF-β1/Smad信号通路和氧化应激,降低肝组织胶原纤维沉积,保护肝脏功能,发挥抗肝纤维化的作用。Objective:To explore the effect of Tongluo Ruangan Prescription on TGF-β1/Smad signaling pathway and oxidative stress in rats with hepatic fibrosis.Methods:A total of 54 male SD rats were randomly divided into control group,model group,positive drug group,Tongluo Ruangan Prescription low-dose group,Tongluo Ruangan Prescription medium-dose group and Tongluo Ruangan Prescription high-dose group.Except for the control group,the rats in the other groups were intraperitoneally injected with 50%CCl4 olive oil solution twice a week for 8 weeks to establish a rat model of hepatic fibrosis.Rats in each treatment group were given corresponding drugs by gavage,while rats in the control group and model group were given physiological saline by gavage once a day for 6 consecutive weeks.The levels of serum ALT and AST in serum of rats were detected by the test kit.The pathological changes of liver tissue in rats were observed under microscope after HE and Masson staining.The relative protein expression levels ofα-SMA,TGF-β1,Smad3 and Smad7 in rat liver tissue were detected by Western blotting.The levels of SOD and MDA in liver tissue were detected by ELISA.Results:Compared with the control group,a large number of hepatocyte degeneration and necrosis,inflammatory cell infiltration and fibrous connective tissue hyperplasia were observed in the liver tissue of the model group.The collagen area fraction was significantly increased(P<0.01),and the serum ALT and AST levels were significantly increased(P<0.01).The relative expression ofα-SMA,TGF-β1,Smad3 protein and MDA level in liver tissue were significantly increased(P<0.01),and the relative expression of Smad7 protein and SOD level were significantly decreased(P<0.01).Compared with the model group,the liver tissue inflammation and fibrous connective tissue hyperplasia of rats in Tongluo Ruangan Prescription low,medium and high-dose groups were significantly reduced,the collagen area fraction of liver tissue was significantly decreased(P<0.01).The levels of ALT and AST in seru

关 键 词：肝纤维化 通络软肝方 TGF-Β1/SMAD信号通路 氧化应激 大鼠 

分 类 号：R285.5[医药卫生—中药学]