镰形棘豆总黄酮对CCl_(4)诱导的肝纤维化大鼠的作用机制研究  

Effects of total flavonoids of Oxytropis falcata Bunge on CCl_(4)-induced liver fibrosis in rats

作　　者：杨天艳 马新换 徐志伟[3] 李荣焜 马芳兄 何宝峰 陈亮 陈晓晴 张君 YANG Tian-yan;MA Xin-huan;XU Zhi-wei;LI Rong-kun;MA Fang-xiong;HE Bao-feng;CHEN Liang;CHEN Xiao-qing;ZHANG Jun(College of Pharmacy,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,Gansu Province,China;Deanery The Second People's Hospital of Gansu Province,Lanzhou 730099,Gansu Province,China;Research Preparation Center,Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,CGansu Province,China)

机构地区：[1]甘肃中医药大学药学院,甘肃兰州730000 [2]甘肃省第二人民医院院长办公室,甘肃兰州730099 [3]甘肃省中医院科研制剂中心,甘肃兰州730050

出　　处：《中国临床药理学杂志》2024年第14期2073-2077,共5页The Chinese Journal of Clinical Pharmacology

基　　金：兰州市科技局基金资助项目(2022-3-7)。

摘　　要：目的探讨镰形棘豆总黄酮对四氯化碳诱发的肝纤维化(HF)大鼠的作用,以及对肝转化生长因子(TGF)-β/Smad信号通路的影响。方法将48只雄性大鼠随机分为正常组(腹腔注射花生油,灌胃给予0.9%NaCl)、模型组(腹腔注射40%CCl4花生油溶液诱导HF模型+灌胃给予0.9%NaCl)、阳性对照组(HF模型+灌胃秋水仙碱0.2 mg·kg^(-1))和低、中、高剂量实验组(HF模型+分别灌胃镰形棘豆总黄酮提取物100、200、400 mg·kg^(-1)),每组8只,连续4周。用苏木精-伊红(HE)、Masson染色方法观察组织病理变化;检测血清肝功能、肝纤维化水平;检测血清炎症因子水平,用荧光定量聚合酶链反应(RT-qPCR)法测定肝中基因的表达水平。结果模型组大鼠肝组织病理损伤严重,大量炎症因子和胶原纤维堆积,而其余给药组均有不同程度缓解。正常组、模型组、阳性对照组和低、中、高剂量实验组的谷丙转氨酶水平分别为(49.28±12.44)、(5885.42±948.37)、(4454.60±489.27)、(4650.47±843.53)、(3761.75±887.30)和(3544.90±1066.75)μg·L^(-1),谷草转氨酶水平分别为(186.90±46.89)、(5936.23±793.81)、(3971.37±780.28)、(4360.30±863.35)、(3943.10±439.47)和(3971.38±631.08)μg·L^(-1),透明质酸水平分别为(45.08±17.16)、(104.32±36.06)、(66.83±20.09)、(70.30±21.07)、(60.00±9.68)和(59.02±10.73)μg·L^(-1),层粘连蛋白水平分别为(23.13±3.89)、(60.85±13.66)、(35.67±9.92)、(39.98±9.39)、(36.55±12.21)和(34.68±24.83)μg·L^(-1),Ⅲ型前胶原水平分别为(24.98±5.34)、(82.58±30.14)、(40.70±16.14)、(51.08±23.21)、(43.60±12.48)、(44.20±11.66)μg·L^(-1),白细胞介素(IL)-1β水平分别为(37.63±1.24)、(46.10±3.23)、(39.22±2.36)、(41.33±0.93)、(40.25±2.04)和(39.18±2.23)pg·mL^(-1),肿瘤坏死因子-α水平分别为(314.58±20.56)、(383.71±16.97)、(349.00±7.93)、(348.88±25.11)、(325.75±27.84)和(335.07±21.33)pg·mL^(-1),TGF-β1 mRNA相对表达水平分别为1.00±0.00、60.99±1Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9%NaCl),model group(intraperitoneal injection of 40% CCl_(4) peanut oil solution induced HF model,intragastric administration of 0.9%NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg^(-1)of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg^(-1)of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5885.42±948.37),(4454.60±489.27),(4650.47±843.53),(3761.75±887.30)and(3544.90±1066.75)μg·L^(-1);glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5936.23±793.81),(3971.37±780.28),(4360.30±863.35),(3943.10±439.47)and(3971.38±631.08)μg·L^(-1);hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L^(-1);laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L^(-1);typeⅢprocollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.6

关 键 词：镰形棘豆 总黄酮 四氯化碳 肝纤维化大鼠 转化生长因子-β/Smad通路 

分 类 号：R28[医药卫生—中药学]