首页|镰形棘豆总黄酮对CC14诱导的肝纤维化大鼠的作用机制研究

镰形棘豆总黄酮对CC14诱导的肝纤维化大鼠的作用机制研究

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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%CC14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)、(5 885.42±948.37)、(4 454.60±489.27)、(4 650.47±843.53)、(3 761.75±887.30)和(3 544.90±1 066.75)μg·L-1,谷草转氨酶水平分别为(186.90±46.89)、(5 936.23±793.81)、(3 971.37±780.28)、(4 360.30±863.35)、(3 943.10±439.47)和(3 971.38±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-a 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-βl mRNA 相对表达水平分别为1.00±0.00、60.99±15.70、9.61±1.59、7.37±1.09、6.41±0.64 和6.87±1.09,Smad7 mRNA 相对表达水平分别为 1.00±0.00、0.34±0.05、0.21±0.03、0.35±0.02、0.38±0.02和0.42±0.03.模型组的上述指标与正常组比较,中、高剂量实验组的上述指标与模型组比较,在统计学上差异均有统计学意义(P<0.05,P<0.01,P<0.001).结论 镰形棘豆总黄酮对CC,4诱导的大鼠肝纤维化具有保护作用,其机制可能与调节TGF-β/Smad通路有关.
Effects of total flavonoids of Oxytropis falcata Bunge on CCl4-induced liver fibrosis in rats
Objective 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%CC14 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),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±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;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Oxytropis falcata Bungetotal flavonoidscarbon tetrachlorideliver fibrosis ratstransforming growth factor-β/Smad pathway

杨天艳、马新换、徐志伟、李荣焜、马芳兄、何宝峰、陈亮、陈晓晴、张君

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甘肃中医药大学药学院,甘肃兰州 730000

甘肃省第二人民医院院长办公室,甘肃兰州 730099

甘肃省中医院科研制剂中心,甘肃兰州 730050

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

兰州市科技局基金资助项目

2022-3-7

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(14)
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