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大黄素对大鼠肝纤维化的影响及机理研究

Effects of emodin on hepatic fibrosis in rats and underlying mechanisms

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【作者】 王晓丽张英博李雪岩牛英才綦艳秋朱兰芹董妙先

【Author】 Wang Xiaoli;Zhang Yingbo;Li Xueyan;Niu Yingcai;Dong Miaoxian;Institute of medicine,Qiqihar Medical College;The Hub Laboratory,Qiqihar Medical College;

【机构】 齐齐哈尔医学院医药科学研究所齐齐哈尔医学院中心实验室齐齐哈尔医学院卫生所

【摘要】 目的:观察大黄素对抗CCl4诱导大鼠肝纤维化的作用及对肝脏组织α-SMA和Smad7蛋白表达的影响。方法:SD大鼠50只随机分为空白对照组(n=10)、CCl4组(n=20)和大黄素+CCl4组(n=20),共3组。用CCl4皮下注射制备大鼠肝纤维化模型。大黄素干预12周后处死大鼠。采用Masson染色法观察肝脏组织的胶原纤维改变,Western blot法检测α-SMA和Smad7蛋白表达水平。结果:CCl4用量为2 ml/kg体重,每周2次,共12周。大黄素按20 mg/kg灌胃处理,每天1次,连续12周。Masson染色结果显示,与空白组相比,CCl4组大鼠肝组织胶原纤维显著增加;与CCl4组比较,大黄素+CCl4组胶原纤维显著减少。Western blot结果显示,与空白组相比,CCl4组α-SMA蛋白表达显著上调,而Smad7蛋白表达显著下调;与CCl4组相比,大黄素+CCl4组α-SMA蛋白表达显著下调,而Smad7蛋白表达显著上调。结论:大黄素具有逆转CCl4诱导大鼠肝纤维化的作用。其机制可能通过上调Smad7、下调α-SMA蛋白表达,进而抑制肝星状细胞活化有关。

【Abstract】 Objective: To investigate the inhibitory effect and possible mechanism of emodin on hepatic fibrosis induced by carbon tetrachloride(CCl 4).Method: Studies were conducted in 50 male Sprague-Dawley rats,and they were randomly divided into 3 groups,named as blank controls group(n = 10),CCl 4 group(n = 20),and emodin + CCl 4 group(n = 20).The rat models of experimental hepatic fibrosis were established by injection with CCl 4.The rats treated with CCl 4 received emodin via oral administration at a dosage of 20 mg·kg·d at the same time.Rats were injected olive oil served as control groups.After 12 weeks,the liver histopathology was examined by Masson trichrome staining.Smad7 and α-SMA protein expression in hepatic tissue were detected by Western blot.Result: Compared with the normal group,the fibrotic area was increased in CCl 4 groups(P < 0.05).The fibrotic area in emodin + CCl 4 group was decreased compared with the CCl 4 group(P < 0.05).Compared with the blank controls group,the α-SMA protein expression was up-regulated in CCl 4 groups(P < 0.05).The α-SMA protein expression in emodin + CCl 4 group was down-regulated compared with the CCl 4 group(P < 0.05).The protein expression levels of Smad7 in the CCl 4 group was significantly down-regulated than that in the normal group,and that from CCl 4 + emodin group was significantly up-regulated than in the CCl 4 group(P < 0.05).Conclusion: emodin exert anti-hepatic fibrosis effect in rats via inhibition of HSC activation by up-regulation expression of Smad7 and down-regulated expression of α-SMA in liver tissue.

【基金】 国家自然科学基金项目(81073080);黑龙江省教育厅科学技术研究面上项目(11551551)
  • 【文献出处】 中药药理与临床 ,Pharmacology and Clinics of Chinese Materia Medica , 编辑部邮箱 ,2013年04期
  • 【分类号】R285
  • 【被引频次】24
  • 【下载频次】488
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