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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
【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.
【Key words】 emodin(大黄素); hepatic fibrosis; Smad7; α-SMA; masson trichrome staining;
- 【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