姜黄素和水飞蓟素对大鼠非酒精性脂肪性肝炎的作用及机制比较

Curcumin and silymarin for nonalcoholic steatohepatitis in rats: Comparison of effects and mechanisms

目的:研究并探讨姜黄素和水飞蓟素对干预非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)的不同作用机制.方法:通过高脂饮食诱导大鼠制备NASH模型.将48只健康♂SD大鼠平均分成4组,其中正常组12只,给予普通正常饲料;模型组12只,姜黄素组12只,水飞蓟素组12只,均给予高脂饲料,即碳水化合物∶脂肪∶蛋白质为37∶45∶18.NASH模型制备成功后,姜黄素组每天还需按时给予治疗量的姜黄素羧甲基纤维素(carboxy methyl cellulose,CMC)混悬液50 mg/k g,水飞蓟素组每天按时给予水飞蓟素CMC混悬液100 mg/kg,正常组和模型组给予CMC溶液灌胃.治疗时间为6 wk.对比大鼠肝脏、血清生物化学指标、胰岛素抵抗水平、组织病理学、组织谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)、放射免疫和过氧化物酶体增殖物激活受体α(peroxisome proliferators-activated receptorα,PPARα)m RNA表达.结果:模型组大鼠的肝指数、总胆固醇(total cholesterol,TC)、谷草转氨酶(aspartate amino transferase,AST)、谷丙转氨酶(alanine transaminase,ALT)、血清三酰甘油、MDA、空腹胰岛素(fasting insulin,FINS)、空腹血糖(fasting plasma glucose,FPG)和肿瘤坏死因子α(tumor necrosis factorα,TNF-α)显著高于正常组和两个治疗组;水飞蓟素组PPARαm RNA表达明显高于模型组和姜黄素组,FINS和FPG的含量显著低于姜黄素组.结论:姜黄素、水飞蓟素对高脂饮食诱导制备大鼠NASH模型具有一定的干预作用,但二者的作用机制不同,姜黄素是通过抗炎和抗氧化作用作用于NASH,水飞蓟素则是通过促进肝脏PPARαm RNA的表达抑制NASH的发生和发展.

AIM： To investigate the effects of curcumin and silymarin on nonalcoholic steatohepatitis（NASH） in rats and the underlying mechanisms.METHODS： Forty-eight SD rats were randomly divided into four groups： a normal control group, a model group, a curcumin group and a silymarin group. NASH was induced by feeding a fat-rich diet in all rats except the normal control group. The rats in the curcumingroup and silymarin group were treated with curcumin and silymarin, respectively. After six weeks, all the rats were sacrificed. Serum alanine aminotransferase（ALT）, triglyceride（TG）, total cholesterol（TC）, malondialdehyde（MDA）, superoxide dismutase（SOD） and hepatic TG, TC, MDA, and SOD were measured. Expression of peroxisome proliferator activated receptor α（PPARα） m RNA in the liver was detected. RESULTS： Compared with the other three groups, serum ALT, TG, TC, MDA and hepatic TG, TC, and MDA in the model group were significantly higher. The expression of PPARαm RNA in the liver of rats in the silymarin group was significantly higher than that in the curcumin group, while serum fasting insulin（FINS） and fasting plasma glucose（FPG） were significantly lower. CONCLUSION： Both curcumin and silymarin are effective in treating rat nonalcoholic fat liver, but the mechanisms are different. Curcumin exerts anti-inflammatory and antioxidant effects, and silymarin promotes hepatic PPARαm RNA expression.