姜黄素与吡格列酮对大鼠非酒精性脂肪性肝炎作用的对照研究

Control study of the effects of curcumin and pioglitazone in nonalcoholic steatohepatitis in rats

目的比较姜黄素和吡格列酮对高脂饮食诱导的大鼠非酒精性脂肪性肝炎(NASH)的作用并探讨其机制。方法 48只SD大鼠随机分为正常组、模型组、姜黄素组和吡格列酮组(每组各12只)。正常组全程饲以普通饲料,另外三组均给予高脂饮食。6周末,每组各处死2只大鼠。验证非酒精性脂肪肝病造模成功后,姜黄素组和吡格列酮组每日分别给予姜黄素50 mg/kg和吡格列酮10 mg/kg灌胃,正常组、模型组给予相应体积的0.5%的羧甲基纤维素钠灌胃。6周治疗结束后,留取血样和肝组织。统计体/肝质量,计算肝指数和胰岛素抵抗指数(HOMA-IR);进行肝功能检测及病理组织学检查;并检测血清FFA、TNF-α和IL-6水平及肝组织FFA、TNF-α、IL-6、MDA、GSH含量和SOD的活性。结果与模型组相比,姜黄素组和吡格列酮组大鼠NAS评分及血清ALT、AST水平均降低(P均<0.05)。模型组较正常组大鼠血清HOMA-IR、FFA、TNF-α、IL-6水平及肝组织TNF-α、IL-6、MDA含量均明显升高(P均<0.01),而姜黄素组、吡格列酮组与模型组大鼠相比,上述指标均降低(P均<0.05),且以姜黄素组大鼠体质量、血清AST、NAS积分及肝组织FFA、MDA下降最为显著(P均<0.01)。结论姜黄素与吡格列酮均可通过调脂、改善IR、抗炎及抗氧化作用防治NASH,但前者的作用更强,且不增加大鼠的体质量。

Objective To compare the effects of curcumin and pioglitazone in high-fat diet induced nonalcoholic steatohepatitis （NASH） in rats and explore their mechanisms. Methods Forty-eight rats were randomly divided into normal group, model group, cureumin group and pioglitazone group. Rats in normal group were fed a standard diet while those in other three groups received a high-fat diet. Two rats from each group were executed at the end of the sixth week to detect the pathological changes. Then, rats in curcumin group and pioglitazone group were gavaged with 50 mg/kg of curcumin or 10 mg/kg of pioglitazone daily. Normal group and model group received an equal volume of 0.5% CMC as controls. At the end of the twelfth week, all rats were executed. Blood and liver samples were collected. Body weight and liver weight were recorded and analyzed, the serum biochemical parameters and liver histological examinations were observed. The serum contents of FFA, TNF-α, IL-6 and the contents of FFA, TNF-α, IL-6, MDA, GSH, the activity of SOD in liver were measured by corresponding methods. Results Compared with model group, NAS scores, serum ALT, AST were decreased in eureumin group and pioglitazone group （P 〈 0.05）. The levels of HOMA-IR, FFA, TNF- α, IL-6 in serum and liver contents of TNF-α, IL-6, MDA were significantly higher in model group than those in normal group （P 〈 0.01 ） ; compared with model group, the levels of above indexes in curcumin group and pioglitazone group were decreased （P 〈0.05） , and the body weight, serum AST, NAS scores and liver contents of FFA, MDA in curcu- min group were much lower （P 〈 0. 01 ）. Conclusion Both cureumin and pioglitazone can prevent and treat NASH via reducing lipid, improving IR, antiinflammatory and antioxidant, but cureumin is superior without body weight gain.