摘要
目的:探讨大黄酸和吡格列酮各自对高脂诱建的大鼠非酒精性脂肪性肝炎(NASH)的影响及其可能的机制。方法:52只清洁级雄性SD大鼠,体重140～160 g,随机分成4组:对照组(n=14)、模型组(n=14)、大黄酸组(n=12)、吡格列酮组(n=12)。模型组由高脂高胆固醇饲料(普通饲料+10%猪油+2%胆固醇配制)喂养,药物组均在12周高脂饮食后即造模成功后给予干预。大黄酸用生理盐水配成5 g/L混悬液,每天固定时间100 mg.kg-1.d-1灌胃,吡格列酮组8 mg.kg-1.d-1灌胃。于第20周处死。测定所有动物体重、肝湿重、计算肝指数;测定空腹血糖(FBG)、转氨酶及血脂水平;放射免疫法测空腹胰岛素(FINS)及TNFα-,计算胰岛素抵抗指数;酶法测定肝组织匀浆丙二醛(MDA)、谷胱甘肽过氧物酶(GSH-Px)水平;HE染色肝病理组织切片。结果:与模型组相比,药物组ALT、AST、血糖、胰岛素及胰岛素抵抗指数、TNFα-、MDA有明显下降;大黄酸组肝脂肪变较吡格列酮组明显(P<0.05),但其肝内炎症较吡格列酮组轻。结论:大黄酸和吡格列酮对大鼠NASH均有治疗作用,但在改善肝脂肪变及炎症方面有所不同。
AIM： To approach the therapeutic effect of rhein and pioglitazone respectively on nonalcoholic steatosis hepatitis （NASH）rats and the possible mechanism. METHODS： 52 male SD rats were randomly divided into 4 groups： control group （ n = 14）, model group （ n = 14）, rhein group （ n = 12）, pioglitazone group （ n = 12）, the body weight were 140 - 160 g. Control group were fed with normal diet for 20 weeks （2 rats for 12 weeks and then were executed）. Model group were fed with high-fat and high-cholesterol diet consisting of normal diet, 10% lard and 2% chol- esterol, for 20 weeks （2 rats for 12 weeks and then were executed）. Drugs were given after 12 weeks fed with high-fat and high-cholesterol diet. Rhein （5 g/L suspension） was prepared with normal saline, intragastric administration（ 100 mg· kg^- 1 · d^- 1 ） everyday in fixation time. Pioglitazone group （ 8 mg· kg^-1· d^- 1） were intragastrie administered. All rats were executed after 20 weeks, and the body weight, liver humid weight were determined, the liver index number was calculated. The levels of fasting blood glucose （FBG）, aminopherase and blood fat were determined. The fasting insulin （FINS） and TNF-α were measured by radio-immunoassay, the insulin resistance index was caleulat-ed. The levels of malonaldehyde （MDA）, glutathione peroxidase（GSH-Px） in hepatic tissue bomogenate were measured using enzymic method, the liver histopathologic slides were dyed with HE dyeing. RESULTS： Compared with model group, the levels of ALT, AST, blood glucose, insuline, insulin resistance index, TNF- α, MDA were obviously decreased in drug groups. Compared with pioglitazone group, the hepatic steatosis in rhein was obvious （ P 〈 0.05）, but the inflammation in liver was lower grade. CONCLUSION： Rehin and pioglitazone have therapeutical effects on NASH rats. However, they are different in the aspects of improving hepatocyte steatosis and inflammatory.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2009年第4期397-401,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
浙江省医药卫生科学研究基金计划(2007B208)
瑞安市科技计划项目基金资助(20072162)
关键词
非酒精性脂肪性肝炎
大黄酸
吡格列酮
胰岛素抵抗
脂质代谢紊乱
nonalcoholic steatosis hepatitis
rhein
pioglitazone
insulin resistance
fatty substance metabolic disorder
