摘要
目的:探讨芍药苷对非酒精性脂肪肝大鼠的疗效及保护机制。方法:健康雄性SD大鼠62只,随机分为正常对照组(11只)和模型组(51只),模型组给予高脂饲料喂养10周后,分别从正常组和模型组随机挑选1只,取肝脏做病理切片,证实非酒精性脂肪肝形成。造模成功后将模型组随机分为5组:空白模型组、芍药苷高、中、低剂量组、双环醇组,每组10只。正常组与模型组予以0.9%氯化钠溶液灌胃,5mL/次,芍药苷治疗组分别以200、100、50mg·kg-1·d-1芍药苷混悬液灌胃,双环醇组以100mg·kg-1·d-1双环醇混悬液灌胃。持续4周后处死动物,测量各组大鼠的体质量及肾周和附睾脂肪,分离血清,检测、计算各组大鼠血糖、胰岛素等指数及血清脂联素水平。HE染色观察肝脏病理学改变,油红O染色观察肝细胞内脂质沉积状况,RT-PCR法评价肝脏腺苷酸活化蛋白激酶(AMPK)磷酸化水平、脂肪酸合成酶(FAS)和固醇调控元件结合蛋白(SREBP-1c)的mRNA基因表达。结果:第14周后,与正常组相比,模型组大鼠表现出内脏型肥胖,胰岛素敏感性及血清(APN)水平、肝组织内AMPK磷酸化水平均显著下降(P<0.05,P<0.01);同时脂质合成基因SREBP-1c和FAS的mRNA表达量显著增多。与模型组比较,芍药苷高、中、低剂量组、双环醇组可改善胰岛素抵抗(P<0.05,P<0.01),上调血清APN水平(P<0.05,P<0.01),减轻各治疗组大鼠内脏型肥胖(P<0.05,P<0.01),提高肝组织内AMPK磷酸化水平及抑制脂质合成基因SREBP-1c和FAS的mRNA表达量。结论:芍药苷可以提高肝脏内AMPK活性,并可以改善高脂饮食导致的大鼠IR,减少肝脏细胞内脂质堆积,从而改善非酒精性脂肪肝,其机制可能与激活AMPK和抑制肝细胞脂质合成途径有关。
Objective： To discuss the effect of Paeoniflorin on insulin resistance rats induced by high fat diet and explore the mechanism of its protection. Methods： 62 healthy male rats were randomly divided into control group （NC group） （n=l 1） and high-fat group （n=51）, respectively fed with normal chow and high fat diet. The high-fat group was divided into five groups： the PE200-treated group （n=10）, the PE100-treated group （n=10）, the PE50-treated group （n=10）, the Bicyclol-treated group （n=10）, and the model group （n=10）. After ten weeks, the animals in the PE200-treated group, the PE100-treated group and the PE50- treated group were orally administered paeonia abra （PE） （200, 100 and 50mg·kg^-1·d^-1） for 4 weeks. The animals in the Bicyclol- treated group were orally administered Bicyclol （100mg·kg^-1·d^-1） for four weeks, and the model group was treated with distilled water. Rats in each group were kept for 14 weeks before killed. Adipose tissue around kidney and epididymis were dissected. And the FBG, FINS, IRI, ISI were measured. The weight of adipose tissue and body were measured. And serum adiponectin （APN） level was detected by ELISA. Liver histology was detected by HE Staining and Oil-red O staining. The gene expressions of Phosphorylation of AMP-activated kinase （AMPK）, and two key lipogenesis regulators of SREBP-1 c and FAS were detected by RT-PCR. Results： Insulin resistance rats were induced by high-fat diet for 10 weeks successfully. After 14 weeks feeding, the rats in model group showed obvious visceral obesity. Compared with NC group, adipocyte size significantly increased in model group （P〈0.05, P〈0.01）. However, insulin sensitivity and serum APN level in model group were much lower than those of NC group （P〈0.01）. Compared with model group, the insulin sensitivity as well as serum APN level of rats in the four treated groups had obviously improved （P〈0.05, P〈0.01）. Phosphorylation of AMPK levels in model group decreased with the regulation of SREBP-a and FAS gene high expressions （P〈0.05, P〈0.01）, but phosphorylation of AMPK levels increased and the expressions of SREBP-a and FAS gene decreased by peony extract treatment for four weeks （P〈0.05, P〈0.01）. Conclusion： Peony extract administration significantly improved insulin resistance induced by high fat diet, and the mechanism might be related to the improvement of the visceral obesity and up-regulation of the serum APN level.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2013年第5期1376-1381,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
北京市中医科技重点规划项目(No.KJTS2011_01)
北京市卫生系统高层次卫生技术人才培养计划(No.2011-2-13)~~
关键词
非酒精性脂肪肝
芍药苷
胰岛素抵抗
脂质代谢异常
Nonalcobolic fatty liver disease
Paeonia abra
Insulin resistance
Lipid metabolism disorder
