雌马酚对肥胖模型大鼠脂代谢的影响

EFFECT OF EQUOL ON LIPID METABOLISM IN OBESE RATS

目的 观察雌马酚(equol,Eq)对高脂饮食(high-fatdiet,HFD)联合去卵巢(ovariectomized,OVX)诱导的肥胖模型大鼠脂代谢的影响,并探讨其作用机制。方法 6w龄雌性SD大鼠32只,随机分为:对照组(control)、模型(model,OVX+HFD)组、模型+低剂量Eq干预组[model+LEq,20mg/(kg·d)],模型+高剂量Eq干预组[model+HEq,40mg/(kg·d)],每组8只。每周测量体重,干预12w后麻醉处死大鼠,测量肝脏湿重、体长、腹部脂肪重量,计算肝脏指数、Lee’s指数和脂体比;检测大鼠血清TG、TC、HDL-C、LDL-C、ALT、AST、TNFα、IL-6、空腹胰岛素(fasting insulin,FINS)、空腹血糖(fasting plasma glucose,FPG)及肝脏TG、TC水平,计算稳态模型的胰岛素抵抗指数(homeostasis model assessment-IR,HOMA-IR);肝脏组织HE、油红O染色,Western bloting检测肝脏和脂肪组织过氧化物酶体增殖活化受体γ(peroxisome proliferator-activated receptor-gamma,PPARγ)蛋白表达。结果 Eq干预能降低模型大鼠体重、腹部脂肪重量、肝脏指数、Lee’s指数和脂体比,减轻HOMA-IR水平(P<0.05);增加血清HDL-C水平,降低血清TG、TC、LDL-C、ALT、AST、TNFα、IL-6及肝脏TG、TC水平(P<0.05);减轻肝组织脂质积累和脂肪变性;降低肝脏PPARγ表达水平,升高脂肪组织PPARγ表达水平(P<0.05)。结论 Eq能有效改善HFD联合OVX诱导的大鼠肥胖合并肝脂肪变性,其部分机制可能与Eq调控PPARγ表达、改善胰岛素敏感性和减轻炎症反应有关。

Objective To observe the effect of equol(Eq)on lipid metabolism in obese rats induced by high-fat diet(HFD)combined with ovariectomized(OVX)and explore its mechanism of action.Methods Thirty-two 6-week-old female SD rats were randomly divided into 4 groups:control group,model(OVX+HFD)group,model+low dose Eq group(LEq,20mg/(kg·d)),high dose Eq group(HEq,40 mg/(kg d)).The rats were weighed weekly.After 12 weeks of intervention,rats were sacrificed for sampling in anesthetized condition.Liver wet weight,body length,and abdominal fat weight were measured and the liver index,Lee's index and fat body ratio were calculated.Serum levels of TG,TC,HDL-C,LDL-C,ALT,AST,TNFa,IL-6,fasting insulin(FINS),fasting blood glucose(FPG)and liver TG,TC contents were detected and homeostasis model assessment-IR(HOMA-IR)was calculated.Liver tissue was stained with HE and Oil Red O.The expression of peroxisome proliferator-activated receptor-gamma(PPARy)protein in the liver and adipose tissue was detected by Western blotting.Results Eq intervention could reduce body weight,abdominal fat weight,liver index,Lee's index,fat body ratio and alleviate HOMA-IR level(P<0.05).Eq intervention increased serum HDL-C level and reduced serum TG,TC,LDL-C,ALT,AST,TNF a,IL-6 and liver TG,TC levels(P<0.05).Eq intervention could reduce lipid accumulation and decrease the expression level of PPAR in the liver and increase the expression level of PPAR in adipose tissue(P<0.05).Conclusion Eq is effective in ameliorating obesity complicated with hepatic steatosis in rats induced by HFD combined with OVX,and this action is related to the regulation of PPARy expression,improvement of insulin sensitivity and reduction of inflammatory response by Eq.