加味温胆汤对雌性营养性肥胖大鼠LEP,ACC和MCA的影响

目的:通过检测大鼠组织中瘦素(LEP),乙酰辅酶A羧化酶(ACC)和丙二酸单酰辅酶A(MCA)相关蛋白及其基因的表达水平,探讨加味温胆汤有效改善雌性营养性肥胖大鼠脂质代谢紊乱的作用机制和量效关系。方法:将50只SD雌性大鼠按体质量随机分为5组,分别为正常组,模型组,加味温胆汤高、中、低剂量组(18.2,9.1,4.55 g·kg^-1)。除正常组外,其余均采用"普通饲料+高脂乳剂+碳酸饮料"混合饲养法建立营养性肥胖大鼠模型,连续灌胃给药5周,各组动物经末次给药后,麻醉取材。采用酶联免疫吸附测定(ELISA)分别检测各组大鼠血清LEP,肝和腓肠肌组织ACC的含量。采用实时荧光定量聚合酶链式反应(Real-time PCR)检测各组大鼠下丘脑组织LEP,MCA mRNA和肝组织ACC2 mRNA的表达水平。结果:与正常组比较,模型组大鼠体质量、脂肪指数显著增加(P<0.05);与模型组比较,加味温胆汤中剂量组可显著下调下丘脑组织LEP,MCA mRNA的表达水平(P<0.01),加味温胆汤低剂量组显著下调大鼠血清LEP,下丘脑组织LEP,MCA mRNA和肝组织ACC2 mRNA的表达水平(P<0.05,P<0.01);与加味温胆汤高剂量组比较,中剂量组在下调下丘脑LEP,MCA mRNA的表达水平效果最佳,低剂量组次之(P<0.05,P<0.01)。结论:加味温胆汤抗雌性大鼠营养性肥胖的作用机制与干预大鼠LEP抵抗,降低肝组织ACC2 mRNA和下丘脑MCA mRNA的表达水平有关,其中以中、低剂量组效果更佳。

Effect of Modified Wendantang on LEP, ACC and MCA in Female Nutritional Obese Rats

Objective: To detect the expression levels of leptin (LEP), acety-coenzyme A carboxylase(ACC) and malonyl-CoA (MCA)-related proteins and their genes in rat tissues, in order to explore the mechanism and dose-effect relationship of modified Wendantang in alleviating lipid metabolism disorder in female nutritional obese rats. Method: Totally 50 SD female rats were randomly divided into 5 groups according to body weight, namely the normal control group, the model control group, and high, medium and low-dose modified Wendantang groups (18.2, 9.1, 4.55 g·kg^-1). Except the normal control group, the remaining rats were fed with "common feed + high fat emulsion + carbonated beverage" to establish the model of nutritional obesity, and then continuously given drugs by gavage for 5 weeks. After the last drug administration to animals in each group, the rats were anaesthetized to collect materials. The serum LEP, and liver and gastrocnemius ACC levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) was used to detect the expressions of LEP, MCA and ACC2 mRNA in the hypothalamus and liver tissues of each group. Result: Compared with the normal control group, the body weight and fat index of the model control group increased significantly (P<0.05). Compared with the model control group, the medium-dose modified Wendantang group could significantly down-regulate the expressions of LEP, MCA mRNA in rat hypothalamus (P<0.01). The low-dose group can significantly down-regulate the expression levels of serum LEP, hypothalamus tissue LEP, MCA mRNA and liver tissue ACC2 mRNA (P<0.05, P<0.01). Compared with the high-dose modified Wendantang group and the middle-dose modified Wendantang group had the best effect in down-regulating the expressions of LEP and MCA mRNA in the hypothalamus of rats, which were followed by the low-dose group (P<0.05, P<0.01). Conclusion: The mechanism of modified Wendantang against nutritional obesity in female rats is related to the intervention of LEP resistance and the decrease of the expression level of ACC2 mRNA in liver tissue and MCA mRNA in hypothalamus tissue. The middle and low-dose groups have a better effect.