三子养亲汤对正常高值血压痰湿壅盛证大鼠PPARα/CPT-1通路的影响

Effect of Sanzi Yangqin Decoction(三子养亲汤)on PPARα/CPT-1 Pathway in Rats with Phlegm-Dampness Obstruction Syndrome of High-Normal Blood Pressure

目的:基于过氧化物酶体增殖物激活受体(PPARα)/肉毒碱棕榈酰基转移酶-1(CPT-1)通路探究三子养亲汤对正常高值血压痰湿壅盛证大鼠脂质代谢的影响。方法:将50只Wistar大鼠随机分成空白组10只及造模组40只,空白组给予维持饲料,造模组采用高脂饲料饲养+高盐(6%盐水)灌胃方式制备正常高值血压痰湿壅盛证大鼠模型,造模8周,模型构建成功后将40只大鼠随机分为模型组及三子养亲汤低、中、高剂量组,每组各10只。其后,空白组给予生理盐水灌胃,造模组继续给予高脂饲料加6%盐水灌胃,同时三子养亲汤各组给予相应浓度水煎液灌胃。灌胃8周后,检测各组大鼠体质量、血压、血脂四项及肝脏生化指标,观察肝脏病理形态及脂质沉积情况,检测大鼠肝脏中PPARα、CPT-1、酰基辅酶A氧化酶(ACOX1)基因和蛋白的表达。结果:与模型组比较,三子养亲汤高剂量组体质量、血压及血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇、丙氨酸转氨酶、天冬氨酸转氨酶均显著下降(P<0.05或P<0.01)。空白组大鼠肝细胞排列整齐,细胞核形态完整,无红色脂质沉积;模型组大鼠肝细胞排列不整齐,出现细胞核消失的现象,肝细胞内出现部分脂质沉积;三子养亲汤高剂量组肝细胞排列规则、细胞核完整,有较少红色脂质沉积;三子养亲汤中、低剂量组细胞核较完整,肝细胞排列较整齐,有少量红色脂质沉积。与模型组比较,三子养亲汤高剂量组PPARα、CPT-1、ACOX1蛋白表达水平明显升高(P<0.05或P<0.01),中剂量组ACOX1蛋白表达水平升高(P<0.05)。与模型组比较,三子养亲汤高剂量组PPARα、CPT-1、ACOX1mRNA水平升高(P<0.05或P<0.01),三子养亲汤低、中剂量组ACOX1mRNA水平升高(P<0.01)。结论:三子养亲汤可改善正常高值血压痰湿壅盛证大鼠体质量、血压、血脂及肝脏生化指标等。其机制可能与三子养亲汤调控PPARα/CPT-1信号通路,促进脂肪酸氧化分解,进而调控肝脏脂质代谢相关。

Objective:To investigate the effect of Sanzi Yangqin Decoction(三子养亲汤)on lipid metabolism in rats with phlegm-dampness obstruction syndrome of high-normal blood pressure based on PPARα/CPT-1 signal pathways.Methods:Total fifty Wistar rats were randomly divided into the blank group of 10 and the modeling group of 40.The blank group was given maintenance diet,and the modeling group was fed with high-fat diet and high salt(6%saline)by gavage for 8 weeks to establish the rat model of phlegm-dampness obstruction syndrome of high-normal blood pressure.After the success of model construction,40 rats were randomly divided into the model group,and low,medium and high dose groups of Sanzi Yangqin Decoction,with 10 rats in each group.The blank group was given saline by gavage,the model group continue to be given high fat feed and 6%saline by gavage,at the same time,the groups of Sanzi Yangqin Decoction were given the corresponding concentration of decoction by gavage.After 8 weeks of gavage,the body weight,blood pressure,blood lipid,liver biochemical indexes,liver pathological morphology and lipid deposition were observed,and the gene and protein expressions of PPARα,CPT-1,and acyl-coa oxidase(ACOX1)in the liver of rats were detected.Results:Compared with the model group,the body weight,blood pressure,and serum triglyceride,total cholesterol,low density lipoprotein-cholesterol,alanine transaminase,aspartate transaminase in the high-dose group of Sanzi Yangqin Decoction had a substantial decrease(P<0.05 or P<0.01).The hepatocytes of rats in the blank group were arranged neatly,with complete nuclei and no red lipid deposition.In the model group,the hepatocytes were not arranged neatly,the nuclei disappeared,and some lipids were deposited in the hepatocytes.The high-dose group of Sanzi Yangqin Decoction had regular arrangement of hepatocytes and complete nuclei,with less red lipid deposition whereas the medium and low dose groups had less complete nuclei and less regular arrangement of hepatocytes,with a small amount of red lipid deposition.Compared with the model group,the protein expression levels of PPARα,CPT-1 and ACOX1 in the high-dose group of Sanzi Yangqin Decoction were increased(P<0.05 or P<0.01),and the protein expression level of ACOX1 in the medium-dose group was increased(P<0.05).Compared with the model group,the protein expression levels of PPARα,CPT-1 and ACOX1 mRNA in the high-dose group of Sanzi Yangqin Decoction were increased(P<0.05 or P<0.01),and the levels of ACOX1 mRNA in the medium and low dose groups were increased(P<0.01).Conclusions:Sanzi Yangqin Decoction can improve the body weight,blood pressure,blood lipids,and liver biochemical indexes in rats with phlegm-dampness obstruction syndrome of high-normal blood pressure.Its mechanism may be related to participate in regulating PPARα/CPT-1 signaling pathway,promote the oxidative decomposition of fatty acids,thereby playing a role in regulating hepatic lipid metabolism.