茯苓多糖改善HDL功能并通过PPARγ/LXRα/ABCA1抗AS机制研究

Study on anti-AS mechanism of pachyman by improving HDL function and mediating PPARγ/LXRα/ABCA1

目的:探讨茯苓多糖改善HDL功能以及通过PPARγ/LXRα/ABCA1信号通路防治AS的作用及机制研究。方法:将32只ApoE-/-小鼠随机分为模型组、茯苓多糖组、辛伐他汀组,10只C57BL/6J作为正常组。模型组及药物干预组给予高脂饲料喂养,正常组给予普通饲料喂养。8周后,药物干预组每日灌胃相应药物,茯苓多糖组以0.2 g/(kg·d)灌胃,辛伐他汀组以2.275 mg/(kg·d)灌胃,正常组与模型组给予等量生理盐水。12周后,全自动生化仪检测血清三酰甘油(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)的含量;HE及油红O染色法观察肝脏脂质沉积情况;ELISA法检测血清SAA、S1P含量;Real-time RT-PCR法及Western blot法检测肝脏PPARγ、LXRα、ABCA1、CYP7A1、SR-B1 mRNA及蛋白表达。结果:与正常组比较,模型组小鼠血清TC、TG、LDL-C水平明显升高,HDL-C水平明显降低(P<0.05),肝脏可见脂质沉积,血清S1P含量、肝脏PPARγ、LXRα、ABCA1、CYP7A1、SR-B1 mRNA及蛋白表达显著降低,血清SAA含量显著升高(P<0.05);与模型组比较,茯苓多糖组、辛伐他汀组血清中TC、TG、LDL-C显著降低,HDL-C显著升高(P<0.05),肝脏脂质沉积面积减少,血清S1P含量,肝脏PPARγ、LXRα、ABCA1、CYP7A1、SR-B1 mRNA及蛋白表达显著升高,血清SAA含量显著降低(P<0.05)。结论:茯苓多糖能够改善HDL功能,同时可通过胆固醇逆转运PPARγ/LXRα/ABCA1信号通路防治AS。

Objective:To explore the effect and mechanism of pachyman on the prevention and treatment of AS by improving HDL function and mediating PPARγ/LXRα/ABCA1 signal pathway.Methods:32 ApoE-/-mice were randomly divided into model group,pachyman group and simvastatin group.10 C57 BL/6 J mice were used as normal group.The model and drug intervention group were fed with high-fat diet,and the normal group were fed with normal diet.After 8 weeks,the drug intervention group was given corresponding drugs every day,the pachyman group was perfused with 0.2 g/(kg·d),and the simvastatin group was perfused with2.275 mg/(kg·d).The normal group and the model group were given the same amount of normal saline.After 12 weeks,the contents of serum triglyceride(TG),cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)were measured by automatic biochemical analyzer,the lipid deposition of liver was observed by HE and oil red O staining,the contents of serum SAA and S1 P were detected by ELISA,and the expressions of PPARγ,LXRα,ABCA1,CYP7 A1,SR-B1 mRNA and protein in liver were detected by Real-time RT-PCR and Western blot.Results:Compared with the normal group,the level of serum TC,TG,LDL-C in the model group increased significantly,the level of HDL-C decreased significantly(P<0.05),the lipid deposition could be seen in the liver,the content of S1 P in serum,the expression of PPARγ,LXRα,ABCA1,CYP7 A1,SR-B1 mRNA and protein in liver decreased significantly,and the content of SAA in serum increased significantly(P<0.05).Compared with the model group,serum TC,TG,LDL-C in pachyman group and simvastatin group significantly decreased,HDL-C significantly increased(P<0.05),liver lipid deposition area decreased,serum S1 P content,liver PPARγ,LXRα,ABCA1,CYP7 A1,SR-B1 mRNA and protein expression significantly increased,serum SAA content significantly decreased(P<0.05).Conclusion:Pachyman can prevent and treat AS by improving HDL function and mediating cholesterol reverse transport PPARγ/LXRα/ABCA1 signal pathway.