降脂通脉饮对高血脂症大鼠血脂和PERK/ATF4/CHOP信号通路的影响

Decoction for reducing blood lipid and unblocking vessels improves blood lipid in hyperlipidemia rats via PERK/ATF4/CHOP signaling pathway

目的观察降脂通脉饮对高血脂症大鼠血脂及蛋白激酶样内质网激酶(PERK)/转录激活因子4(ATF4)/C/EBP同源蛋白(CHOP)信号通路的影响,探讨降脂通脉饮调节血脂的作用机制。方法将30只SD大鼠随机分为正常组、模型组及降脂通脉饮低、中、高剂量组,每组6只。正常组大鼠给予普通饲料喂养,同时灌胃生理盐水;其余组大鼠给予高脂饲料喂养,其中模型组同时灌胃生理盐水,降脂通脉饮低、中、高剂量组同时灌胃1.56 mg/(kg·d)、3.125 mg/(kg·d)、6.25 mg/(kg·d)的降脂通脉饮。连续干预8周后,生化法检测血清胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,RT-PCR和Western blot法检测颈动脉组织中PERK、ATF4、CHOPmRNA及蛋白表达情况。结果与正常组比较,模型组大鼠血清TC、TG、LDL-C水平和PERK、ATF4、CHOP mRNA及蛋白相对表达量均明显升高(P均<0.05);与模型组比较,降脂通脉饮中、高剂量组大鼠血清TC、TG、LDL-C水平和PERK、ATF4、CHOP mRNA及蛋白相对表达量均明显降低(P均<0.05)。结论降脂通脉饮可能通过调节内质网应激PERK/ATF4/CHOP信号通路而发挥降脂作用。

Objective It is to observe the effects of Decoction for reducing blood lipid and unblocking vessels on blood liquid and protein kinase R-like endoplasmic reticulum kinase(PERK)/activating transcription factor 4(ATF4)/C/EBP homologous protein(CHOP)signaling pathway in hyperlipidemia rats,and to explore the mechanism of this decoction in regulating blood lipids.Methods Thirty SD rats were randomly divided into normal group,model group,and the low,medium,and high dose groups of Decoction for reducing blood lipid and unblocking vessels,with 6 rats in each group.The rats in the normal group were fed with normal chow and given normal saline by gavage;the rats in the remaining groups were fed with high-fat chow,the ones of the model group were gavaged with normal saline by gavage,and the low,medium,and high-dose groups of Decoction for reducing blood lipid and unblocking vessels were gavaged with Decoction for reducing blood lipid and unblocking vessels 1.56 mg/(kg·d),3.125 mg/(kg·d),and 6.25 mg/(kg·d).After 8 weeks of continuous intervention,the serum levels of cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured by biochemical methods,and the expressions of PERK,ATF4,and CHOP mRNAs and proteins in carotid artery tissue were detected by RT-PCR and Western blot.Results The serum levels of TC,TG,LDL-C and the relative expressions of PERK,ATF4,CHOP mRNAs and proteins in carotid artery tissue in the model group were significantly higher than those in the normal group(all P<0.05),and the serum levels of TC,TG,LDL-C and the relative expressions of PERK,ATF4,CHOP mRNAs and proteins in carotid artery tissue in the medium,and high dose groups of Decoction for reducing blood lipid and unblocking vessels were significantly lower than those in the model group(all P<0.05).Conclusion Decoction for reducing blood lipid and unblocking vessels can reduce blood lipid in hyperlipidemia rats via PERK/ATF4/CHOP signaling pathway.