摘要
目的:观察中药复方冠心康及其拆方对LDLR^-/-动脉粥样硬化小鼠PERK-eIF2α-ATF4信号通路的影响,探讨冠心康对动脉粥样硬化的调节机制,并通过拆方研究,丰富冠心康调控动脉粥样硬化的中医理论。方法:生化法检测各组小鼠血脂含量;HE染色观察主动脉病理形态变化;RT-PCR、Western Blot方法检测主动脉相关蛋白和基因的表达。结果:冠心康对TG、TC具有显著的下调作用,对HDL-C的上调作用显著(P<0.05);冠心康全方可显著下调小鼠主动脉的ATF4基因和蛋白的表达(P<0.05),上调Bcl-2基因和蛋白的表达(P<0.05),并能抑制PERK、eIF2α蛋白磷酸化(P<0.05)。而各拆方组总体效果不如冠心康明显,但对血脂的不同指标、主动脉的基因和蛋白的表达以及主动脉的组织形态具有不同程度的作用。结论:冠心康可抑制内质网应激PERKeIF2α-ATF4信号通路,增加抗凋亡因子Bcl-2的表达,从而缓解动脉粥样硬化,其中具有益气化痰作用的拆方一组对抑制PERK-eIF2α-ATF4信号通路具有更重要的作用。
Objective: To observe the effects of Chinese herbal compound Guanxinkang(Gxk) and its decomposed formulas on PERK-eIF2α-ATF4 signaling pathway in LDLR^-/- atherosclerotic mice, and to explore the regulation mechanisms of Gxk on atherosclerosis and clarify the theory of traditional Chinese medicine in the treatment of atherosclerosis by Gxk. Methods: The blood lipid content of each group was detected by biochemical method. The pathological changes of aorta were observed by HE staining. The expression of aorta-associated protein and gene was detected by RT-PCR and Western Blot. Results: Gxk can regulate blood lipids, has obvious down-regulation effect on TG and TC, and significant effect on HDL-C up-regulation(P<0.05). Gxk can down-regulate the expression of gene and protein ATF4 in mouse aorta and up-regulate Bcl-2(P<0.05). And Gxk can inhibit the phosphorylation of PERK and eIF2α protein(P<0.05). The results of HE staining showed that in the Gxk and its decomposed group, the aortic plaque was smaller and the vascular structure was more complete in the Gxk group. The overall effects of each split groups are not as obvious as that of Gxk, but it has different effects on blood lipids, gene and protein expression of aorta and aortic tissue morphology. Conclusion: Guanxinkang can inhibit the endoplasmic reticulum stress PERKeIF2α-ATF4 signaling pathway, increase the expression of anti-apoptotic factor Bcl-2, and thereby alleviate atherosclerosis. Among them, the decomposed group1 with the effect of replenishing qi and resolving phlegm can inhibit The PERK-eIF2α-ATF4 signaling pathway has a more important role.
作者
马贵萍
陈冉
章怡祎
MA Gui-ping;CHEN Ran;ZHANG Yi-yi(Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2020年第9期4357-4362,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81302928)。
