基于TLR-2/4-IRF3信号通路研究四逆汤抗动脉粥样硬化的机制  

Study on the mechanism of Sini Decoction against atherosclerosis based on TLR-2/4-IRF3 signaling pathway

作　　者：雎世聪 邹旭峰[1] 王元红[1] 龙飘 郁保生[1] JU Shi-cong;ZOU Xu-feng;WANG Yuan-hong;LONG Piao;YU Bao-sheng(Hunan University of Chinese Medicine,Changsha 410000,China)

机构地区：[1]湖南中医药大学

出　　处：《中华中医药杂志》2019年第11期5470-5474,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81373716);湖南省中医药管理局项目(No.201518);湖南省研究生创新课题(No.CX2017B429)~~

摘　　要：目的:从TLR-2/4-IRF3信号传导通路的角度,观察四逆汤对动脉粥样硬化(AS)的影响,从蛋白分子水平探讨四逆汤促胆固醇逆转运抗AS形成的作用机制。方法:将60只AS模型家兔随机分为空白对照组,模型组,阿托伐他汀组,四逆汤低、中、高剂量组,观察各组家兔主动脉形态,比较各组家兔治疗后血清中TC、TG、LDL-C、HDL-C、ApoA1、Apo-B水平的变化,以及腹主动脉TLR-2、TLR-4、IRF3和ABCA1蛋白表达变化,并在ox-LDL诱导的巨噬细胞上检测四逆汤对TLR-2、TLR-4、IRF3和ABCA1表达水平的干预作用。结果:阿托伐他汀组、四逆汤组对泡沫细胞的形成、VSMCS增殖都有抑制作用。与空白对照组比较,模型组血清TC、TG、LDL-C、Apo-B均表达升高,HDL-C、ApoA1表达降低(P<0.01),各治疗组TC、TG、Apo-B均较模型组降低(P<0.05,P<0.01);血清HDL-C、ApoA1显著升高(P<0.05,P<0.01)。模型组兔腹主动脉ABCA1蛋白表达较空白对照组降低,TLR-2、TLR-4与IRF3蛋白表达升高,各治疗组的ABCA1蛋白表达升高,TLR-2、TLR-4与IRF3蛋白表达降低(P<0.05,P<0.01)。在泡沫化巨噬细胞上,也发现四逆汤可以逆转TLR-2、TLR-4和ABCA1在细胞膜上的平均荧光强度表达,并且下调IRF3蛋白水平。结论:四逆汤能够抑制TLR-2/4-IRF3信号通路,上调ABCA1表达,从而促进胆固醇逆转运达到抗AS的作用,这可能是四逆汤治疗AS的机制之一。Objective: To observe the effects of Sini Decoction on atherosclerosis(AS) through TLR-2/4-IRF3 signaling pathway, and to investigate its mechanism in anti-AS by promoting the reverse cholesterol transport. Methods: Sixty rabbits were divided randomly into 6 groups including control group, AS group without treatment, AS group with atorvastatin treatment, AS group with low-dose Sini decoction treatment, AS group with medium-dose Sini decoction treatment, and AS group with high-dose Sini decoction treatment. HE staining was used for the aortic morphologies. The levels of TC, TG, LDL-C, HDL-C, ApoA1 and Apo-B in serum were compared between groups. And the protein expressions of TLR-2, TLR-4, IRF3 and ABCA1 in abdominal aorta were detected by Western Blot. Results: Both atorvastatin and Sini decoction could inhibit the formation of foam cells and VSMCS proliferation. In AS rabbits, the serum TC, TG, LDL-C and Apo-B were increased, whereas serum HDL-C and ApoA1 were decreased(P<0.01). Compared with AS group, the serum TC, TG and Apo-B were significantly decreased(P<0.05, P<0.01), whereas serum HDL-C and ApoA1 were increased in both atorvastatin-treated or Sini-decoction-treated groups(P<0.05, P<0.01). Compared with AS group, ABCA1 protein level were significantly increased, whereas TLR-2, TLR-4 and IRF3 level decreased in abdominal aorta of drug-treated AS rabbits(P<0.05, P<0.01). In addition, Sini decoction presented the reversed effect on ox-LDL-induced upregulation of TLR-2, TLR-4, IRF3, and ABCA1 downregulation in macrophage foam cells. Conclusion: Sini Decoction increases the expression of ABCA1 through inhibiting TLR-2/4-IRF3 signal pathway, thus to promote the reverse cholesterol transport and prevent AS. It might be the mechanism of Sini Decoction in treating AS.

关 键 词：四逆汤 动脉粥样硬化 三磷酸腺苷结合盒转体1 TOLL样受体2 Toll样受体4 干扰素调节因子3 

分 类 号：R54[医药卫生—心血管疾病]