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.
作者
雎世聪
邹旭峰
王元红
龙飘
郁保生
JU Shi-cong;ZOU Xu-feng;WANG Yuan-hong;LONG Piao;YU Bao-sheng(Hunan University of Chinese Medicine,Changsha 410000,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
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)~~
