Effect of Sanhuang Xiexintang in Inhibiting 7-Ketocholesterol-induced Endothelial Disfunctional by NIRP3 Inflammasome Pathway
10.13422/j.cnki.syfjx.20192401
- VernacularTitle:三黄泻心汤抑制危险脂肪因子7-keto诱导血管内皮NLRP3活化引起的功能紊乱的机制分析
- Author:
Yi-ke LIN
1
;
Yin-yan XIE
2
;
Lin-zhe LUO
1
;
Xin-yue ZHENG
1
;
Yi-jia ZHENG
1
;
Yang CHEN
1
Author Information
1. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
2. School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
- Publication Type:Research Article
- Keywords:
hyperlipidemia;
endothelium;
Sanhuang Xiexintang;
NOD-like receptor protein 3 (NIRP3);
endothelial nitric oxide synthase (eNOS);
vasodilation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2020;26(1):31-36
- CountryChina
- Language:Chinese
-
Abstract:
Objective::To study whether Sanhuang Xiexintang (SHXXT) can restore endothelial function by inhibiting the activation of NOD-like receptor protein 3 (NIRP3) induced by 7-ketocholesterol (7-keto) in vascular endothelial cells. Method::The aortic rings of mice were cultured in normal group, model (7-keto) group, SHXXT groups (1%, 2% and 5% drug-containing serum). Vasodilation function of mice was observed. Microvascular endothelial cells were cultured according to the above experimental groups, and NIRP3 inhibitor isoglycyrrhizin (ISO) group, was also set. Western blot was used to detect the expressions of endothelial nitric oxide synthase (eNOS), NIRP3, cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin-1β (IL-1β) protein. In addition, nitric oxide (NO) quantitative kit was used to detect the concentration of NO. Result::Compared with the normal group, the endothelium-dependent vasodilation function of vascular rings was significantly reduced in model group (P<0.01), and the drug group significantly restored the endothelium-dependent vasodilation function in a concentration-dependent manner (P<0.05, P<0.01). Meanwhile, microvascular endothelial cells were also studied. Compared with the normal group, the content of eNOS protein in the model group decreased (P<0.05), while the concentration of NO decreased significantly (P<0.01). After treatment with SHXXT serum, eNOS and NO could be restored, with significant differences in the concentration of NO with 5% (P<0.05) and 10% (P<0.01) SHXXT serum. At the same time, the expressions of NIRP3 (P<0.05), cle-Caspase-1 activation (P<0.01) and IL-1β production (P<0.01) in endothelium were significantly increased under 7-keto stimulation, and the SHXXT serum could significantly inhibit the expression and activation of relevant proteins. Subsequently, endothelial cells were treated with NIRP3 inhibitor ISO. Compared with the model group, eNOS expression increased, and NO concentration increased significantly (P<0.01) after treatment with ISO, but ISO had no synergistic effect on SHXXT serum. Conclusion::SHXXT can improve endothelium-dependent vascular dysfunction induced by 7-keto, which is achieved by NO signaling pathway mediated by inhibiting the activation of endothelial NIRP3-related proteins.
