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Effect of Sanhuang Xiexintang in Inhibiting 7-Ketocholesterol-induced Endothelial Disfunctional by NIRP3 Inflammasome Pathway / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 31-36, 2020.
Article in Chinese | WPRIM | ID: wpr-862689
ABSTRACT
<b>

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. <b>

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-1<italic>β</italic> (IL-1<italic>β</italic>) protein. In addition, nitric oxide (NO) quantitative kit was used to detect the concentration of NO. <b>

Result:

Compared with the normal group, the endothelium-dependent vasodilation function of vascular rings was significantly reduced in model group (<italic>P</italic><0.01), and the drug group significantly restored the endothelium-dependent vasodilation function in a concentration-dependent manner (<italic>P</italic><0.05, <italic>P</italic><0.01). Meanwhile, microvascular endothelial cells were also studied. Compared with the normal group, the content of eNOS protein in the model group decreased (<italic>P</italic><0.05), while the concentration of NO decreased significantly (<italic>P</italic><0.01). After treatment with SHXXT serum, eNOS and NO could be restored, with significant differences in the concentration of NO with 5% (<italic>P</italic><0.05) and 10% (<italic>P</italic><0.01) SHXXT serum. At the same time, the expressions of NIRP3 (<italic>P</italic><0.05), cle-Caspase-1 activation (<italic>P</italic><0.01) and IL-1<italic>β</italic> production (<italic>P</italic><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 (<italic>P</italic><0.01) after treatment with ISO, but ISO had no synergistic effect on SHXXT serum. <b>

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.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2020 Type: Article