Effect of Sanhuang Xiexintang in Inhibiting 7-Ketocholesterol-induced Endothelial Disfunctional by NIRP3 Inflammasome Pathway

Yi-ke LIN; Yin-yan XIE; Lin-zhe LUO; Xin-yue ZHENG; Yi-jia ZHENG; Yang CHEN

doi:10.13422/j.cnki.syfjx.20192401

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Effect of Sanhuang Xiexintang in Inhibiting 7-Ketocholesterol-induced Endothelial Disfunctional by NIRP3 Inflammasome Pathway

Classic Prescriptions | 更新时间：2021-02-09

- Effect of Sanhuang Xiexintang in Inhibiting 7-Ketocholesterol-induced Endothelial Disfunctional by NIRP3 Inflammasome Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 1, Pages: 31-36(2020)
- 作者机构：
  
  1.广州中医药大学　中药学院，广州　 510006
  2.广州中医药大学　基础医学院，广州　 510006
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20192401
  CLC： R2-0; R22; R285.5; R289
- Received：15 May 2019，
  
  Published Online：06 September 2019，
  
  Published：05 January 2020
- 稿件说明：
移动端阅览
Yi-ke LIN, Yin-yan XIE, Lin-zhe LUO, et al. Effect of Sanhuang Xiexintang in Inhibiting 7-Ketocholesterol-induced Endothelial Disfunctional by NIRP3 Inflammasome Pathway[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 31-36.
DOI：

Yi-ke LIN, Yin-yan XIE, Lin-zhe LUO, et al. Effect of Sanhuang Xiexintang in Inhibiting 7-Ketocholesterol-induced Endothelial Disfunctional by NIRP3 Inflammasome Pathway[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 31-36. DOI： 10.13422/j.cnki.syfjx.20192401.

摘要

目的：

研究三黄泻心汤(SHXXT)能否通过抑制7-酮基胆固醇(7-keto)诱导的血管内皮细胞NOD样受体蛋白3(NLRP3)活化恢复内皮功能。

方法：

培养小鼠主动脉血管环组织，实验组分为正常组，模型7-keto组，三黄泻心汤含药血清1%，2%，5%不同浓度给药组，观察小鼠血管舒张功能；培养微血管内皮细胞，按照上述实验分组，另设置NLRP3抑制剂异甘草素(ISO)，通过蛋白免疫印迹法(Western blot)检测内皮一氧化氮合酶(eNOS)，NLRP3，含半胱氨酸的天冬氨酸蛋白水解酶-1(Caspase-1)，白细胞介素-1

(IL-1

)蛋白表达量的变化，除此之外，利用一氧化氮(NO)定量试剂盒检测NO的浓度。

结果：

与正常组比较，模型组显著降低血管环内皮依赖性舒张功能(

0.01)，给药组明显恢复内皮依赖性血管舒张功能，且成浓度依赖性(

0.05，

0.01)；同时研究显示，与正常组比较，模型组微血管内皮细胞eNOS蛋白表达明显降低(

0.05)，NLRP3，Caspase-1，IL-1

蛋白表达明显升高(

0.05，

0.01)，NO浓度显著降低(

0.01)；与模型组比较，给予三黄泻心汤血清治疗后，明显升高eNOS蛋白表达和NO浓度，明显降低NLRP3，Caspase-1，IL-1

蛋白表达(

0.05，

0.01)。

结论：

三黄泻心汤能改善7-keto引起的内皮依赖性血管功能损伤，且是通过抑制内皮NLRP3炎症小体活化介导的NO信号通路实现的。

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-1

(IL-1

) 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 (

0.01)

and the drug group significantly restored the endothelium-dependent vasodilation function in a concentration-dependent manner (

0.05

0.01). Meanwhile

microvascular endothelial cells were also studied. Compared with the normal group

the content of eNOS protein in the model group decreased (

0.05)

while the concentration of NO decreased significantly (

0.01). After treatment with SHXXT serum

eNOS and NO could be restored

with significant differences in the concentration of NO with 5% (

0.05) and 10% (

0.01) SHXXT serum. At the same time

the expressions of NIRP3 (

0.05)

cle-Caspase-1 activation (

0.01) and IL-1

production (

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 (

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.

关键词

Keywords

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