冠心平片通过抑制激活的PI3K/Akt/NF-κB信号级联反应抑制ET-1诱导的MOVAS增殖和迁移。

Guanxinping Tablets Inhibit ET-1-Induced Proliferation and Migration of MOVAS by Suppressing Activated PI3K/Akt/NF-B Signaling Cascade.

作者信息

Wu Ying-Ying, Huang Yi-Lin, Dai Bin, Liu Jian-Wei, Han Xu

机构信息

Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215000, China.

Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

出版信息

Evid Based Complement Alternat Med. 2022 May 31;2022:9485463. doi: 10.1155/2022/9485463. eCollection 2022.

DOI:10.1155/2022/9485463

PMID:35685734

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9173997/

Abstract

BACKGROUND/AIM: Abnormal proliferation and migration of vascular smooth muscle cells is one of the main causes of (AS). Therefore, the suppression of abnormal proliferation and migration of smooth muscle cells are the important means for the prevention and inhibition of AS. The clinical effects of Guanxinping (GXP) tablets and preliminary clinical research on the topic have proved that GXP can effectively treat coronary heart disease, but its underlying mechanism remains unclear. This study aimed to confirm the inhibitory effect of GXP on the abnormal proliferation of mouse aortic vascular smooth muscle (MOVAS) cells and to explore the underlying mechanism.

METHODS

MOVAS cells were divided into two major groups: physiological and pathological groups. In the physiological group, MOVAS cells were directly stimulated with GXP, whereas in the pathological group, the cells were stimulated by endothelin-1 (ET-1) before intervention by GXP. At the same time, atorvastatin calcium, which effectively inhibits the abnormal proliferation of MOVAS cells, was used in the negative control group. CCK8 assay, scratch test, ELISA, Western blotting, and immunofluorescence staining were performed to observe the proliferation and migration of MOVAS cells and the expression levels of related factors after drug intervention in each group.

RESULTS

In the physiological group, GXP had no significant effect on the proliferation and migration of MOVAS cells and the related factors. In the pathological group, a high dose of GXP reduced the abnormal proliferation and migration of MOVAS cells. Further, it reduced the expression levels of PI3K; inhibited the phosphorylation of Akt (protein kinase B); upregulated IB- levels; prevented nuclear factor kappa B (NF-B) from entering the nucleus; downregulated the expression of interleukin 6 (IL6), IL-1, and iNOS; and upregulated the ratio of apoptosis-related factor Bax/Bcl-2. There was no significant difference between the high-dose GXP group and the atorvastatin calcium group (negative control group).

CONCLUSION

Our findings revealed that GXP was able to inhibit the proliferation and migration of MOVAS cells by regulating the PI3K/Akt/NF-B pathway.

摘要

背景/目的：血管平滑肌细胞的异常增殖和迁移是动脉粥样硬化（AS）的主要原因之一。因此，抑制平滑肌细胞的异常增殖和迁移是预防和抑制AS的重要手段。冠心平（GXP）片的临床疗效及对此课题的初步临床研究已证明，GXP可有效治疗冠心病，但其潜在机制尚不清楚。本研究旨在证实GXP对小鼠主动脉血管平滑肌（MOVAS）细胞异常增殖的抑制作用，并探讨其潜在机制。

方法

将MOVAS细胞分为两大组：生理组和病理组。生理组中，MOVAS细胞直接用GXP刺激，而病理组中，细胞在GXP干预前用内皮素-1（ET-1）刺激。同时，在阴性对照组中使用能有效抑制MOVAS细胞异常增殖的阿托伐他汀钙。采用CCK8法、划痕试验、酶联免疫吸附测定（ELISA）、蛋白质印迹法和免疫荧光染色，观察每组药物干预后MOVAS细胞的增殖、迁移及相关因子的表达水平。

结果

生理组中，GXP对MOVAS细胞的增殖、迁移及相关因子无显著影响。病理组中，高剂量GXP可降低MOVAS细胞的异常增殖和迁移。此外，它降低了磷脂酰肌醇-3激酶（PI3K）的表达水平；抑制了蛋白激酶B（Akt）的磷酸化；上调了IκB水平；阻止核因子κB（NF-κB）进入细胞核；下调了白细胞介素6（IL-6）、白细胞介素-1（IL-1）和诱导型一氧化氮合酶（iNOS）的表达；并上调了凋亡相关因子Bax/Bcl-2的比值。高剂量GXP组与阿托伐他汀钙组（阴性对照组）之间无显著差异。