槐果碱通过抑制大鼠模型中的炎症减轻损伤诱导的颈动脉内膜增生。

Sophocarpine Alleviates Injury-Induced Intima Hyperplasia of Carotid Arteries by Suppressing Inflammation in a Rat Model.

作者信息

Yang Genhuan, Zeng Rong, Song Xitao, Liu Changwei, Ni Leng

机构信息

Department of Vascular Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

出版信息

J Clin Med. 2021 Nov 22;10(22):5449. doi: 10.3390/jcm10225449.

DOI:10.3390/jcm10225449

PMID:34830730

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8625628/

Abstract

INTRODUCTION

Balloon angioplasty is a commonly applied procedure for treating atherosclerotic vascular diseases. However, the maintenance of long-term lumen patency is relatively difficult due to the occurrence of restenosis. Previous research has shown that the occurrence of vascular wall inflammation is associated with higher rates of restenosis. Sophocarpine (SPC) can exert various therapeutic effects such as anti-oxidation, anti-inflammation, anti-tumor, antivirus and immune regulation. This study aimed to investigate whether SPC can alleviate intimal hyperplasia following balloon injury in a rat carotid artery model.

METHODS

Twenty Sprague-Dawley rats were randomly assigned to four groups: (i) control, (ii) balloon injury, (iii) balloon injury followed by saline injection, and (iv) balloon injury followed by SPC administration. Each group contained five rats. A high-pressure balloon of 3 mm × 20 mm was placed in the carotid artery. The balloon was inflated to a pressure of 8 atmospheres to carry out rat carotid artery balloon injury model. The areas of neointimal and media were determined by Verhoeff_Van Gieson staining, and the intima-to-media (I:M) ratios were subsequently evaluated. After that, the protein levels of IL-6, IL-1β, MCP-1, NF-κB, TNF-α, VCAM-1, ICAM-1 and eNOS were measured.

RESULTS

The ratio of I:M was remarkably higher in the balloon injury group than in the control group ( < 0.01). SPC could significantly decrease the ratio of I:M compared with the balloon injury group ( < 0.01). Besides, the protein levels of IL-6, IL-1β, MCP-1, NF-κB, TNF-α, ICAM-1 and VCAM-1 were increased in rat carotid arteries exposed to balloon injury ( < 0.01), and treatment with SPC could attenuate these effects ( < 0.05). Furthermore, balloon injury inhibited the protein expression of eNOS ( < 0.01), and SPC could elevate its level ( < 0.05).

CONCLUSIONS

SPC could alleviate an intimal hyperplasia in balloon-injured carotid artery, and the mechanisms underlying this protective effect might be due to its inhibitory potency against inflammation signals. Our study also implies the potential applicability of SPC in treating restenosis after balloon angioplasty.

摘要

引言

球囊血管成形术是治疗动脉粥样硬化性血管疾病的常用方法。然而，由于再狭窄的发生，长期维持管腔通畅相对困难。先前的研究表明，血管壁炎症的发生与较高的再狭窄率相关。槐果碱（SPC）具有多种治疗作用，如抗氧化、抗炎、抗肿瘤、抗病毒和免疫调节。本研究旨在探讨SPC是否能减轻大鼠颈动脉球囊损伤后的内膜增生。

方法

将20只Sprague-Dawley大鼠随机分为四组：（i）对照组，（ii）球囊损伤组，（iii）球囊损伤后注射生理盐水组，（iv）球囊损伤后给予SPC组。每组包含5只大鼠。将一个3 mm×20 mm的高压球囊置于颈动脉中。将球囊充气至8个大气压以建立大鼠颈动脉球囊损伤模型。通过Verhoeff_Van Gieson染色确定新生内膜和中膜的面积，随后评估内膜与中膜（I:M）比值。之后，测量白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、单核细胞趋化蛋白-1（MCP-1）、核因子κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）和内皮型一氧化氮合酶（eNOS）的蛋白水平。

结果

球囊损伤组的I:M比值显著高于对照组（<0.01）。与球囊损伤组相比，SPC可显著降低I:M比值（<0.01）。此外，暴露于球囊损伤的大鼠颈动脉中IL-6、IL-1β、MCP-1、NF-κB、TNF-α、ICAM-1和VCAM-1的蛋白水平升高（<0.01），而SPC治疗可减弱这些作用（<0.05）。此外，球囊损伤抑制了eNOS的蛋白表达（<0.01），而SPC可提高其水平（<0.05）。