Wang Xuan, Hu Yue-Cheng, Zhang Ru-Yan, Jin Dong-Xia, Jiang Yuan, Zhang He-Nan, Cong Hong-Liang
Cardiology Department, Tianjin Medical University, Tianjin 300070, P.R. China; Cardiology Department, Tianjin Chest Hospital, Tianjin 300222, P.R. China.
Cardiology Department, Tianjin Chest Hospital, Tianjin 300222, P.R. China.
Exp Ther Med. 2016 Nov;12(5):3242-3248. doi: 10.3892/etm.2016.3775. Epub 2016 Oct 4.
The present study aimed to investigate the effect of cyclosporin A (CSA) intervention on the immunological mechanisms underlying coronary heart disease (CHD) and restenosis (RS) in rabbits. A total of 48 rabbits were randomly divided into normal control (N), N + CSA, CHD model, CHD + CSA, RS model and RS + CSA groups. Rabbits in the respective groups received different treatments prior to sacrifice at the end of week 12. Iliac arteries were harvested from the rabbits for morphological analysis and to determine the mRNA and protein expression levels of cluster of differentiation (CD) 40/CD40 ligand (CD40L), CD134/CD134 ligand (CD134L) and inflammatory factors, including matrix metalloproteinase (MMP)-1, MMP-9, vascular cell adhesion protein (VCAM)-1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, by reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. As compared with the N group, the mRNA expression levels of MMP-9, VCAM-1 and TNF-α were significantly increased in the CHD and RS groups (P<0.05), but were significantly decreased in the groups with CSA intervention, as compared with those without CSA intervention (P<0.05). Conversely, there were no significant differences in the expression levels of MMP-1 and IL-6 among the six groups, although a decreasing trend of IL-6 expression was observed following intervention with CSA. Furthermore, there were significant differences in the mRNA and protein expression levels of CD40/CD40L and CD134/CD134L among the N, CHD and RS groups (P<0.05), and between the groups with and without CSA intervention. The present study demonstrated that CSA intervention exerted beneficial effects on CHD and RS, and further studies are required to investigate the mechanisms underlying the effects of CSA on CHD.
本研究旨在探讨环孢素A(CSA)干预对兔冠心病(CHD)及再狭窄(RS)免疫机制的影响。将48只兔随机分为正常对照组(N)、N + CSA组、CHD模型组、CHD + CSA组、RS模型组和RS + CSA组。各组兔在第12周结束时处死前接受不同处理。采集兔髂动脉进行形态学分析,并通过逆转录定量聚合酶链反应和免疫组织化学染色测定分化簇(CD)40/CD40配体(CD40L)、CD134/CD134配体(CD134L)及炎性因子,包括基质金属蛋白酶(MMP)-1、MMP-9、血管细胞黏附蛋白(VCAM)-1、白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α的mRNA和蛋白表达水平。与N组相比,CHD组和RS组中MMP-9、VCAM-1和TNF-α的mRNA表达水平显著升高(P<0.05),但与未进行CSA干预的组相比,CSA干预组中这些指标显著降低(P<0.05)。相反,六组中MMP-1和IL-6的表达水平无显著差异,尽管CSA干预后IL-6表达呈下降趋势。此外,N组、CHD组和RS组之间以及CSA干预组与未干预组之间CD40/CD40L和CD134/CD134L的mRNA和蛋白表达水平存在显著差异(P<0.05)。本研究表明,CSA干预对CHD和RS具有有益作用,需要进一步研究来探讨CSA对CHD作用的机制。