细胞因子IL-32γ对大鼠血管平滑肌细胞增殖、凋亡和分泌的功能研究

发布时间：2018-05-18 21:11

本文选题：IL-32γ + 动脉粥样硬化　；参考：《华中科技大学》2011年硕士论文

【摘要】：动脉粥样硬化(atherosclerosis, AS)及其并发症如中风、心肌梗塞、脑溢血等是严重危害人类健康的常见疾病。动脉粥样硬化主要累及大、中动脉,是多种因素综合作用的结果。研究表明,血管平滑肌细胞(vascular smooth muscle cells ,VSMC)的增殖和向内膜的迁移以及凋亡是动脉粥样硬化(AS)及其并发症发生发展过程中的一个关键因素。近年研究显示,动脉粥样硬化本质上是一种慢性免疫炎性疾病,炎性因子在动脉粥样硬化及其并发症的发生与发展过程中起着重要作用,因而炎性因子对VSMC增殖、迁移、分泌和凋亡作用也就自然成为国内外学者关注的课题。 IL-32(interleukin 32)是在自然杀伤细胞(natural killer cell, NK)中新发现的一种致炎细胞因子。几年来的研究发现,IL-32可通过多条信号传导途径,促进细胞分化,参与细胞凋亡,诱导其他致炎细胞因子和趋化因子的生成等,在炎症反应和自身免疫性疾病等方面发挥着重要作用。鉴于IL-32是一种重要致炎细胞因子及致炎细胞因子和趋化因子的诱导剂,且在类风湿关节炎中发挥重要作用,而类风湿关节炎又具有加速动脉粥样硬化特性,据此我们推测,IL-32可能对VSMC的增殖、迁移、凋亡和分泌发挥调节作用,并可能成为动脉粥样硬化防治的一个重要新靶标。因而探索研究IL-32在动脉粥样硬化中的生物学功能及其分子机制,对于揭示IL-32在动脉粥样硬化病理演变中的功能地位、设计合理的治疗药物,进一步提高动脉粥样硬化疾病的治疗水平可能具有重要科学与临床意义。本实验以离体培养的Wistar大鼠胸主动脉血管平滑肌细胞为研究材料,利用MTT(multiply-table tournament)法检测不同浓度IL-32γ(10,50,100 ng/ml)对VSMC细胞活力的影响。通过流式细胞术检测IL-32以及加入NF-кB和MAPKs信号通路各抑制剂(PDTC是NF-κB抑制剂,PD98059是ERK1/2特异性抑制剂,SB203580是p38MAPK特异性抑制剂,SP600125是JNK特异性抑制剂)后对VSMC周期及其凋亡的影响。RT-PCR检测IGF-1、IGFBP-3、MMP-2、TIMP-1的mRNA的表达.通过实验研究,发现IL-32γ有促进细胞增殖、迁移和抑制细胞凋亡的作用。说明IL-32γ有加速动脉粥样硬化的作用。
[Abstract]:Atherosclerotic atherosclerosis (ASS) and its complications such as stroke, myocardial infarction, cerebral haemorrhage are common diseases that seriously endanger human health. Atherosclerosis is mainly involved in the large, middle artery, is the result of a variety of factors. The study shows that the proliferation, migration to the intima and apoptosis of vascular smooth muscle cells (VSMC) are a key factor in the development of atherosclerosis and its complications. Recent studies have shown that atherosclerosis is essentially a chronic immune inflammatory disease. Inflammatory factors play an important role in the occurrence and development of atherosclerosis and its complications. Therefore, inflammatory factors play an important role in the proliferation and migration of VSMC. The role of secretion and apoptosis has naturally become a topic of concern to scholars at home and abroad. IL-32(interleukin 32) is a newly discovered inflammatory cytokine in natural killer cell, NK) of natural killer cells. In recent years, it has been found that IL-32 can promote cell differentiation, participate in apoptosis and induce the production of other inflammatory cytokines and chemokines through several signal transduction pathways. It plays an important role in inflammatory reaction and autoimmune disease. Since IL-32 is an important inducer of inflammatory cytokines, inflammatory cytokines and chemokines, and plays an important role in rheumatoid arthritis, rheumatoid arthritis has the characteristics of accelerating atherosclerosis. Therefore, we speculate that IL-32 may regulate the proliferation, migration, apoptosis and secretion of VSMC, and may become an important new target for the prevention and treatment of atherosclerosis. Therefore, to explore the biological function and molecular mechanism of IL-32 in atherosclerosis, to reveal the functional role of IL-32 in the pathological evolution of atherosclerosis, and to design reasonable therapeutic drugs. Further improving the treatment level of atherosclerosis may have important scientific and clinical significance. In this study, cultured vascular smooth muscle cells (VSMCs) of thoracic aorta of Wistar rats were used to study the effects of different concentrations of IL-32 纬 (1050ng / ml) on the activity of VSMC cells by MTT(multiply-table tournament assay. Flow cytometry was used to detect the effect of IL-32 on VSMC cycle and apoptosis after adding NF- 魏 B and MAPKs signal pathway inhibitors. PDTC is NF- 魏 B inhibitor p98059, a specific inhibitor of ERK1/2, SB203580 is a p38MAPK specific inhibitor and SP600125 is a JNK specific inhibitor. The mRNA expression of MMP-2 TIMP-1 in IGF-1 and IGFBP-3 was detected by RT-PCR. It was found that IL-32 纬 could promote cell proliferation, migration and inhibit apoptosis. The results showed that IL-32 纬 could accelerate atherosclerosis.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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