發(fā)布時(shí)間：2018-05-18 21:11

  本文選題：IL-32γ + 動(dòng)脈粥樣硬化　； 參考：《華中科技大學(xué)》2011年碩士論文

【摘要】：動(dòng)脈粥樣硬化(atherosclerosis, AS)及其并發(fā)癥如中風(fēng)、心肌梗塞、腦溢血等是嚴(yán)重危害人類健康的常見疾病。動(dòng)脈粥樣硬化主要累及大、中動(dòng)脈,是多種因素綜合作用的結(jié)果。研究表明,血管平滑肌細(xì)胞(vascular smooth muscle cells ,VSMC)的增殖和向內(nèi)膜的遷移以及凋亡是動(dòng)脈粥樣硬化(AS)及其并發(fā)癥發(fā)生發(fā)展過(guò)程中的一個(gè)關(guān)鍵因素。近年研究顯示,動(dòng)脈粥樣硬化本質(zhì)上是一種慢性免疫炎性疾病,炎性因子在動(dòng)脈粥樣硬化及其并發(fā)癥的發(fā)生與發(fā)展過(guò)程中起著重要作用,因而炎性因子對(duì)VSMC增殖、遷移、分泌和凋亡作用也就自然成為國(guó)內(nèi)外學(xué)者關(guān)注的課題。 IL-32(interleukin 32)是在自然殺傷細(xì)胞(natural killer cell, NK)中新發(fā)現(xiàn)的一種致炎細(xì)胞因子。幾年來(lái)的研究發(fā)現(xiàn),IL-32可通過(guò)多條信號(hào)傳導(dǎo)途徑,促進(jìn)細(xì)胞分化,參與細(xì)胞凋亡,誘導(dǎo)其他致炎細(xì)胞因子和趨化因子的生成等,在炎癥反應(yīng)和自身免疫性疾病等方面發(fā)揮著重要作用。 鑒于IL-32是一種重要致炎細(xì)胞因子及致炎細(xì)胞因子和趨化因子的誘導(dǎo)劑,且在類風(fēng)濕關(guān)節(jié)炎中發(fā)揮重要作用,而類風(fēng)濕關(guān)節(jié)炎又具有加速動(dòng)脈粥樣硬化特性,據(jù)此我們推測(cè),IL-32可能對(duì)VSMC的增殖、遷移、凋亡和分泌發(fā)揮調(diào)節(jié)作用,并可能成為動(dòng)脈粥樣硬化防治的一個(gè)重要新靶標(biāo)。因而探索研究IL-32在動(dòng)脈粥樣硬化中的生物學(xué)功能及其分子機(jī)制,對(duì)于揭示IL-32在動(dòng)脈粥樣硬化病理演變中的功能地位、設(shè)計(jì)合理的治療藥物,進(jìn)一步提高動(dòng)脈粥樣硬化疾病的治療水平可能具有重要科學(xué)與臨床意義。 本實(shí)驗(yàn)以離體培養(yǎng)的Wistar大鼠胸主動(dòng)脈血管平滑肌細(xì)胞為研究材料,利用MTT(multiply-table tournament)法檢測(cè)不同濃度IL-32γ(10,50,100 ng/ml)對(duì)VSMC細(xì)胞活力的影響。通過(guò)流式細(xì)胞術(shù)檢測(cè)IL-32以及加入NF-кB和MAPKs信號(hào)通路各抑制劑(PDTC是NF-κB抑制劑,PD98059是ERK1/2特異性抑制劑,SB203580是p38MAPK特異性抑制劑,SP600125是JNK特異性抑制劑)后對(duì)VSMC周期及其凋亡的影響。RT-PCR檢測(cè)IGF-1、IGFBP-3、MMP-2、TIMP-1的mRNA的表達(dá).通過(guò)實(shí)驗(yàn)研究,發(fā)現(xiàn)IL-32γ有促進(jìn)細(xì)胞增殖、遷移和抑制細(xì)胞凋亡的作用。說(shuō)明IL-32γ有加速動(dòng)脈粥樣硬化的作用。
[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 緯 (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 緯 could promote cell proliferation, migration and inhibit apoptosis. The results showed that IL-32 緯 could accelerate atherosclerosis.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R363

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 張秀云,徐輝,任麗群;大鼠主動(dòng)脈平滑肌細(xì)胞體外培養(yǎng)及其臨床意義[J];吉林醫(yī)學(xué);2003年01期

2 鄭銘,張幼怡,韓啟德;β腎上腺素受體的絲裂原活化蛋白激酶信號(hào)途徑[J];生理科學(xué)進(jìn)展;2002年02期

3 鄭仲承;寡核苷酸的優(yōu)化設(shè)計(jì)[J];生命的化學(xué);2001年03期

4 魯衍強(qiáng),葉其壯;基質(zhì)金屬蛋白酶及其抑制劑[J];生命的化學(xué);2002年04期

5 蔡琪,李曉玫;絲裂原活化蛋白激酶信號(hào)轉(zhuǎn)導(dǎo)通路研究進(jìn)展[J];腎臟病與透析腎移植雜志;1999年04期

6 郭曉綱,陳君柱,朱建華,鄭良榮,張芙榮,陶謙民,張蕓;過(guò)氧化氫對(duì)血管平滑肌細(xì)胞增殖和明膠酶A及其抑制因子基因表達(dá)的影響[J];中國(guó)病理生理雜志;2002年12期

7 程翔,廖玉華;炎癥與動(dòng)脈粥樣硬化[J];中華心血管病雜志;2004年05期

8 景濤,劉建平,何國(guó)祥,吳昊,王海東;組織貼壁法培養(yǎng)大鼠主動(dòng)脈平滑肌細(xì)胞的探討[J];中國(guó)現(xiàn)代醫(yī)學(xué)雜志;2001年09期

9 吳冬;歐俊;惠寧;;絲裂原激活的蛋白激酶(MAPK)信號(hào)轉(zhuǎn)導(dǎo)通路與卵巢上皮癌[J];腫瘤;2007年08期

，

本文編號(hào)：1907225