炎症因子介导cAMP-PKA通路作用下VSMCs表达骨相关蛋白与CAS斑块钙化的相关性研究

发布时间：2018-04-26 17:58

本文选题：慢性支气管炎 + 冠状动脉粥样硬化　；参考：《重庆医科大学》2017年硕士论文

【摘要】：第一部分机体慢性炎症与冠状动脉粥样硬化的相关性分析目的:从病理学角度探讨慢性炎症与冠状动脉粥样硬化(coronary atherosclerosis,CAS)的相关性。方法:回顾性分析涉及慢性炎症和(或)CAS患者的病历及尸体检验资料。结果:CAS合并一种及以上慢性炎症216例,其中男性159例(73.61%),女性57例(26.39%);左冠状动脉前降支最易发生粥样硬化及狭窄;CAS患者中慢性支气管炎(chronic bronchitis,CB)196例,CB与CAS呈正相关(rs=0.404,P=0.000),且是CAS发生的危险因素之一(OR=4.852,95%CI=2.898~8.124,P=0.000),其他慢性炎症如慢性肾盂肾炎、慢性胃肠炎、慢性食管炎、慢性淋巴细胞甲状腺炎及慢性宫颈炎与CAS均无明显相关性(P0.05)。结论:CB是CAS发生发展的危险因素之一;临床上应重视CB的治疗,从而降低冠心病的发生率和死亡率。第二部分炎症因子与骨相关蛋白表达及CAS斑块钙化的相关性研究目的:检测CAS斑块中钙盐相对含量,并检测斑块中白细胞介素-6(interleukin-6,IL-6)和骨相关蛋白,如骨钙蛋白(bone gla protein,BGP)、骨桥蛋白(osteopontin,OPN)及Runt相关转录因子2(runt-related transcription factor 2,RUNX2)的表达情况,探讨成骨表型细胞的来源、IL-6与骨相关蛋白表达及CAS斑块钙化的相关性。方法:以人体CAS斑块为研究对象,根据管腔狭窄程度将实验分为五组:正常组、I级狭窄组、II级狭窄组、III级狭窄组及IV级狭窄组。通过HE染色及特殊染色观察各组斑块的形态学改变,并分析钙盐相对含量;免疫组化检测成骨表型细胞的来源;免疫组化及Western Blot实验检测斑块中骨相关蛋白表达,并对IL-6与骨相关蛋白表达的相关性进行分析。结果:冠状动脉钙化率随管腔狭窄程度的增加而增加,II-IV级狭窄组可见不同程度钙盐沉积,且II-IV级狭窄组中钙盐相对含量差异有统计学意义(P0.05)。早期CAS斑块(I-II级狭窄组)成骨表型细胞主要来源于单核-巨噬细胞,而中晚期CAS斑块(III-IV级狭窄组)成骨表型细胞主要来源于血管平滑肌细胞(vascular smooth muscle cells,VSMCs)。IL-6、BGP、OPN及RUNX2表达随管腔狭窄程度的增加而增强,IL-6、BGP及RUNX2在I-IV级狭窄组均较正常组表达有统计学意义(P0.01),而OPN在II-IV级狭窄组均较正常组表达有统计学意义(P0.01)。蛋白激酶A(Protein kinase A,PKA)及环腺苷酸-反应元件结合蛋白(Cyclic adenosine monophosphate-response element binding protein,CREB)在II-IV级狭窄组较正常组表达有统计学意义(P0.01)。IL-6与骨相关蛋白(BGP、OPN及RUNX2)表达量均存在线性正相关(r值分别为0.790、0.986、0.919,P0.01)。结论:冠状动脉VSMCs在炎症因子介导c AMP-PKA通路作用下向成骨细胞表型转变及表达骨相关蛋白最终导致CAS斑块中钙盐沉积。
[Abstract]:Analysis of the correlation between chronic inflammation and coronary atherosclerosis in part 1 Objective: To investigate the correlation between chronic inflammation and coronary atherosclerosis (CAS) from a pathological point of view. Methods: a retrospective analysis of the records of patients with chronic inflammation and / or CAS and the data of cadavers. Results: CAS combined with one kind. There were 216 cases of chronic inflammation, including 159 males (73.61%) and 57 females (26.39%). Left anterior descending coronary artery was the most susceptible to atherosclerosis and stenosis, and 196 cases of chronic bronchitis (chronic bronchitis, CB) in CAS patients, CB and CAS (rs=0.404, P= 0), and one of the risk factors for CAS (OR=4.852,95%CI=2.898~8.124, P=0) .000), other chronic inflammation such as chronic pyelonephritis, chronic gastroenteritis, chronic esophagitis, chronic lymphocytic thyroiditis and chronic cervicitis have no significant correlation with CAS (P0.05). Conclusion: CB is one of the risk factors for the development of CAS; the treatment of CB should be paid attention to in clinical, so as to reduce the incidence and mortality of coronary heart disease. Second parts The correlation between inflammatory factors and bone related protein expression and CAS plaque calcification Objective: to detect the relative calcium salt content in CAS plaque, and to detect interleukin -6 (interleukin-6, IL-6) and bone associated protein in plaque, such as bone gla protein (BGP), bone bridge protein (osteopontin, OPN), and Runt related transcription factor 2 Anscription factor 2, RUNX2) expression, the origin of osteoblast phenotype cells, the correlation between IL-6 and bone related protein expression and CAS plaque calcification. Methods: the human CAS plaque as the research object, according to the degree of stenosis of the lumen, the experiment is divided into five groups: normal group, I stricture group, II stricture group, III stricture group and IV stricture group. The morphological changes of plaque in each group were observed by HE staining and special staining, and the relative content of calcium salt was analyzed; the source of osteoblast phenotype was detected by immunohistochemistry; the expression of bone related protein in plaque was detected by immunohistochemistry and Western Blot, and the correlation between the expression of IL-6 and bone related protein was analyzed. The increase in the degree of stenosis of the lumen increased. The II-IV stenosis group showed different degrees of calcium salt deposition, and there was a significant difference in the relative calcium salt content in the II-IV stenosis group (P0.05). The early CAS plaque (I-II class stenosis group) was mainly derived from the mononuclear macrophage, while the middle and late CAS plaque (III-IV stricture) was the osteoblast phenotype. The cells were mainly derived from vascular smooth muscle cells (vascular smooth muscle cells, VSMCs).IL-6, and the expression of BGP, OPN and RUNX2 increased with the increase of the stenosis of the lumen. IL-6, BGP and RUNX2 in the stricture group were all more significant than those in the normal group. The expression of protein kinase A (Protein kinase A, PKA) and cyclic adenylate reaction element binding protein (Cyclic adenosine monophosphate-response element binding protein, CREB) had a statistically significant linear correlation with the expression of bone associated protein (0.7). 90,0.986,0.919, P0.01) conclusion: the transformation of the osteoblast to the osteoblast and the expression of bone related protein in the coronary artery VSMCs under the action of the inflammatory factor mediated C AMP-PKA pathway eventually lead to calcium salt deposition in the CAS plaque.

【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：D919

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