【摘要】：目的：探討鈣敏感受體（Calcium sensing receptor, CaSR）在正常人和冠狀動脈粥樣硬化性心臟�。–AD，簡稱冠心�。┗颊咄庵苎猅淋巴細(xì)胞上的表達(dá)，對細(xì)胞因子分泌的影響以及與NF-κB和MAPK信號傳導(dǎo)通路的關(guān)系。 方法：提取健康人與冠心病患者外周血T淋巴細(xì)胞，利用PHA體外誘導(dǎo)，使其活化；Western blot檢測CaSR蛋白在T淋巴細(xì)胞中的表達(dá)，同時檢測CaSR激動劑及NF-κB和MAPK信號傳導(dǎo)通路阻斷劑對T淋巴細(xì)胞上相關(guān)信號傳導(dǎo)通路蛋白的影響；ELISA法檢測CaSR活化及NF-κB和MAPK信號傳導(dǎo)通路阻斷劑對T淋巴細(xì)胞分泌細(xì)胞因子IL-6和TNF-β的影響。 結(jié)果：CaSR蛋白在冠心病患者外周血T淋巴細(xì)胞上的表達(dá)增加；CaSR激動劑促進CaSR的表達(dá)；CaSR活化后信號傳導(dǎo)通路相關(guān)蛋白P-65和ERK1/2表達(dá)增加，，而P-JNK和P-38未見明顯改變；NF-κB和MAPK通路阻斷劑抑制健康人與冠心病患者外周血T淋巴細(xì)胞P65、P-ERK1/2的表達(dá)；CaSR活化促進健康人與冠心病患者T淋巴細(xì)胞分泌細(xì)胞因子IL-6和TNF-β，但是這種作用可以被CaSR的抑制劑NPS2390以及NF-κB和MAPK的通路阻斷劑抑制。 結(jié)論：CaSR激動劑促進外周血T淋巴細(xì)胞CaSR的表達(dá)；CaSR活化促進正常人外周血T淋巴細(xì)胞細(xì)胞因子IL-6和TNF-β的分泌，其促細(xì)胞因子分泌的作用與NF-κB和MAPK信號傳導(dǎo)通路有關(guān)；冠心病患者外周血T淋巴細(xì)胞中CaSR表達(dá)增加，細(xì)胞因子IL-6和TNF-β的分泌增多，并與NF-κB和MAPK信號傳導(dǎo)途徑有關(guān)。
[Abstract]:Objective: to investigate the expression of calcium sensitive receptor (Calcium sensing receptor, CaSR) on peripheral blood T lymphocytes in normal subjects and patients with coronary atherosclerotic heart disease (CAD,). The effect on cytokine secretion and its relationship with NF- 魏 B and MAPK signal transduction pathway. Methods: peripheral blood T lymphocytes were extracted from healthy subjects and patients with coronary heart disease (CHD) and induced by PHA in vitro. The expression of CaSR protein in T lymphocytes was detected by PHA activation Western blot. The effects of CaSR agonists, NF- 魏 B and MAPK signaling pathway blockers on the related signal transduction pathway proteins in T lymphocytes were also detected. The activation of CaSR and the effects of NF- 魏 B and MAPK signal transduction pathway blockers on the secretion of IL-6 and TNF- 尾 by T lymphocytes were detected by ELISA. Results the expression of CaSR protein in peripheral blood T lymphocytes of patients with coronary heart disease was increased. CaSR agonists promoted the expression of CaSR. The expression of P-65 and ERK1/2 related to signal transduction pathway was increased after CaSR activation, but P-JNK and P-38 did not change significantly. NF- 魏 B and MAPK pathway blockers inhibited the expression of P65 P-ERK1 / 2 in peripheral blood T lymphocytes of healthy subjects and patients with coronary heart disease. The activation of CaSR can promote the secretion of cytokines IL-6 and TNF- 尾 by T lymphocytes in healthy people and patients with coronary heart disease, but this effect can be inhibited by NPS2390, an inhibitor of CaSR, and a pathway blocker of NF- 魏 B and MAPK. ConclusionCaSR agonists can promote the expression of CaSR in peripheral blood T lymphocytes. CaSR activation can promote the secretion of IL-6 and TNF- 尾 of T lymphocytes in normal human peripheral blood, which is related to NF- 魏 B and MAPK signal transduction pathway. The expression of CaSR and the secretion of cytokines IL-6 and TNF- 尾 in peripheral blood T lymphocytes were increased in patients with coronary heart disease, which were related to NF- 魏 B and MAPK signal transduction pathway.
【學(xué)位授予單位】：哈爾濱醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R363

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1 楊志峰,蔡在龍,毛積芳;NF-κB的結(jié)構(gòu)功能及其與疾病的關(guān)系[J];生命的化學(xué);2004年04期

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