钙敏感受体对T淋巴细胞的作用研究
发布时间：2018-10-09 17:19
【摘要】：目的：探讨钙敏感受体（Calcium sensing receptor, CaSR）在正常人和冠状动脉粥样硬化性心脏病（CAD，简称冠心病）患者外周血T淋巴细胞上的表达，对细胞因子分泌的影响以及与NF-κB和MAPK信号传导通路的关系。 方法：提取健康人与冠心病患者外周血T淋巴细胞，利用PHA体外诱导，使其活化；Western blot检测CaSR蛋白在T淋巴细胞中的表达，同时检测CaSR激动剂及NF-κB和MAPK信号传导通路阻断剂对T淋巴细胞上相关信号传导通路蛋白的影响；ELISA法检测CaSR活化及NF-κB和MAPK信号传导通路阻断剂对T淋巴细胞分泌细胞因子IL-6和TNF-β的影响。 结果：CaSR蛋白在冠心病患者外周血T淋巴细胞上的表达增加；CaSR激动剂促进CaSR的表达；CaSR活化后信号传导通路相关蛋白P-65和ERK1/2表达增加，，而P-JNK和P-38未见明显改变；NF-κB和MAPK通路阻断剂抑制健康人与冠心病患者外周血T淋巴细胞P65、P-ERK1/2的表达；CaSR活化促进健康人与冠心病患者T淋巴细胞分泌细胞因子IL-6和TNF-β，但是这种作用可以被CaSR的抑制剂NPS2390以及NF-κB和MAPK的通路阻断剂抑制。 结论：CaSR激动剂促进外周血T淋巴细胞CaSR的表达；CaSR活化促进正常人外周血T淋巴细胞细胞因子IL-6和TNF-β的分泌，其促细胞因子分泌的作用与NF-κB和MAPK信号传导通路有关；冠心病患者外周血T淋巴细胞中CaSR表达增加，细胞因子IL-6和TNF-β的分泌增多，并与NF-κB和MAPK信号传导途径有关。
[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.
【学位授予单位】：哈尔滨医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R363
本文编号：2260140
[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.
【学位授予单位】：哈尔滨医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R363
【参考文献】
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1 杨志峰,蔡在龙,毛积芳;NF-κB的结构功能及其与疾病的关系[J];生命的化学;2004年04期
本文编号：2260140
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