急性心肌梗死（AMI）是严重危害人类健康的疾病，活化的淋巴细胞分泌的细胞因子参与其中。钙敏感受体（CaSR）是G蛋白偶联受体，本课题组首次发现心肌组织和健康人外周血T淋巴细胞有CaSR的表达。但是，T淋巴细胞CaSR在AMI中的作用，迄今尚无报道。我们在预实验中已检测到AMI病人外周血T淋巴细胞CaSR表达增加。由此推测"T淋巴细胞CaSR可能通过调节细胞因子的分泌参与AMI的发生和发展"。为证实该假说，本课题拟采用基因沉默等分子生物学技术，观察AMI病人外周血T淋巴细胞CaSR表达增加对细胞因子分泌的影响，并探讨与NF-kB、MAPK、PLC-IP3信号转导通路的关系；同时，缺氧条件下培养乳鼠心肌细胞以模拟AMI，并将心肌细胞与沉默了CaSR的T淋巴细胞共培养，观察心肌细胞的受损伤程度，从而了解急性心肌梗死与T淋巴细胞CaSR的因果关系，为AMI的防治提供新靶点。

Acute myocardial infarction (AMI) is a serious disease harmful to human health , which involved with a variety of cytokines secreted by the activated T lymphocytes.Calcium sensitive receptor (CaSR) is a kind of G protein coupled receptor.Our team first discovered the existence of CaSR in myocardial tissue and peripheral T lymphocytes, but the role of CaSR of T lymphocytes on AMI has not been reported.In the previous study, we have found that CaSR expression in the AMI patients peripheral T lymphocytes increased.So, we hypothesize that" CaSR affects acute myocardial infarction occurrence and development by modulating the cytokine secretion from T lymphocytes".To verify this hypothesis, we will use the gene silencing et al.techniques to observe the effect of the increased CaSR on the cytokine secretion and the relation with the NF-kB，MAPK，PLC-IP3 signal transduction pathways in AMI;at the same time, we will culture neonatal rat cardiomyocytes by hypoxia to imitate AMI and co-cultured with the T lymphocytes with silenced CaSR to observe the degree of cardiomyocardial injury.It will make us clear the relation between AMI and CaSR on T lymphocyte and provide a new target for the prevention and control of AMI.

本课题采用了基因沉默、Westernor、ELisa 等分子生物学技术，观察了AMI病人外周血T淋巴细胞CaSR表达增加对细胞因子分泌的影响，近而探讨了AMI外周血T淋巴细胞与NF-kB、MAPK、PLC-IP3信号转导通路的关系；乳鼠心肌细胞缺氧培养模拟AMI，同时与沉默了CaSR的T淋巴细胞共培养，观察了心肌细胞的受损伤程度。结果显示：急性心肌梗死发病时，淋巴细胞表面CaSR表达量和IL-4、IL-6、IL-1及TNF-α的分泌增加伴有T淋巴细胞凋亡率的升高。再灌注的第一天，此变化达到峰值，随后逐渐下降至恢复正常；此作用可能与NF-κB、MAPK-ERK1/2和MAPK-p38信号转导通路有关。并且发现，外周血T淋巴细胞CaSR可能通过调节细胞因子的分泌影响心肌细胞的损伤。本研究了解了急性心肌梗死与T淋巴细胞CaSR的因果关系，为AMI的防治提供新靶点。