Apelin-13对喹啉酸诱导的小鼠脑损伤的作用

发布时间：2019-05-09 03:45

【摘要】：通过同源克隆,于1993年发现了一个新的G蛋白偶联受体,被命名为APJ。在1998年之前,它是一个孤儿受体,它的内源性配体通过反相药理学方法被筛选出来,称这个配体为apelin。自从APJ受体“脱孤”后,对apelin和APJ受体系统的研究越来越多,已经发现它们在许多神经系统和外周组织中表达。已证明apelin-APJ系统具有多种生理,和病理生理功能,这其中包括引起关注最多的心血管系统,此外,它们还在脂质和葡萄糖代谢,体液平衡,以及免疫调节中发挥作用,但是对于它们的神经保护潜能的关注还是相对太少。我们利用喹啉酸(quinolinic acid, QA)分别对昆明系小鼠的海马区和纹状体区的脑组织产生兴奋性损伤,通过苏木精染色,来检测apelin-13在具有这种损伤的小鼠体内所扮演的角色。我们的研究发现：(1)给小鼠的海马微注射lnmol的QA,在背侧海马的CA1区可以引起细胞减少,细胞皱缩等明显的损伤现象,但是共注射高剂量的apelin-13 (5nmol)并不能对这种损伤有所改善。(2)往小鼠纹状体微注射13nmol的QA,能够产生明显的损伤,通过共注射lnmol的apelin-13,纹状体损伤体积明显降低,而0.3nmol的apelin-13不能对这种损伤产生保护作用。因此,apelin/APJ信号系统有希望作为一个内源的神经元存活的应答机制,并且应该更进一步地研究它的神经保护的机制,期望APJ受体能够成为脑损伤治疗的一个新的靶点。
[Abstract]:By homologous cloning, a new G protein-coupled receptor, named APJ., was discovered in 1993. Before 1998, it was an orphan receptor whose endogenous ligand, known as apelin., was screened by reversed-phase pharmacology. Since the isolation of APJ receptors, apelin and APJ receptor systems have been studied more and more, and they have been found to be expressed in many nervous systems and peripheral tissues. The apelin-APJ system has proven to have a variety of physiological, and pathophysiological functions, including the cardiovascular system, which has attracted the most attention. In addition, they play a role in lipid and glucose metabolism, humoral balance, and immune regulation. But little attention has been paid to their neuroprotective potential. We used quinolinic acid (quinolinic acid, QA) to produce excitatory damage to hippocampus and striatum of Kunming mice respectively. The role of apelin-13 in mice with this damage was detected by hematoxylin staining. Our findings are as follows: (1) the microinjection of lnmol QA, into the hippocampus of mice can induce cell reduction and cell shrinkage in the CA1 region of the dorsal hippocampus. However, co-injection of high dose of apelin-13 (5nmol) could not improve the damage. (2) QA, microinjected into the striatum of mice produced obvious damage, and the volume of apelin-13, striatum injury by co-injection of lnmol decreased significantly. The apelin-13 of 0.3nmol could not protect the damage. Therefore, the apelin/APJ signaling system has the potential as an endogenous neuronal survival response mechanism, and should be further studied its neuroprotective mechanism, we hope that APJ receptor can become a new target for brain injury therapy.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R346

【共引文献】