内质网蛋白29在大鼠脑出血继发性脑损伤中的作用研究

Effect of endoplasmic reticulum protein 29 on cerebral injury secondary to intracerebral hemorrhage in rats

目的观察大鼠脑出血后脑组织中内质网蛋白29（ERp29）的表达变化，进而探讨其在脑出血继发性脑损伤中的作用。方法将60只SD大鼠按随机数字表法分为2组：对照组（10只，不做处理）和实验组（50只，在脑立体定位仪下采用自体血注入尾状核法制备脑出血模型）。实验组再分为术后6h、12h、18h、24h、48h5个时相点，对各个时相点的模型鼠分别采用RT—PCR和Westernblotting方法检测脑组织中ERp29和内质网伴侣蛋白Bip／GRp78mRNA及蛋白的表达。结果在脑出血大鼠模型中．BiP／GRp78mRNA及蛋白表达在术后12h开始升高．并随着时间的推移在术后18h、24h、48h继续逐渐升高．于术后48h达顶峰，与对照组比较差异均有统计学意义（P〈0．05）。ERp29mRNA及蛋白表达在术后6h、12h无明显变化，与对照组比较差异无统计学意义（P〉0．05）；而在术后18h、24h、48hERp29mRNA及蛋白表达明显升高，与对照组比较差异均有统计学意义（P〈0．05）。结论大鼠脑出血后18h时血肿周围脑组织细胞中发生了内质网应激反应，而ERp29在此过程中表达升高，推测其有可能作为一种保护因子并以与BiP／GRp78相互作用形成复合物的形式来抵抗细胞内质网应激反应．进而减轻血肿对周围脑组织造成的损害。

Objective To investigate the expression changes of endoplasmic reticulum protein 29 （ERp29） in the rat brain tissue after cerebral hemorrhage, and explore its role in cerebral injury secondary to intracerebral hemorrhage. Methods Sixty SD rats, weighting （200±20） g, were randomly divided into normal control group （n=10） and cerebral hemorrhage group （n=50）; rat models in the cerebral hemorrhage group were induced by stereotactie injection of autologous blood into the caudate nucleus. RT-PCR and Western blotting were employed to detect the mRNA and protein expressions of ERp29 and endoplasmic reticulum chaperones BIp/GRp78 at 6, 12, 18, 24 and 48 h after the inducement. Results The mRNA and protein expressions of BIp/GRp78 began to increase 12 h after the inducement, and gradually increased with the time prolongation, reaching their peak levels at 48 h after the inducement, which were significantly different as compared with those in the normal control group （P〈0.05）. The mRNA and protein expressions of ERp29 in the cerebral hemorrhage group at 6 and 12 h after the inducement showed no obvious changes as compared with those in the control group （P〉 0.05）, while the mRNA and protein expressions of ERp29 in the cerebral hemorrhage group 18, 24 and 48 h after the inducement were obviously increased as compared with those in the control group （P〈0.05）. Conclusion The endoplasmic reticulum stress response is activated in the surrounding brain tissue of hematoma and the expressions of ERp-29 is up-regulated at this process, which indicates that ERp-29 might play a protective role and interact with Bip/GRp78 to inhibit the process of endoplasmic reticulum stress response so as to decrease the damaged effect of hematoma to the surrounding brain tissue.