NGF对局灶性脑缺血再灌注后大鼠海马CHOP mRNA及蛋白表达的影响

探讨NGF对局灶性脑缺血再灌注后大鼠海马神经元CHOPmRNA及蛋白表达的影响。用线栓法制作大鼠右侧大脑中动脉阻塞再灌注模型(MCAO),应用原位杂交方法检测CHOPmRNA的表达;应用免疫组织化学SABC法检测CHOP蛋白表达;应用显微图像分析系统进行分析。结果显示:假手术组大鼠海马CHOPmRNA及蛋白表达极少;缺血组较假手术组CHOP表达mRNA和蛋白均显著增加(P<0.01),缺血再灌注3h后CHOPmRNA表达明显增加,24h达高峰,48h开始显著下降,72h接近对照组水平,CHOP蛋白在缺血再灌注12h时明显表达增高,24h达到高峰,72h显著下降,但仍高于对照组水平(P<0.01);在缺血再灌注12、24、48h,NGF组CHOPmRNA及蛋白表达明显低于缺血组(P<0.01)。本研究表明,外源性NGF能显著抑制局灶性脑缺血再灌注后CHOPmRNA及蛋白表达,提示NGF可能对脑缺血再灌注损伤后的海马神经元有保护作用。

THE EFFECT OF NERVE GROWTH FACTOR ON THE EXPRESSION OF CHOP mRNA AND PROTEIN IN HIPPOCAMPUS OF RATS WITH FOCAL CEREBRAL ISCHEMIA/REPERFUSION

The study was to investigate the effect of nerve growth factor on the expression of CHOP mRNA and protein in hippocampus of rats with focal cerebral ischemia/reperfusion (I/R). A rat right middle cerebral artery occlusion/reperfusion (MCAO) model was made by using intraluminafilament. In situ hybridization, immunohistochemistry and computer-assisted image analysis system were performed to observe the expressions of CHOP mRNA and its protein in the hippocampus of rats with I/R. The results showed that the expressions of CHOP mRNA and protein were markedly higher in I/R group compared with sham group(P<0.01). CHOP mRNA was expressed and obviously increased at 3 h,reached peak at 24 h,clearly decreased at 48 h,and approached to a control level at 72 h in I/R group after I/R.CHOP protein was largely expressed at 12 h,reached a maximum at 24 h, markedly decreased at 72 h in I/R group after I/R(P<0.01), but still higher than that in sham group. The expressions of CHOP mRNA and its protein were markedly lower in NGF group than that in I/R group at 12, 24, 48 h after I/R (P<0.01). The results indicate that CHOP mRNA and its protein were induced in the hippocampus of rats after I/R , the downregulations of NGF on the expressions of CHOP mRNA and its protein indicate that NGF has protective effect on the ischemic neurons of hippocampus after focal cerebral ischemia/reperfusion.