Guo Wen-Ping, Wang Jie, Li Rui-Xi, Peng Yu-Wen
Department of Anatomy, Shanghai Medical College, Fudan University, 138 YiXue Yuan Road, Shanghai 200032, PR China.
Brain Res. 2006 May 4;1087(1):180-5. doi: 10.1016/j.brainres.2006.03.007. Epub 2006 Apr 17.
The purpose of this study was to investigate the therapeutic efficacy and mechanism of recombinant human NRG-1 to attenuate ischemia/reperfusion brain injury. NRG-1(3.0 ng/kg) was applied intravascularly 10 min before middle cerebral artery occlusion (MCAO) and then focal cerebral ischemia for 90 min and reperfusion for 24 h. The rats were scored post-reperfusion for neurological deficits and infarct volume in the brain was assessed by 2,3,5-triphenyltetrazolium chloride(TTC). Apoptosis was evaluated by TUNEL staining. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure changes of caspase-3 mRNA. The level of TNF-alpha was determined using enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that recombinant human NRG-1 could reduce cerebral infarct volume by about 71% (P < 0.05) and TUNEL positive cells when given immediately before MCAO, and improved behavior of animals. Furthermore, we also showed that NRG-1 could also decrease the expression of caspase-3 mRNA and production of TNF-alpha protein. These data suggest that pre-administration of NRG-1 attenuates cerebral ischemia and reperfusion injury. This protective effect may be involved in the inhibition of caspase-3 and TNF-alpha.
本研究旨在探讨重组人神经调节蛋白-1（NRG-1）减轻脑缺血/再灌注损伤的治疗效果及机制。在大脑中动脉闭塞（MCAO）前10分钟经血管给予NRG-1（3.0 ng/kg），然后进行局灶性脑缺血90分钟并再灌注24小时。再灌注后对大鼠进行神经功能缺损评分，并用2,3,5-三苯基氯化四氮唑（TTC）评估脑梗死体积。通过TUNEL染色评估细胞凋亡。采用逆转录聚合酶链反应（RT-PCR）检测半胱天冬酶-3（caspase-3）mRNA的变化。使用酶联免疫吸附测定（ELISA）测定肿瘤坏死因子-α（TNF-α）水平。我们的结果表明，在MCAO前立即给予重组人NRG-1可使脑梗死体积减少约71%（P < 0.05），并减少TUNEL阳性细胞，改善动物行为。此外，我们还表明NRG-1还可降低caspase-3 mRNA的表达和TNF-α蛋白的产生。这些数据表明，预先给予NRG-1可减轻脑缺血和再灌注损伤。这种保护作用可能与抑制caspase-3和TNF-α有关。
