海马内注射内皮素-1导致大鼠痫性发作和海马硬化的初步研究

Intrahippocampal injection of endothelin-1 induces seizures and hippocampal sclerosis in mature rats.

目的观察大鼠海马内注射内皮素(endothelin,ET)-1是否导致大鼠痫性发作和海马硬化。方法立体定位在成年大鼠海马CA3区内分别注射1μL ET-1(200 pmol,15只)、海人酸(kainate,KA5 pmol,15只)或磷酸盐缓冲液(PBS,0.01 mol,8只),观察大鼠行为学、脑电及对侧海马病理学改变。结果海马注射PBS后大鼠未见痫性发作,脑电图呈10～15 Hz、150～200μV基本节律。注射ET-1或KA2 h内大鼠出现不同程度的痫性发作和脑电图异常改变(尖波或尖慢波),KA组3～5级发作率高于ET-1组(86.67%vs 16.67%,P<0.05)。部分ET-1和KA组大鼠在给药后2～3周可见癫痫样发作行为学改变。与PBS组比较,ET-1和KA组给药后48 h对侧海马各区Nissl染色细胞数明显减少,GFAP表达增强(P<0.05);给药后30 d,对侧CA3区和门齿区苔藓纤维出芽评分高于PBS组(P<0.05)。结论海马注射ET-1可以导致大鼠癫痫样行为改变和海马硬化。

Objective To investigate whether intrahippocampal injection of endothelin （ET）-1 can induce epileptic seizures and hippocampal sclerosis in mature rats. Methods ET-1 （200 pmol, 15 rats）, kainate （KA, 5 pmol, 15 rats） or PBS （0.01 mol, 8 rats） was injected into the right dorsal hippocampus of Sprague-Dawley male rats in injection volume of 1 uL for each compound, respectively. All rats were then monitored for 2 h with a Nissl, glial fibrillary acidic protein （GFAP） and Nero-Timm staining was performed at 48 h and 30 d after the injection respectively. Results Animals receiving PBS did not have seizure and their electroencephalographic activities were 10 - 15 Hz, 150 - 200 μV. Both ET-1 and KA treated rats demonstrated different kinds of seizures accompanied with electrographic seizure activities （slow, or sharp-slow waves）. The percentage of grade 3 - 5 seizure rate was significant higher in KA group than in ET-1 group （86. 67% vs 16. 67% ,P 〈0. 05）. Seizures could be observed in some ET and KA treated rats even 2 - 3 weeks after the injection. Compared with PBS treated controls, KA and ET-1 treated rats exhibited less Nissl stained cells, more GFAP staining cells, and higher MFS score at the contralateral hippocampus following injection （P 〈 0. 05, respectively）. Conclusions Intrahippocampal injection of ET-1 can induce epileptic seizure activities and hippocampal sclerosis in rats.