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目的研究脂多糖海马内注射激活胶质细胞免疫反应引起大鼠痫性发作及海马硬化的作用机制。方法随机将36只成年雄性Wistar大鼠分为脂多糖组(LPS组)、海人酸组(KA组)、生理盐水组(NS组)。立体定位在大鼠CA3区分别注射脂多糖5μg/μL、生理盐水、海人酸0.4μg/μL各1.5μL,记录大鼠的行为学、脑电图;行海马区HE染色观察神经元形态;采用免疫组化法检测胶质纤维酸性蛋白(GFAP)和神经元型一氧化氮合酶(nNOS)的表达。结果海马内注射NS后大鼠未见痫性发作,脑电图呈基本节律。注射LPS或KA后2 h内大鼠出现不同程度的痫性发作和脑电图异常改变(尖波或棘波),KA组发作等级高于LPS组,部分LPS和KA组大鼠在给药后3～4周仍可见痫性发作。与NS组比较,LPS和KA组给药后急性期海马各区星形胶质细胞活化,神经元nNOS活性增高,慢性期星形胶质细胞增生,神经元数量减少,呈海马硬化表现。结论海马内注射脂多糖可激活胶质细胞的固有免疫反应,并导致大鼠痫性发作和海马硬化。
Objective To investigate the mechanism of intra-hippocampal injection of lipopolysaccharide (LPS) in activation of glial cell-mediated immune response in rats with epileptic seizures and hippocampal sclerosis. Methods Thirty-six adult male Wistar rats were randomly divided into LPS group, KA group and NS group. Stereotactic injection of lipopolysaccharide 5μg / μL, normal saline, 1.5μg / μL L-arginine 1.5μl respectively in CA3 area of rats, behavioral and electroencephalogram of rats were recorded; HE staining of hippocampus was used to observe neuronal morphology; The expression of glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) were detected by immunohistochemistry. Results There was no seizure in rats after NS injection of hippocampus, and electroencephalogram showed basic rhythm. Within 2 h after injection of LPS or KA, the rats experienced different degrees of epileptic seizures and abnormal EEG changes (spike wave or spike wave), the severity of attack in KA group was higher than that in LPS group, and some rats in LPS and KA group 3 to 4 weeks after the epileptic seizures are still visible. Compared with the NS group, the astrocytes in the hippocampus and the nNOS activity in the hippocampus were increased in the LPS and KA groups, and the numbers of neurons in the hippocampus were decreased in the chronic phase, showing hippocampal sclerosis. Conclusion Intra-hippocampal injection of lipopolysaccharide can activate innate immune responses of glia cells and cause seizures and hippocampal sclerosis in rats.