戊四氮点燃大鼠脑内P-糖蛋白和缺氧诱导因子1α的表达及相关性

Expression and correlation between P-glycoprotein and Hypoxia inducible factor-1α in brain of rats following pentylenetetrazol-kindled seizure

目的研究戊四氮点燃大鼠脑内 P-糖蛋白(P-gp)和缺氧诱导因子1α(Hif-1α)的表达变化和表达部位,探讨二者之间的关系。方法反复腹腔注射戊四氮(40 mg/kg)制备大鼠点燃模型或注射 PBS 作对照。点燃后不同时间点处死动物。用免疫组织化学染色方法检测 P-gp 和 Hif-1α的表达变化,用双标免疫酶组织化学染色法确定 P-gp 和 Hif-1α的表达部位。结果对照组的 P-gp 和Hif-1α零星分布在毛细血管内皮细胞,点燃组 P-gp 和 Hif-1α分布在海马和皮质神经元的细胞膜,均以点燃后4 h 的表达最高(P-gp:1.09±0.20;Hif-1α:1.12±0.19,F=2.83,P<0.05),且分布方式相似。结论癫癎反复发作可以诱导脑内神经元表达 P-gp 和 Hif-1α,二者可能具有相关性。

Objective To explore the correlation between P-glyeopretein （P-gp） and hypoxia inducible factor 1α （Hif-1α） by investigating the expression and location of P-gp and Hif let in the brain of rats after pentylenetetrazol-kindled seizures. Methods Pentylenetetrazol kindling model was induced by intraperitoneal injection of pentylenetetrazol （40 mg/kg, twice daily） , and rats with injection of PBS were used as control. The expression and location of P-gp and Hif-1α were examined by immunohistochemistry and double-label immunostaining. Results In the eontrel group, P-gp and Hif-1α were weakly positive in blood vessels and negative in brain parenehyma. In the kindling group, P-gp and Hif-1α were observed in parenehymal neurons in the cortex and hippocampus, which were co-labelled with NeuN, respectively, but without GFAP. Expression of P-gp and Hif-1α increased to a maximal intensity 4 h after kindling （P-gp： 1.09 ±0. 20; Hif-1α： 1.12 ±0. 19, F =2. 83, P 〈0. 05）. Expression and distribution pattern of P-gp and Hif-1α were similar. Conclusions Recurrent seizures induced by pentylenetetrazol-kindling can induce neuronal expression of P-gp and Hif-1α, suggesting that there probably is eorrelativity between them.