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目的:探讨mTOR抑制剂对幼鼠痫性发作后早期炎性因子的影响,为预防慢性癫痫形成寻找新的途径。方法:侧脑室注射海人藻酸(KA)诱导幼鼠(P10d)痫性发作(SE),mTOR抑制剂雷帕霉素(RAP)在SE发作后4h腹腔注射给药进行干预1周。分为KA组,KA+RAP组及生理盐水对照组(NS组)。观察慢性期自发性癫痫(SRS)发生率在各组的差异。痫性发作1周后实时定量RT-PCR检测炎性因子白细胞介素1-β(IL-1β)、转移生长因子-1(TGF-1)及环氧合酶-2(COX-2)在各组的表达差异。SE发作后2周Western blotting检测上述3种炎性因子蛋白表达水平在各组的差异。结果:在KA组,20只幼鼠中有14只观察到SRS发作,SRS发生率为70%,而在KA+RAP组中,21只幼鼠中有10只观察到SRS发生,发生率为47.6%,RAP干预明显降低慢性期SRS的发生率(P<0.05)。SE发作后1周IL-1β、TGF-1和COX-2基因表达水平在KA组表达明显增高,KA+RAP干预组较KA组减低,但较NS组表达增高。SE发作后2周IL-1β、TGF-1和COX-2基因表达水平在KA组表达明显增高,KA+RAP干预组较KA组减低,但较NS组表达增高。三种炎性因子表达水平在三组呈现相似变化趋势。结论:mTOR抑制剂能减少慢性期SRS的发生,抑制痫性发作后早期炎性因子IL-1β、TGF-1和COX-2基因和蛋白水平的表达。可能为预防慢性癫痫的形成提供新的思路和途径。
Objective: To investigate the effect of mTOR inhibitor on the early inflammatory factors after the onset of seizures in young rats, and to find a new way to prevent the formation of chronic epilepsy. Methods: The seizures were induced by intracerebroventricular injection of kainic acid (KA) in rats (P10d), and the mTOR inhibitor rapamycin (RAP) was injected intraperitoneally at 4h after SE onset for one week. Divided into KA group, KA + RAP group and saline control group (NS group). To observe the incidence of chronic spontaneous epilepsy (SRS) in each group differences. One week after the epileptic seizure, real-time quantitative RT-PCR was used to detect the expression of IL-1β, TGF-1 and COX-2 Differences in expression of each group. Two weeks after the onset of SE, Western blotting was used to detect the difference of the expression levels of the above three inflammatory factors in each group. RESULTS: In the KA group, 14 out of 20 pups were observed to have an SRS episode of 70%, whereas in the KA + RAP group, 10 out of 21 pups were observed for SRS with a rate of 47.6%. RAP intervention significantly reduced the incidence of chronic SRS (P <0.05). The expression of IL-1β, TGF-β1 and COX-2 gene in KA group was significantly higher than that in KA group, but higher than that in NS group. The expression of IL-1β, TGF-β1 and COX-2 mRNA in KA group were significantly increased 2 weeks after SE onset, but decreased in KA + RAP intervention group compared with KA group, but higher than that in NS group. Three inflammatory cytokines expression levels in the three groups showed a similar trend. CONCLUSION: mTOR inhibitors can reduce the occurrence of chronic SRS and inhibit the expression of the early inflammatory cytokines IL-1β, TGF-1 and COX-2 after epileptic seizure. It may provide new ideas and ways to prevent the formation of chronic epilepsy.