雷帕霉素对未成年癫痫模型大鼠的毒性作用

Toxic effect of rapamycin in a young rat model of pentylenetetrazole-induced Kindling epilepsy

目的利用戊四氮(pentylenetetrazol,PTZ)慢性点燃Sprague Dawley大鼠(SD大鼠)模型观察在点燃初期腹腔注射雷帕霉素(rapamycin,RAPA)能否抑制癫痫发生以及雷帕霉素在治疗中的安全性。方法将6~8周龄SD雄性大鼠随机分为雷帕霉素干预组PTZ+RAPA及其对照组PTZ+NS(normal saline)及NS组,观察1周(w)、2周(w)、4周(w)、6周(w)共4个时间点,每亚组12只,观察实验动物体质量的变化、死亡率及癫痫发作情况。结果各组实验大鼠的死亡率:PTZ+RAPA组为22.9%,PTZ+NS组为10.4%,NS组为0%。PTZ+RAPA组与PTZ+NS组各个相对应的时间点(1 w,2 w,4 w,6 w)体质量差均有统计学差异(P<0.001)。6周时PTZ+RAPA组的点燃率为66.7%,PTZ+NS组的点燃率为58.3%,二者无统计学差异(P>0.05)。PTZ+RAPA组与PTZ+NS组相对应时间点(1 w,2 w,4 w,6 w)发作分值的两两比较差异无统计学意义(P>0.05)。结论雷帕霉素未能减少或抑制未成年大鼠的癫痫发作,但能明显降低未成年SD大鼠的体质量,可能有一定的毒副作用。

Objective To examine the effectiveness and safty of intraperitoneal injection of rapamycin on epileptogenesis in a rat model of pentylenetetrazole-induced kindling epilepsy. Method The Sprague Dawley rats at 6-8 weeks old were randomly divided into group PTZ＋RAPA and group PTZ＋NS. The body weight, mortality and seizures were recorded at 1, 4 and 6 weeks after treatment. Mossy fiber sprouting in the hippocampal CA3 area and DG area was examined by Tim staining. Results 1.The rats mortality was 22.9% in PTZ＋RAPA and 10.4% in PTZ＋NS. Weight alteration was statistically significant between PTZ＋RAPA and PTZ＋NS at the corresponding time points （P〈 0.001）; 3. The kindling rate was 66.7% in PTZ＋RAPA and 58.3% in PTZ＋NS at 6 weeks and the difference was statistical significant between these two groups （P〉0.05）. There was no statistical significance in the seizure scores be-tween PTZ＋RAPA and PTZ＋NS （P〉 0.05）. 4.The scores of mossy fiber sprouting in hippocampal CA3 and DG areas was higher in PTZ＋NS than in PTZ＋RAPA （P〈0.05）. Conclusion Rapamycin cannot reduce or curb epileptic seizures in young rats. It can obviously reduce the weight of the young SD rats which may be associated with its side effects.