Stanojlović Olivera, Hrncić Dragan, Turjacanin Drenka, Zivanović Dragana, Susić Veselinka
Mecicinski fakultet, Institut za fiziologiju, 11000 Beograd.
Med Pregl. 2007 Sep-Oct;60(9-10):436-40. doi: 10.2298/mpns0710436s.
We investigated the potential of delta sleep-inducing peptide (DSIP) and its analogue DSIP-12 (a nonapeptide with alanine in position 2 of DISP molecule substituted by beta-alanine) and tetrapeptide analogue DSIP1-4, to antagonize metaphit(1-1 (3-isothiocyanatophenl)-cvyclohexyl piperidine) induced generalized reflex audiogenic seizures in adult male Wistar albino rats.
Five groups of adult male Wistar rats were intraperitoneally treated with: (1) saline; (2) metaphit: (3) metaphit + DSIP, (4) metaphit + DSIPI-4 and (5) metaphit + DSIP-12. To examine the blocking effects of DSIP and its analogues on fully developed metaphit seizures, in the last three groups they were administered 8h after metaphit injection. The rats were stimulated using an electric bell (1003 dB, 5-8 kHz, 60 s) one hour after metaphit injection and afterwards at hourly intervals during the experiment. For EEG recordings and power spectra three gold-plated screws were implanted into the skull.
In metaphit-treated animals EEGs appeared as polyspikes and spike-wave complexes, while power spectra were increasing. The incidence and severity of netaphit-induced audiogenic seizures reached a peak value at 7-12 h after injection. Both DSIP and DSIP analogues significantly increased power spectra of delta waves and decreased the incidence of seizures, as well as mean seizure grade and tonic component of metaphit-induced convulsions.
Taken together, these results suggest that DSIP and its analogues should be considered as potential antiepileptic agents.
我们研究了δ-睡眠诱导肽(DSIP)及其类似物DSIP-12(一种非肽,DSIP分子第2位的丙氨酸被β-丙氨酸取代)和四肽类似物DSIP1-4拮抗偏端菌素(1-1(3-异硫氰酸苯酯)-环己基哌啶)诱导成年雄性Wistar白化大鼠全身性反射性听源性癫痫发作的潜力。
将五组成年雄性Wistar大鼠进行腹腔注射治疗:(1)生理盐水;(2)偏端菌素;(3)偏端菌素+DSIP;(4)偏端菌素+DSIPI-4;(5)偏端菌素+DSIP-12。为了检测DSIP及其类似物对完全发作的偏端菌素癫痫发作的阻断作用,在后三组中,在注射偏端菌素8小时后给予它们。在注射偏端菌素1小时后,使用电铃(1003分贝,5-8千赫,60秒)刺激大鼠,然后在实验期间每隔1小时刺激一次。为了进行脑电图记录和功率谱分析,将三个镀金螺丝植入颅骨。
在接受偏端菌素治疗的动物中,脑电图表现为多棘波和棘慢复合波,而功率谱增加。偏端菌素诱导的听源性癫痫发作的发生率和严重程度在注射后7-12小时达到峰值。DSIP及其类似物均显著增加了δ波的功率谱,降低了癫痫发作的发生率、平均癫痫发作等级以及偏端菌素诱导惊厥的强直成分。
综上所述,这些结果表明DSIP及其类似物应被视为潜在的抗癫痫药物。