脑室注射痛敏素／孤啡肽FQ对局灶性脑缺血大鼠梗死体积和体感诱发电位的影响

Influence of Intracerebroventricular Injection of Nociceptin/Orphanin FQ on Cerelral Infarction Volume and Somatosensory Evoked Potential in Focal Cerelral Ischemia in Rats

目的：观察痛敏素／孤啡肽（N／OFQ）对脑缺血大鼠梗死体积和体感诱发电位（SEP）的影响。方法：41只SD大鼠随机分为大脑中动脉闭塞（MCAO）假手术组（n=5）、缺血组（n=8）、N／OFQ 10μg组（n=7）、N／OFQ 1μg组（n=7）、N／OFQ 0.1μg组（n=7）和人工脑脊液（ACSF）组（n=7）。采用腔内线栓法制作大鼠MCAO模型，MCAO后2h再灌注。N／OFQ 10μg组、N／OFQ 1μg组、N／OFQ 0.1μg组和ACSF组分别在MCAO后1h脑室内注射N／OFQ 10μg、N／OFQ 1μg、N／OFQ 0.1μg和体积相同ACSF。检测再灌注24h后脑梗死体积体，并记录SEP。结果：假手术组SEP P1波幅降低，P1峰潜时间无显著变化。N／OFQ 0．1μg组SEP波幅、P1峰潜时间和脑梗死体积与ACSF组无显著差异。N／OFQ 1μg组和N／OFQ 10μg组SEP波幅较ACSF组进一步降低，但P1峰潜时间无显著变化。ACSF组SEP波幅在再灌注后1h基本恢复至缺血前水平，N／OFQ1μg组恢复减慢，N／OFQ10μg组直到再灌注后3h仍未恢复。N／OFQ剂量与SEP反应呈量效关系，剂量越大，SEP抑制越显著，恢复越慢。再灌注24h时，假手术组、ACSF组、N／OFQ 0．1μg组、N／OFQ 1μg组和N／OFQ 10μg组脑梗死体积分另1为0mm^3、（24．180±4．088）mm^3、（23．090±4．523）mm^3、（35．304±6．824）mm^3和（40．806±6．716）mm^3，N／OFQ 0．1μg组与ACSF组无显著差异，N／OFQ 1μg组和N／OFQ 10μg组与ACSF组均有显著差异（P均〈0．01）。结论：脑缺血早期侧脑室注射N／OFQ可使SEP波幅降低、恢复时间延长，梗死体积增大，表明其可加重缺血性脑损伤。

Objective： To observe the influence of nociceptin/orphanin FQ （N/OFQ） on cerebral infarction volume and somatosensory evoked potential （SEP） in focal cerebral ischemia in rats. Methods： Forty one SD rats were randomly allocated into middle artery occlusion （MCAO） sham-operation （n =5）, ischemic （n =8）, N/OFQ 10 μg （n =7）, N/OFQ 1 μg （n =7）, N/OFQ 0. 1 μg （n =7）, and artificial cerebrospinal fluid （ACSF） （n =7） groups. A model of middle cerebral artery occlusion （MCAO） in rats was induced using the intraluminal suture method. Reperfusion was performed 2 hours after MCAO. One hour after MCAO, N/OFQ 10 μg,N/OFQ 1μg, N/OFQ 0.1μg, and the same volume of ACSF were injected intraventricularly in the N/OFQ 10 μg, N/OFQ 1 μg, N/OFQ 0. 1 μg, and ACSF groups, respectively. The cerebral infarction volume was detected 24 hours after reperfusion, and SEP was recorded. Resets： The amplitude of SEP P 1 decreased in the sham-operation group. There was no significant change in P1 peak latencies. There were no significant differences between the N/OFQ 0.1 μg group and the ACSF group in SEP amplitudes, P1 peak lantecies and cerebral infarction volume. As compared with the ACSF group, the SEP amplitudes were further decreased in the N/OFQ 1 μg and N/OFQ 10μg groups, but there were no significant change in P1 peak lantecies. One hour after reperfnsion, the SEP amplitude in the ACSF group almost returned to the level of preischemia, the recovery slowed down in the N/OFQ 1 μg group, and it still did not recovered 3 hours after reperfusion in the N/OFQ 10 μg group. The dose of N/OFQ and SEP response showed dose-effect relationship. The higher the dose, the deeper the SEP depression and the slower the recovery. At 24 hours after reperfusion, the cerebral infarction volumes in the shamoperation, ACSF, N/OFQ 0. 1μg, N/OFQ 1 μg, and N/OFQ 10 μg groups were 0 mm^3, 24. 180 ± 4. 088 mm^3, 23. 090 ± 4. 523 mm^3, 35. 304 ± 6. 824 mm^3, and 40. 806 ± 6.716 mm^3, respectively. There was no significant difference between N/OFQ 0. 1 and ACSF groups. There were significant differences between N/OFQ 1μg and 10 μg groups and ACSF group （all P 〈0.01 ）. Conclusions： Intracerebroventricular injection of N/OFQ in the early stage of cerebral ischemia decreases the SEP amplitude, prolongs the time of recovery, and increases cerebral infarction volume, which shows that it may aggravate cerebral ischemic, injury.