CAJ | 학술논문

目的：观察海马电刺激对海人酸点燃大鼠海马突触外GABAA 受体α5亚基的影响，探讨海马电刺激最佳治疗参数及其对癫痫的可能治疗机制。方法雄性SD大鼠成功致痫模型32只，按随机数字表法分为癫痫组、假手术组、低频电刺激（ LFS）治疗组和高频电刺激（ HFS）治疗组，每组8只，正常对照组大鼠8只。通过行为学、实时荧光定量聚合酶链式反应和免疫印迹检测各组α5亚基相关mRNA和蛋白在海马中的表达。结果（1）海人酸点燃大鼠制模成功率为65％。治疗期间LFS治疗组、HFS治疗组分别与假手术组和癫痫组比较癫痫发作次数明显减少（ P＜0.01），但LFS治疗组与HFS治疗组比较癫痫发作次数差异无统计学意义（P＞0.05），假手术组与癫痫组比较癫痫发作次数差异无统计学意义（P＞0.05）。（2）癫痫组、假手术组、LFS治疗组、HFS治疗组与正常对照组α5亚基蛋白表达分别为0.22±0.08、0.26±0.08、0.75±0.09、0.74±0.09、0.88±0.09，均P＜0.01，组间多重比较：LFS治疗组、HFS治疗组分别与假手术组、癫痫组之间α5亚基相关蛋白比较差异有统计学意义（ P＜0.01），其中， LFS治疗组与HFS治疗组比较P＞0.05，假手术组与癫痫组比较P＞0.05。 LFS治疗组、HFS治疗组分别与正常对照组比较差异有统计学意义（ P＜0.01）。结论海马电刺激可有效抑制癫痫发作，低频电刺激与高频电刺激同样有效，低频电刺激效益更高；突触外α5亚基在海马电刺激抑制癫痫发作中起到重要作用。
목적：관찰해마전자격대해인산점연대서해마돌촉외GABAA 수체α5아기적영향，탐토해마전자격최가치료삼수급기대전간적가능치료궤제。방법웅성SD대서성공치간모형32지，안수궤수자표법분위전간조、가수술조、저빈전자격（ LFS）치료조화고빈전자격（ HFS）치료조，매조8지，정상대조조대서8지。통과행위학、실시형광정량취합매련식반응화면역인적검측각조α5아기상관mRNA화단백재해마중적표체。결과（1）해인산점연대서제모성공솔위65％。치료기간LFS치료조、HFS치료조분별여가수술조화전간조비교전간발작차수명현감소（ P＜0.01），단LFS치료조여HFS치료조비교전간발작차수차이무통계학의의（P＞0.05），가수술조여전간조비교전간발작차수차이무통계학의의（P＞0.05）。（2）전간조、가수술조、LFS치료조、HFS치료조여정상대조조α5아기단백표체분별위0.22±0.08、0.26±0.08、0.75±0.09、0.74±0.09、0.88±0.09，균P＜0.01，조간다중비교：LFS치료조、HFS치료조분별여가수술조、전간조지간α5아기상관단백비교차이유통계학의의（ P＜0.01），기중， LFS치료조여HFS치료조비교P＞0.05，가수술조여전간조비교P＞0.05。 LFS치료조、HFS치료조분별여정상대조조비교차이유통계학의의（ P＜0.01）。결론해마전자격가유효억제전간발작，저빈전자격여고빈전자격동양유효，저빈전자격효익경고；돌촉외α5아기재해마전자격억제전간발작중기도중요작용。
Objective To observe the effects of electrical hippocampal stimulation of α5 subunit of extrasynaptic GABA A receptor in kainic acid-induced epileptic rats , explore the optimal therapeutic parameters and elucidate the possible mechanism of electrical stimulation for hippocampal epilepsy .Methods A total of 40 healthy male Sprague Dawley ( SD) rats were randomly divided into 5 groups of epilepsy, sham operation, low-frequency stimulation (LFS), high-frequency stimulation (HFS) and normal control ( n =8 each ).The expression of α5 subunit of extrasynaptic GABA A receptor as well as the association with the curative effects of LFS were evaluated by behavioristics , real-time fluorogenic quantitative polymerase chain reaction ( PCR) and Western blot.Results The kainic acid kindling rats had class Ⅴattack with a modeling success rate of 67%.After treatment, as compared with sham operation and epilepsy groups , the number of seizures decreased significantly in LFS and HFS treatment groups ( P <0.01).But LFS and HFS treatment groups were compared , the number of seizures has no statistical significance ( P>0.05).When sham operation and epilepsy groups were compared , the number of seizures was not statistically significant ( P>0.05 ).The paired inter-group comparisons showed that LFS and HFS treatment groups and sham operation and epilepsy groups had significant differences in α5 subunit mRNA and protein (P<0.01).No statistical significance existed between LFS and HFS treatment groups (P>0.05) or sham operation and HFS treatment groups ( P>0.05 ).As compared with normal control group , LFS treatment and HFS groups had significant difference ( P <0.01 ).Conclusion Electrical hippocampal stimulation can effectively inhibit seizures.Both LFS and HFS are equally effective , but the former offers greater benefits.And an inhibition of extrasynaptic α5 subunit plays an important role in seizure during hippocampal stimulation.