CAJ | 학술논문

目的观察杏仁核点燃癫痫大鼠海马区P-糖蛋白(P-gp)表达及苔藓纤维出芽(MFS)的动态变化. 方法 90只大鼠采用随机数字表法分为假手术对照组(10只)、癫痫组(40只)和治疗组(40只),假手术对照组只安装电极,不予刺激；癫痫组和治疗组制作杏仁核点燃模型,治疗组加用左乙拉西坦灌胃治疗[100 mg/(kg·d),2次/d)].采用Timm银染组织化学方法观察海马区MFS,免疫组化法检测P-gp的表达. 结果 (1)成功制造癫痫模型后,在海马CA3区透明层出现异常MFS,其中S1亚组大鼠MFS评分最低,与假手术对照组比较差异无统计学意义(P＞0.05);S2亚组大鼠评分开始增高,S4亚组大鼠明显增高,S8亚组大鼠达到高峰,与假手术对照组比较差异均有统计学意义(P＜0.05).而治疗组大鼠MFS评分各时间点与假手术对照组比较差异均无统计学意义(P＞0.05).(2)癫痫发作后癫痫组大鼠P-gp表达量呈现出逐渐降低的趋势,S1、S2、S4亚组与假手术对照组差异有统计学意义(P＜0.05)；S8亚组接近正常水平,与假手术对照组比较差异无统计学意义(P＞0.05).治疗组大鼠除Y1亚组外,余各亚组P-gp表达量与假手术对照组比较差异均无统计学意义(P＞0.0S). 结论 MFS是慢性癫痫形成的重要机制,P-gp是癫痫发生的产物,是癫痫药物耐药的主要原因.
목적 관찰행인핵점연전간대서해마구P-당단백(P-gp)표체급태선섬유출아(MFS)적동태변화. 방법 90지대서채용수궤수자표법분위가수술대조조(10지)、전간조(40지)화치료조(40지),가수술대조조지안장전겁,불여자격；전간조화치료조제작행인핵점연모형,치료조가용좌을랍서탄관위치료[100 mg/(kg·d),2차/d)].채용Timm은염조직화학방법관찰해마구MFS,면역조화법검측P-gp적표체. 결과 (1)성공제조전간모형후,재해마CA3구투명층출현이상MFS,기중S1아조대서MFS평분최저,여가수술대조조비교차이무통계학의의(P＞0.05);S2아조대서평분개시증고,S4아조대서명현증고,S8아조대서체도고봉,여가수술대조조비교차이균유통계학의의(P＜0.05).이치료조대서MFS평분각시간점여가수술대조조비교차이균무통계학의의(P＞0.05).(2)전간발작후전간조대서P-gp표체량정현출축점강저적추세,S1、S2、S4아조여가수술대조조차이유통계학의의(P＜0.05)；S8아조접근정상수평,여가수술대조조비교차이무통계학의의(P＞0.05).치료조대서제Y1아조외,여각아조P-gp표체량여가수술대조조비교차이균무통계학의의(P＞0.0S). 결론 MFS시만성전간형성적중요궤제,P-gp시전간발생적산물,시전간약물내약적주요원인.
Objective To explore the relationship between plasticity ofhippocampus neuronal morphology and pathogenesis of epilepsy by observing the changes of mossy fiber sprouting (MFS) and P-glycoprotein (P-gp) expression in the hippoeampus of rat models of amygdala-kindling epilepsy.Methods Ninety male Wistar rats were randomly divided into epilepsy model group (n=40),drug treatment group (n=40) and sham-operated group (n=10).Models of chronic epilepsy were established by stimulating the amygdale; rats in the drug treatment group were perfused antiepileptic drug levetiracetam into stomach [100 mg/(kg·d),twice daily].At different observation time points (1,2,4 and 8 weeks after the treatment),Timm staining was employed to observe the changes of MFS; immunohistochemical method was used to detect the dynamic changes of P-gp.Results (1) After the success of model making,abnormal MFS levels in the hippocampal CA3 transparent layer were noted; lowest MFS scores were noted in S1 subgroup,which showed no significant difference as compared with those in sham-operated group (P＞0.05); the MFS scores in S2,S4 and S8 subgroups increased gradually with a peak level at 8 weeks after inducement,which showed significant difference as compared with those in sham-operated group (P＜0.05).No significant differences on MFS grading scores were noted in the drug treatment group between each two time points (P＞0.05).(2) The P-gp expression in the epilepsy model group showed significant difference at different time points (P＜0.05); highest expression level was noted at one week after the surgery,and returned to normal at four weeks.However,the P-gp expression showed no significant difference in the drug treatment group between each two time points (P＞0.05),except for 1 week after treatment.Conclusion MFS is the important mechanism of chronic epilepsy,and P-gp is the product of epilepsy,which is the main reason of epilepsy drug resistance.