CAJ | 학술논문

目的评价糖原合成酶激酶3β(GSK-3β)在大鼠脊髓缺血再灌注损伤中的作用.方法雄性SD大鼠48只,3月龄,体重250～ 300 g,采用随机数字表法,将其分为3组(n=16):假手术组(S组)、脊髓缺血再灌注组(I/R组)和GSK-3β抑制剂氯化锂组(LiCl组).采用夹闭腹主动脉45 min恢复灌注的方法制备大鼠脊髓缺血再灌注损伤模型.I/R组和LiCl组于再灌注前30 min时经尾静脉分别注射生理盐水5 ml和GSK-3β抑制剂氯化锂15 mg/kg.再灌注48 h时处死大鼠,取L4-6脊髓组织,光镜下观察病理学结果,采用TUNEL法测定脊髓前角神经细胞凋亡情况,计算神经细胞凋亡率,采用免疫组化法测定脊髓前角IL-6、IL-8和IL-10的表达水平.结果与S组比较,I/R组和IR+ LiCl组脊髓前角细胞凋亡率升高,IL-6和IL-8的表达上调,IL-10表达下调(P＜0.05);与I/R组比较,LiCl组脊髓前角细胞凋亡率降低,IL-6和IL-8的表达下调,IL-10表达上调(P＜0.05),病理学损伤减轻.结论 GSK-3β激活后可能通过促进炎性因子的合成和释放,参与大鼠脊髓缺血再灌注损伤.
목적 평개당원합성매격매3β(GSK-3β)재대서척수결혈재관주손상중적작용.방법 웅성SD대서48지,3월령,체중250～ 300 g,채용수궤수자표법,장기분위3조(n=16):가수술조(S조)、척수결혈재관주조(I/R조)화GSK-3β억제제록화리조(LiCl조).채용협폐복주동맥45 min회복관주적방법제비대서척수결혈재관주손상모형.I/R조화LiCl조우재관주전30 min시경미정맥분별주사생리염수5 ml화GSK-3β억제제록화리15 mg/kg.재관주48 h시처사대서,취L4-6척수조직,광경하관찰병이학결과,채용TUNEL법측정척수전각신경세포조망정황,계산신경세포조망솔,채용면역조화법측정척수전각IL-6、IL-8화IL-10적표체수평.결과 여S조비교,I/R조화IR+ LiCl조척수전각세포조망솔승고,IL-6화IL-8적표체상조,IL-10표체하조(P＜0.05);여I/R조비교,LiCl조척수전각세포조망솔강저,IL-6화IL-8적표체하조,IL-10표체상조(P＜0.05),병이학손상감경.결론 GSK-3β격활후가능통과촉진염성인자적합성화석방,삼여대서척수결혈재관주손상.
Objective To evaluate the role of glycogen synthase kinase-3 beta (GSK-3β) in spinal cord ischemia/reperfusion (I/R) injury in rats.Methods Forty-eight male Sprague-Dawley rats,aged 3 months,weighing 250-300 g,were randomly divided into 3 groups (n =16 each) using a random number table:sham operation group (group S),group I/R and I/R+ GSK-3β inhibitor LiCl group (group LiCl).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 300 mg/kg.Spinal cord ischemia was induced by 45 min occlusion of the abdominal aorta followed by reperfusion.In I/R and LiCl groups,normal saline 5 ml and LiCl 15 mg/kg were injected,respectively,via the caudal vein at 30 min before ischemia.The animals were sacrificed at 48 h of reperfusion and the lumbar segment (L4-6) of spinal cords was removed for microscopic examination and for determination of neuronal apoptosis in the anterior horn of the spinal cord (by TUNEL),and the expression of interleukin-6 (IL-6),IL-8 and IL-10 was detected (by immunohistochemistry).The apoptosis rate was calculated.Results Compared with group S,the apoptosis rate was significantly increased,IL-6 and IL-8 expression was upregulated,and IL-10 expression was down-regulated in I/R and LiCl groups.Compared with group I/R,the apoptosis rate was significantly decreased,IL-6 and IL-8 expression was down-regulated,IL-10 expression was up regulated,and the pathological damage was attenuated in LiCl group.Conclusion Activated GSK-3β is involved in the development of spinal cord I/R injury possibly by promoting synthesis and release of inflammatory factors in rats.