CAJ | 학술논문

目的评价低氧诱导因子-1α(HIF-1α)基因修饰骨髓间充质干细胞(BMSCs)移植治疗大鼠脊髓缺血再灌注损伤的效果.方法成年健康雄性SD大鼠135只,2月龄,体重200 ～ 300 g,采用随机数字表法,将其分为4组:假手术组(S组,n =20)、缺血再灌注组(I/R组,n=20)、BMSCs组(n=20)和HIF-1α基因修饰BMSCs组(HIF-1α-BMSCs组,n=75).采用阻断腹主动脉45 min行再灌注的方法制备大鼠脊髓缺血再灌注损伤模型,于术后3h时HIF-1α-BMSCs组鞘内注射HIF-1α修饰的BMSCs1×106个/5μl,BMSCs组给予BMSCs 1×106个/5μl.分别于治疗后1、3、7、14、28 d时进行BBB运动等级评分,然后取L2-5脊髓组织,测定HIF-1α mRNA及其蛋白表达.结果与S组比较,I/R组治疗后1、3、7、14、28 d时BBB运动等级评分降低,BMSCs组和HIF-1α-BMSCs组治疗后1、3、7、14 d时BBB运动等级评分降低(P＜0.05)；与I/R组比较,BMSCs组和HIF-1α-BMSCs组治疗后3、7、14、28 d时BBB运动等级评分升高,脊髓组织HIF-1α mRNA及其蛋白表达上调(P＜0.05)；与BMSCs组比较,HIF-1α-BMSCs组治疗后3、7、14 d时BBB运动等级评分升高,脊髓组织HIF-1α mRNA及其蛋白表达上调(P＜0.05).结论 HIF-1α基因修饰BMSCs移植治疗大鼠脊髓缺血再灌注损伤的效果较好.
목적 평개저양유도인자-1α(HIF-1α)기인수식골수간충질간세포(BMSCs)이식치료대서척수결혈재관주손상적효과.방법 성년건강웅성SD대서135지,2월령,체중200 ～ 300 g,채용수궤수자표법,장기분위4조:가수술조(S조,n =20)、결혈재관주조(I/R조,n=20)、BMSCs조(n=20)화HIF-1α기인수식BMSCs조(HIF-1α-BMSCs조,n=75).채용조단복주동맥45 min행재관주적방법제비대서척수결혈재관주손상모형,우술후3h시HIF-1α-BMSCs조초내주사HIF-1α수식적BMSCs1×106개/5μl,BMSCs조급여BMSCs 1×106개/5μl.분별우치료후1、3、7、14、28 d시진행BBB운동등급평분,연후취L2-5척수조직,측정HIF-1α mRNA급기단백표체.결과 여S조비교,I/R조치료후1、3、7、14、28 d시BBB운동등급평분강저,BMSCs조화HIF-1α-BMSCs조치료후1、3、7、14 d시BBB운동등급평분강저(P＜0.05)；여I/R조비교,BMSCs조화HIF-1α-BMSCs조치료후3、7、14、28 d시BBB운동등급평분승고,척수조직HIF-1α mRNA급기단백표체상조(P＜0.05)；여BMSCs조비교,HIF-1α-BMSCs조치료후3、7、14 d시BBB운동등급평분승고,척수조직HIF-1α mRNA급기단백표체상조(P＜0.05).결론 HIF-1α기인수식BMSCs이식치료대서척수결혈재관주손상적효과교호.
Objective To evaluate the effect of bone mesenchymal stem cells (BMSCs) modified with hypoxia-inducible factor-1α (HIF-1α) gene transplantation on spinal cord ischemia-reperfusion (I/R) injury in rats.Methods One hundred and thirty-five male Sprague-Dawley rats,aged 2 months,weighing 200-300 g,were used in this study.All the animals were divided into 4 groups:sham operation group (S group,n =20),I/R group (n=20),group BMSCs (n =20) and BMSCs modified with HIF-1α gene (HIF-1α-BMSCs) group (n =75).Spinal cord ischemia was induced by 45 min occlusion of the abdominal aorta followed by reperfusion.At 3 h after spinal cord I/R,HIF-1α-BMSCs 1 × 106 cells/5μl were injected intrathecally in group HIF-1α-BMSCs,and BMSCs 1 ×106 cells/5μl were given in group BMSCs.On day 1,3,7,14 and 28 after treatment,motor function was assessed using Basso,Beattie and Bresnahan (BBB) Locomotor Rating Scale,and the L2-5 spinal cord tissues of rats were obtained for determination of HIF-1α mRNA and protein expression.Results Compared with group S,BBB scores were significantly decreased on day 1,3,7,14 and 28 after treatment in group I/R,and on day 1,3,7 and 14 after treatment in groups BMSCs and HIF-1α-BMSCs (P ＜ 0.05).BBB scores were significantly increased and HIF-1α mRNA and protein expression was up-regulated on day 3,7,14 and 28 after treatment in groups BMSCs and HIF-1α-BMSCs as compared with group I/R (P ＜ 0.05).BBB scores were significantly increased and HIF-1α mRNA and protein expression was up-regulated on day 3,7 and 14 after treatment in group BMSCs as compared with group HIF-1α-BMSCs (P ＜ 0.05).Conclusion Implantation of BMSCs modified with HIF-1α gene can attenuate spinal cord I/R injury in rats.