抑制lncRNA H19表达促进脑缺血小鼠神经功能康复的研究  

Inhibition of lncRNA H19 Expression Promotes Neurological Rehabilitation after Ischemic Stroke in Mice

作　　者：巴珠 普布次仁 吴刚 胡枢坤 BA Zhu;PUBU Ci-ren;WU Gang;HU Shu-kun(Department of Neurosurgery,People's Hospital of Shigatse City,Shigatse City 857000,China;Department of Neurosurgery,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]西藏自治区日喀则市人民医院神经外科,日喀则857000 [2]复旦大学附属华山医院神经外科,上海200040

出　　处：《中国临床神经科学》2024年第5期496-501,共6页Chinese Journal of Clinical Neurosciences

基　　金：西藏自治区自然科学基金组团式医学援藏项目(编号:XZ2019ZR-ZY41)。

摘　　要：目的 探讨长非编码RNA(lnc RNA)H19(简称H19)在小鼠缺血性脑卒中(IS)康复过程中的作用。方法 建立小鼠大脑中动脉闭塞(MCAO)IS模型。根据干预方式不同,分为假手术组、MACO组、MACO-对照组和MACO+sh H19组(采用病毒转染技术,立体定向下小鼠脑内注射AAV2/1-sh RNA-H19抑制H19的表达)。通过前肢伸展功能、握力和胶带移除三项行为学测试评估小鼠的神经功能变化;PCR检测脑内H19和胰岛素样生长因子1受体(IGFR1)含量,免疫荧光双染计数m TOR信号通路关键蛋白PS6的阳性细胞数。结果 MACO组脑内H19的含量较假手术组明显上升,术后1 d时最为显著,AAV2/1-sh RNA-H19可以抑制脑内H19的表达。行为学实验结果显示,MACO+sh H19组在术后4周时,小鼠前肢伸展功能和胶带移除的测试优于MACO-对照组,8周时差异更为明显;术后8周时,MACO+sh H19组握力测试明显好于MACO组。抑制MACO+sh H19组的H19表达可以显著上调IGFR1和PS6水平。结论 抑制H19表达可以促进小鼠IS后神经功能的康复,其作用机制可能与IGFR1和PS6的上调有关。Aim To investigated the role of long non-coding RNA(lncRNA) H19 in the rehabilitation of ischemic stroke in mice. Methods The mouse model of ischemic stroke with middle artery occlusion(MCAO) was established. Mice were divided into four groups: a sham group, a MACO group, a MACO-control group and a MACO+shH19 group(AAV2/1-shRNA-H19 was injected into the brain under stereotactic navigation to inhibit the expression of H19 using virus transfection technology).The neurological function changes in mice were evaluated by behavioral tests, which included forearm extension function, tape removal and grip strength test. The expression of H19 and insulin-like growth factor 1 receptor(IGFR1) in the cortex was detected by PCR. The positive cells of PS6, which is the key protein of mTOR pathway, was counted by immunofluorescence double staining. Results The level of H19 in the brain of MACO group was significantly higher than that of the sham group, and the most significant level was at 1 day after operation.The expression of H19 in the brain could be inhibited by AAV2/1-sh RNA-H19.The MACO+sh H19 group showed better performance in forearm extension function and tape removal test at 4 weeks after stroke compared to the MACO-control group,and the most significant differences occurred at 8 weeks.The grip strength test of MACO+sh H19 group was significantly better than that of MACO group 8 weeks after operation.Inhibition of H19 expression in MACO+sh H19 group can significantly upregulate the levels of IGFR1 and PS6 in the brain.Conclusion The inhibition of H19 can promote the rehabilitation of neurological function in mice after ischemic stroke,and its effect may be related to the upregulation of IGFR1 and PS6.

关 键 词：缺血性脑卒中 长非编码RNA H19 神经功能康复 

分 类 号：R7[医药卫生—临床医学] R743