骨髓间充质干细胞移植对实验性恢复期脑缺血大鼠神经功能恢复及Nogo-A、NgR、Rhoa和ROCK表达的影响
Effects of bone marrow mesenchymal stem cells transplantation on the recovery of neurological functions and the expression of Nogo-A, NgR, Rhoa, and ROCK in rats with experimentally-induced convalescent cerebral ischemia.
作者信息
Zhang Jianbo, Li Zhenjun, Liu Wenchao, Zeng Wenxian, Duan Chuanzhi, He Xuying
机构信息
Department of Neurosurgery, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Province Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Department of Neurosurgery, Southern Medical University, Zhujiang Hospital, Guangzhou 510282, China.
出版信息
Ann Transl Med. 2020 Mar;8(6):390. doi: 10.21037/atm.2020.03.144.
BACKGROUND
To investigate the effects of intravenous transplantation of bone marrow mesenchymal stem cells (BMSCs) on neurological function in rats with experimentally-induced convalescent cerebral ischemia and the expression of Nogo-A, NgR, Rhoa, and ROCK expression.
METHODS
BMSCs were isolated and cultured using the whole bone marrow adherent method. Eighty-one adult male Sprague-Dawley rats were divided at random into three groups: the sham-operated group, the cerebral ischemia group, and the BMSC treatment group (n=27 rats per group). In the latter two groups, the middle cerebral artery occlusion (MCAO) model was performed by the modified Zea Longa method. After MCAO, rats in the sham-operated and cerebral ischemic groups were injected with 1 mL of phosphate buffered saline (PBS) via the tail vein. In the BMSC-treatment group, 1 mL of the BMSC suspension (containing 3×10 BMSCs) was injected through the rats' femoral vein. At 12, 24, and 72 h after BMSC transplantation, modified neurological deficit scores (mNSS) were used to assess neurological function. TTC (2,3,5-triphenyl tetrazolium chloride) staining was used to measure the ischemic lesion volume, and the distribution of Nogo-A protein was observed by immunohistochemistry. The expressions of Nogo-A, NgR, Rhoa, and ROCK were detected by Western blot.
RESULTS
At 72 h after BMSC transplantation, the mNSS scores were significantly lower in the BMSC treatment group than those in the cerebral ischemia group (7.50±0.55 . 8.67±0.52, P<0.01), and the ischemic lesions volume was significantly reduced. The expressions of Nogo-A, NgR, RhoA, and ROCK were significantly decreased compared with the controls (P<0.05).
CONCLUSIONS
The transplantation of BMSCs can improve neurological function in rats after convalescent cerebral ischemia, and their therapeutic effect may be related to the downregulation of Nogo-A, NgR, RhoA, and ROCK expression.
背景
探讨静脉移植骨髓间充质干细胞（BMSCs）对实验性恢复期脑缺血大鼠神经功能及Nogo-A、NgR、Rhoa和ROCK表达的影响。
方法
采用全骨髓贴壁法分离培养BMSCs。81只成年雄性Sprague-Dawley大鼠随机分为三组：假手术组、脑缺血组和BMSC治疗组（每组27只大鼠）。后两组采用改良的Zea Longa法制作大脑中动脉闭塞（MCAO）模型。MCAO后，假手术组和脑缺血组大鼠经尾静脉注射1 mL磷酸盐缓冲盐水（PBS）。在BMSC治疗组，通过大鼠股静脉注射1 mL BMSC悬液（含3×10个BMSCs）。在BMSC移植后12、24和72小时，采用改良神经功能缺损评分（mNSS）评估神经功能。用2,3,5-三苯基氯化四氮唑（TTC）染色测量缺血灶体积，免疫组化观察Nogo-A蛋白分布。采用蛋白质免疫印迹法检测Nogo-A、NgR、Rhoa和ROCK的表达。
结果
BMSC移植后72小时，BMSC治疗组的mNSS评分显著低于脑缺血组（7.50±0.55 对8.67±0.52，P<0.01），缺血灶体积显著减小。与对照组相比，Nogo-A、NgR、RhoA和ROCK的表达显著降低（P<0.05）。
结论
BMSCs移植可改善恢复期脑缺血大鼠的神经功能，其治疗作用可能与下调Nogo-A、NgR、RhoA和ROCK表达有关。
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