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人骨髓间充质干细胞移植对大脑中动脉闭塞模型大鼠神经元再生的治疗作用。

Therapeutic effect of transplantation of human bone marrow‑derived mesenchymal stem cells on neuron regeneration in a rat model of middle cerebral artery occlusion.

机构信息

Department of Chinese Traditional Medicine, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, Hubei 430060, P.R. China.

Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

出版信息

Mol Med Rep. 2019 Oct;20(4):3065-3074. doi: 10.3892/mmr.2019.10536. Epub 2019 Jul 30.

Abstract

Human bone marrow‑derived mesenchymal stromal cells (hBMSCs) have been revealed to be beneficial for the regeneration of tissues and cells in several diseases. The present study aimed to elucidate the mechanisms underlying the effect of hBMSC transplantation on neuron regeneration in a rat model of middle cerebral artery occlusion (MCAO). The hBMSCs were isolated, cultured and identified. A rat model of MCAO was induced via the modified Longa method. Neurological severity scores (NSS) were adopted for the evaluation of neuronal function in the model rats after cell transplantation. Next, the expression levels of nestin, β‑III‑tubulin (β‑III‑Tub), glial fibrillary acidic protein (GFAP), HNA and neuronal nuclear antigen (NeuN) were examined, as well as the positive expression rates of human neutrophil alloantigen (HNA), nestin, NeuN, β‑III‑Tub and GFAP. The NSS, as well as the mRNA and protein expression of nestin, decreased at the 1st, 2nd, 4 and 8th weeks, while the mRNA and protein expression of NeuN, β‑III‑Tub and GFAP increased with time. In addition, after treatment, the MCAO rats showed decreased NSS and mRNA and protein expression of nestin, but elevated mRNA and protein expression of NeuN, β‑III‑Tub and GFAP at the 2nd, 4 and 8th weeks, and decreased positive expression of HNA and nestin with enhanced expression of NeuN, β‑III‑Tub and GFAP. Therefore, the present findings demonstrated that hBMSC transplantation triggered the formation of nerve cells and enhanced neuronal function in a rat model of MCAO.

摘要

人骨髓间充质基质细胞(hBMSCs)已被证明对几种疾病的组织和细胞再生有益。本研究旨在阐明 hBMSC 移植对大脑中动脉闭塞(MCAO)大鼠模型中神经元再生的作用机制。分离、培养和鉴定 hBMSCs。采用改良的 Longa 法诱导大鼠 MCAO 模型。细胞移植后,采用神经功能严重程度评分(NSS)评估模型大鼠的神经元功能。然后,检测巢蛋白、β-III-微管蛋白(β-III-Tub)、胶质纤维酸性蛋白(GFAP)、HNA 和神经元核抗原(NeuN)的表达水平,以及人中性粒细胞同种抗原(HNA)、巢蛋白、NeuN、β-III-Tub 和 GFAP 的阳性表达率。NSS 以及巢蛋白、β-III-Tub 和 GFAP 的 mRNA 和蛋白表达水平在第 1、2、4 和 8 周时降低,而 NeuN 的 mRNA 和蛋白表达水平随时间增加。此外,治疗后,MCAO 大鼠的 NSS 降低,巢蛋白的 mRNA 和蛋白表达降低,但第 2、4 和 8 周时 NeuN、β-III-Tub 和 GFAP 的 mRNA 和蛋白表达升高,HNA 和巢蛋白的阳性表达降低,而 NeuN、β-III-Tub 和 GFAP 的表达升高。因此,本研究结果表明,hBMSC 移植可触发神经细胞的形成,并增强 MCAO 大鼠的神经元功能。

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