Study on the Therapeutic Effects and Mechanisms of Human Mesenchymal Stem Cell-Derived Exosomes Carrying NGF Gene in Treating Ischemic Stroke in Rats

Proceedings of Anticancer Research Pub Date : 2024-08-09 DOI:10.26689/par.v8i4.7897

Bing Li, Xuanxuan Xu, Wenqin Zhou, Peng Wang

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Abstract

Objective: To investigate the therapeutic effects and mechanisms of human mesenchymal stem cell-derived exosomes (hMSCs-Exo) carrying the NGF gene in treating ischemic stroke in rats, aiming to provide new insights and treatment methods for ischemic stroke therapy. Methods: After successful construction of the cerebral ischemia model in 40 male SPF-grade SD rats aged 6–8 weeks, the model rats were randomly divided into 4 groups: Sham group, PBS group, hMSCs-Exo group, and NGF-hMSCs-Exo group, with 10 rats in each group. The rat MCAO model was prepared using the classic filament method, and NGF-hMSCs-Exo were injected via the tail vein into the MCAO model rats. The expression of the NGF gene in brain ischemic tissues, neuronal regeneration, and rat neurological function recovery were observed using TTC staining, memory function evaluation, Western blot, qRT-PCR, and other methods. Results: Compared with the Sham group, neurological deficits were significant in the PBS group (P < 0.01). Compared with the PBS group, neurological scores improved in the hMSCs-Exo group and NGF-hMSCs-Exo group (P < 0.05). Compared with the hMSCs-Exo group, the improvement in neurological deficits was more significant in the NGF-hMSCs-Exo group (P < 0.05). The infarct area after NGF-hMSCs-Exo intervention was significantly reduced (P < 0.05) compared with the Sham group. Compared with the PBS group, relative expression levels of NGF mRNA and protein decreased, while Caspase-3 mRNA and protein expression significantly increased in the PBS group (P < 0.01). Compared with the PBS group and hMSCs-Exo group, there were differences in NGF and Caspase-3 mRNA and protein expression in the NGF-hMSCs-Exo group rat brain tissues (P < 0.05). Conclusion: Treatment with human mesenchymal stem cell-derived exosomes carrying the NGF gene improves cognitive function and exerts protective effects on SD rats while inhibiting apoptotic levels in cells.

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携带 NGF 基因的人间质干细胞衍生外泌体治疗缺血性脑卒中大鼠的疗效及机制研究

目的研究携带NGF基因的人间质干细胞外泌体（hMSCs-Exo）治疗缺血性脑卒中大鼠的疗效和机制，旨在为缺血性脑卒中的治疗提供新的见解和治疗方法。研究方法将 40 只 6-8 周龄的雄性 SPF 级 SD 大鼠成功构建脑缺血模型后，将模型大鼠随机分为 4 组：Sham 组、PBS 组、hMSCs-Exo 组和 NGF-hMSCs-Exo 组，每组 10 只。大鼠MCAO模型的制备采用经典的丝状法，NGF-hMSCs-Exo经尾静脉注射到MCAO模型大鼠体内。采用TTC染色、记忆功能评价、Western blot、qRT-PCR等方法观察NGF基因在脑缺血组织中的表达、神经元再生及大鼠神经功能恢复情况。结果与 Sham 组相比，PBS 组神经功能缺损明显（P < 0.01）。与 PBS 组相比，hMSCs-Exo 组和 NGF-hMSCs-Exo 组的神经功能评分有所改善（P < 0.05）。与 hMSCs-Exo 组相比，NGF-hMSCs-Exo 组的神经功能缺损改善更为显著（P < 0.05）。与 Sham 组相比，NGF-hMSCs-Exo 干预后的梗死面积明显缩小（P < 0.05）。与 PBS 组相比，PBS 组 NGF mRNA 和蛋白的相对表达水平降低，而 Caspase-3 mRNA 和蛋白的表达水平明显升高（P < 0.01）。与 PBS 组和 hMSCs-Exo 组相比，NGF-hMSCs-Exo 组大鼠脑组织中 NGF 和 Caspase-3 mRNA 及蛋白表达存在差异（P < 0.05）。结论用携带NGF基因的人类间充质干细胞衍生外泌体治疗SD大鼠，可改善其认知功能并发挥保护作用，同时抑制细胞凋亡水平。

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Proceedings of Anticancer Research

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