Department of Physiology, School of Paramedical Sciences, Dezful University of Medical Sciences, Dezful, Iran.
Department of Physiology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran.
J Chem Neuroanat. 2021 Apr;113:101938. doi: 10.1016/j.jchemneu.2021.101938. Epub 2021 Feb 23.
Human amniotic membrane-derived mesenchymal stem cell-conditioned medium (hAMSC-CM) has been known to improve neuronal survival following ischemic stroke. The present study was designed to examine whether protective effects of hAMSC-CM against stroke can be linked to reducing neuroinflamation by targeting TLR4 /NF-ĸB and Jak2/Stat3 signaling pathways. Immunohistochemistry of hippocampus and western blot assay were performed to evaluate the expression of TLR4 /NF-ĸB and Jak2/Stat3, respectively. Real-time PCR assay was applied to investigate the mRNA levels of Jak2/Stat3. Hematoxylin and eosin (H&E) staining was used to investigate tissue damage and morphological changes in the CA1 region of hippocampus. Increased brain edema was seen in middle cerebral artery occlusion (MCAO) rats compared to sham. Post-treatment with hAMSC-CM markedly reduced brain edema in comparison with MCAO group (P < 0.05). Compared to sham, significantly increased levels of TLR4 /NF-ĸB and Jak2/Stat3 were seen in MCAO rats. Intravenous injection of hAMSC-CM after reperfusion markedly reduced levels of TLR4 /NF-ĸB and Jak2/Stat3 in hippocampus region (P < 0.05). Tissue damage and neuronal cell increased in the CA1 region of hippocampus that reversed by post-treatment by hAMSC-CM. Interestingly, our finding showed that hAMSC-CM can be considered as good candidate to reduce injury following ischemic stroke by decreasing activity of TLR4 /NF-ĸB and Jak2/Stat3 signaling pathways.
人羊膜间充质干细胞条件培养基（hAMSC-CM）已被证实可改善缺血性中风后的神经元存活。本研究旨在探讨 hAMSC-CM 对中风的保护作用是否可以通过靶向 TLR4/NF-κB 和 Jak2/Stat3 信号通路来减轻神经炎症。通过免疫组织化学法检测海马 TLR4/NF-κB 和 Jak2/Stat3 的表达，western blot 法检测海马 Jak2/Stat3 的表达，实时 PCR 法检测 Jak2/Stat3 的 mRNA 水平。苏木精-伊红（H&E）染色观察海马 CA1 区组织损伤和形态学变化。与假手术组相比，大脑中动脉闭塞（MCAO）大鼠的脑水肿明显增加。与 MCAO 组相比，hAMSC-CM 治疗后脑水肿明显减少（P<0.05）。与假手术组相比，MCAO 大鼠 TLR4/NF-κB 和 Jak2/Stat3 水平显著升高。再灌注后静脉注射 hAMSC-CM 可显著降低海马 TLR4/NF-κB 和 Jak2/Stat3 水平（P<0.05）。MCAO 大鼠海马 CA1 区组织损伤和神经元细胞增多，经 hAMSC-CM 治疗后得到逆转。有趣的是，我们的研究结果表明，hAMSC-CM 可通过降低 TLR4/NF-κB 和 Jak2/Stat3 信号通路的活性，被认为是减轻缺血性中风后损伤的良好候选物。
