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骨髓间充质干细胞通过影响 P21/PCNA 并抑制氧化应激来改善衰老大鼠的胸腺和脾脏功能。

Bone marrow mesenchymal stem cells improve thymus and spleen function of aging rats through affecting P21/PCNA and suppressing oxidative stress.

机构信息

Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, Fujian, China.

Department of Hematology, Fujian Provincial Hospital, Fuzhou 350001, Fujian, China.

出版信息

Aging (Albany NY). 2020 Jun 19;12(12):11386-11397. doi: 10.18632/aging.103186.

DOI:10.18632/aging.103186
PMID:32561691
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7343510/
Abstract

Bone marrow mesenchymal stem cells (BMSCs) have been considered to be an important regulator for immune function. We aim to prove the function improvement of aging spleen and thymus induced by BMSCs and unfold the specific mechanisms. Aging animal model was established using D-galactose. The morphological changes of spleen and thymus tissues were observed using hematoxylin-eosin staining and transmission electron microscopy. Key cytokines in the serum were measured with enzyme linked immunosorbent assay. Protein and mRNA levels of P16, P21, and PCNA were detected using western blotting and RT-qPCR. Special markers of BMSCs were identified using flow cytometry, and successful induction of BMSCs to steatoblast and osteoblasts was observed. Compared to aging model, BMSCs significantly increased the spleen and thymus index, improved the histological changes of spleen and thymus tissues. A remarkable increase of ratio between CD4+T cells and CD8+T cells, level of IL-2 was achieved by BMSCs. However, BMSCs markedly inhibited the content of IL-10, TNF-, P16, and P21 but promoted PCNA. Significant inhibition of oxidative stress by BMSCs was also observed. We demonstrated that BMSCs significantly improved the tissue damage of aging spleen and thymus, BMSCs may improve aging organs through influencing cytokines, oxidative stress, and P21/PCNA.

摘要

骨髓间充质干细胞（BMSCs）被认为是免疫功能的重要调节因子。我们旨在证明 BMSCs 对衰老脾脏和胸腺功能的改善作用，并揭示其具体机制。使用 D-半乳糖建立衰老动物模型。通过苏木精-伊红染色和透射电子显微镜观察脾脏和胸腺组织的形态变化。用酶联免疫吸附试验测定血清中关键细胞因子的水平。用 Western blot 和 RT-qPCR 检测 P16、P21 和 PCNA 的蛋白和 mRNA 水平。用流式细胞术鉴定 BMSCs 的特异性标志物，并观察 BMSCs 向成脂细胞和成骨细胞的成功诱导。与衰老模型相比，BMSCs 显著增加了脾脏和胸腺指数，改善了脾脏和胸腺组织的组织学变化。BMSCs 显著增加了 CD4+T 细胞和 CD8+T 细胞的比例和 IL-2 水平。然而，BMSCs 显著抑制了 IL-10、TNF-α、P16 和 P21 的含量，但促进了 PCNA。BMSCs 还显著抑制了氧化应激。我们证明 BMSCs 显著改善了衰老脾脏和胸腺的组织损伤，BMSCs 可能通过影响细胞因子、氧化应激和 P21/PCNA 来改善衰老器官。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/49274dd630a5/aging-12-103186-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/f5bc2a5346eb/aging-12-103186-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/e05d6d699c06/aging-12-103186-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/66db0bf61f0b/aging-12-103186-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/531e5b804fb7/aging-12-103186-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/49274dd630a5/aging-12-103186-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/f5bc2a5346eb/aging-12-103186-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/e05d6d699c06/aging-12-103186-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/66db0bf61f0b/aging-12-103186-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/531e5b804fb7/aging-12-103186-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc2/7343510/49274dd630a5/aging-12-103186-g005.jpg

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