间充质干细胞对实验性自身免疫性脑脊髓炎小鼠铁死亡的影响

doi:10.6040/j.issn.1671-7554.0.2024.0265

摘要/Abstract

摘要： 目的探讨间充质干细胞(mesenchymal stem cells, MSCs)治疗对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis, EAE)小鼠铁死亡状况及关键调控蛋白表达的影响。方法记录每日小鼠体质量和行为表现,切片染色观察小鼠脊髓中炎症及脱髓鞘情况。通过检测还原型谷胱甘肽还原酶(reduced glutathione, GSH)、丙二醛(malondialdehyde, MDA)及总超氧化物歧化酶(total superoxide dismutase, T-SOD)观察小鼠组织中铁死亡状况,并检测转铁蛋白受体-1(transferrin receptor 1, TFR1)、酰基辅酶A合酶-4(acyl-CoA synthetase long-chain family 4, ACSL4)、谷胱甘肽过氧化酶-4(glutathione peroxidase 4, GPX4)及铁死亡抑制蛋白1(ferroptosis suppressor protein, FSP1)等调控蛋白的表达。结果 MSCs可以有效改善EAE小鼠体质量下降和症状表现。病理水平上,MSCs注射可以改善小鼠脊髓中炎细胞浸润及脱髓鞘。MSCs注射后,EAE小鼠脊髓和脑GSH含量升高(P<0.01,P<0.05)、脊髓T-SOD活力升高(P<0.01),脑中MDA含量下降(P<0.05)。MSCs治疗可以降低 EAE小鼠脊髓和脑中TFR1(P<0.05,P<0.01)、ACSL4蛋白表达(P<0.05, P<0.001),提高脊髓和脑中FSP1蛋白表达(P均<0.05)和脑中GPX4蛋白表达(P<0.05)。结论 MSCs通过调节铁代谢、脂代谢和促进活性氧清除来抑制EAE小鼠中铁死亡,发挥治疗作用。

关键词: 多发性硬化, 实验性自身免疫性脑脊髓炎, 间充质干细胞, 铁死亡, 铁代谢

Abstract: Objective To investigate the effects of mesenchymal stem cells(MSCs)treatment on ferroptosis and expressions of key regulatory proteins in experimental autoimmune encephalomyelitis(EAE)mice. Methods The body weights and symptom scores of mice were evaluated daily. To assess conditions of inflammation and myelination in spinal cord, the sections were respectively stained. The contents of reduced glutathione(GSH), malondialdehyde(MDA)and total superoxide dismutase(T-SOD)were tested to detect ferroptosis. The protein expressions of transferrin receptor 1(TFR1), acyl-CoA synthetase long-chain family 4(ACSL4), glutathione peroxidase 4(GPX4)and ferroptosis suppressor protein 1(FSP1)were detected with Western blotting. Results MSCs treatment alleviated weight loss and symptoms of EAE mice. Pathologically, MSCs improved infiltration of inflammatory cells and remyelination of mice. MSCs upregulated the contents of GSH in spinal cord and brain(P<0.01, P<0.05), as well as T-SOD in spinal cord(P<0.01), and downregulated MDA concentration in brain(P<0.05). Besides, MSCs reduced the protein expressions of TFR1(P<0.05, P<0.01)and ACSL4(P<0.05, P<0.001), increased the protein expressions of FSP1(both P<0.05)in spinal cord and brain. Also, the protein expression of GPX4 in brain was promoted after MSCs treatment(P<0.05). Conclusion MSCs play a therapeutic role in inhibiting ferroptosis in EAE mice by regulating iron metabolism, lipid metabolism and promoting reactive oxygen species clearance.

Key words: Multiple sclerosis, Experimental autoimmune encephalomyelitis, Mesenchymal stem cells, Ferroptosis, Iron metabolism

中图分类号:

R741

刘海霞,皇甫莎莎,桑晓玉,崔东清,毕建忠,王萍. 间充质干细胞对实验性自身免疫性脑脊髓炎小鼠铁死亡的影响[J]. 山东大学学报 (医学版), 2024, 62(6): 1-8.

LIU Haixia, HUANGFU Shasha, SANG Xiaoyu, CUI Dongqing, BI Jianzhong, WANG Ping. Effects of mesenchymal stem cells on ferroptosis in experimental autoimmune encephalomyelitis mice[J]. Journal of Shandong University (Health Sciences), 2024, 62(6): 1-8.

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