骨髓间充质干细胞衍生的外泌体通过抑制细胞凋亡和炎症缓解大鼠糖尿病肾病。
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Diabetic Kidney Disease in Rats by Inhibiting Apoptosis and Inflammation.
机构信息
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China.
Department of Cardiology, The Second Affiliated Hospital of Shandong First Medical University, 271000 Taian, Shandong, China.
出版信息
Front Biosci (Landmark Ed). 2023 Sep 14;28(9):203. doi: 10.31083/j.fbl2809203.
BACKGROUND AND AIMS
Previous studies have confirmed the anti-inflammation effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo). We aimed to investigate the therapeutic effect of BMSC-Exo on diabetic kidney disease (DKD), as well as the underlying mechanisms.
METHODS
SD rats were induced by streptozotocin combined with a high-fat diet to establish a diabetes disease model. BMSCs-Exo were injected via tail veins at a weekly dose of 100 µg for 12 weeks. Pathological changes in the rat kidneys were evaluated using HE, Masson, and Periodic Acid-Schiff and immunohistochemical staining. TUNEL staining and western blot were used to evaluate the expression levels of apoptosis-related proteins in the rat kidney cells. The TNF-α level was detected by PCR and NF-κB (p65) by western blotting to examine the inflammatory responses in the renal tissue.
RESULTS
BMSCs-Exo significantly alleviated the renal structural damage and the distribution of apoptotic cells in diabetic rats. Furthermore, BMSCs-Exo increased the expression of pro-apoptosis protein Bax and decreased the expression of apoptosis-executing protein Cleaved Caspase 9 and Cleaved caspase 3. In addition, the transcription level of TNF-α in kidney tissue and NF-κB (p65) expression was also decreased through BMSCs-Exo treatment. Besides, the levels of glucose (GLU), creatinine (Cr), and burea nitrogen (BUN) in diabetic rats were decreased by the BMSC-Exo treatment.
CONCLUSIONS
BMSCs-Exo may alleviate diabetic kidney damage by inhibiting apoptosis and inflammation.
背景与目的
先前的研究已经证实骨髓间充质干细胞来源的外泌体（BMSC-Exo）具有抗炎作用。我们旨在研究 BMSC-Exo 对糖尿病肾病（DKD）的治疗作用及其潜在机制。
方法
SD 大鼠通过链脲佐菌素联合高脂饮食诱导建立糖尿病疾病模型。每周通过尾静脉注射 BMSC-Exo 100μg，持续 12 周。使用 HE、Masson、过碘酸希夫和免疫组织化学染色评估大鼠肾脏的病理变化。TUNEL 染色和 Western blot 用于评估大鼠肾脏细胞中凋亡相关蛋白的表达水平。通过 PCR 检测 TNF-α 水平，通过 Western blot 检测 NF-κB（p65），以检查肾脏组织中的炎症反应。
结果
BMSC-Exo 显著减轻了糖尿病大鼠的肾脏结构损伤和凋亡细胞的分布。此外，BMSC-Exo 增加了促凋亡蛋白 Bax 的表达，降低了凋亡执行蛋白 Cleaved Caspase 9 和 Cleaved caspase 3 的表达。此外，通过 BMSC-Exo 处理还降低了肾脏组织中 TNF-α 的转录水平和 NF-κB（p65）的表达。此外，BMSC-Exo 治疗还降低了糖尿病大鼠的血糖（GLU）、肌酐（Cr）和尿素氮（BUN）水平。
结论
BMSC-Exo 可能通过抑制细胞凋亡和炎症来减轻糖尿病肾病的损伤。
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