关键词: BM-MSCs CCl4 Kidney toxicity inflammatory and apoptotic markers oxidative stress rats

Mesh : Animals Male Mice Rats Acute Kidney Injury / metabolism therapy pathology chemically induced Carbon Tetrachloride / toxicity Cyclooxygenase 2 / metabolism Disease Models, Animal Fibrosis Kidney / pathology Lipid Peroxidation Mesenchymal Stem Cell Transplantation / methods Mesenchymal Stem Cells / metabolism Oxidative Stress Rats, Wistar Tumor Necrosis Factor-alpha / metabolism

来  源:   DOI:10.1080/0886022X.2024.2319330   PDF(Pubmed)

Abstract:
UNASSIGNED: This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl4) in Wistar rats.
UNASSIGNED: Following an intraperitoneal injection of CCl4 (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 106 cells in 0.2 mL Dulbecco\'s Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson\'s trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue.
UNASSIGNED: In CCl4-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl4-injected rats considerably reduced the previously noted abnormalities.
UNASSIGNED: By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl4 injections.
摘要:
本研究探讨了大鼠和小鼠骨髓间充质干细胞(BM-MSCs)对四氯化碳(CCl4)对Wistar大鼠肾损伤和毒性的可能治疗作用。
腹膜内注射CCl4(0.5mL/kg,每周两次)八周后,雄性Wistar大鼠每周用大鼠和小鼠BM-MSC(0.2mLDulbecco's改良Eagle培养基(DMEM)中的1×106个细胞/大鼠/周)静脉内治疗,持续4周。使用苏木精和曙红(H&E)评估肾功能并检查肾脏样本,Masson三色(MT)染色技术,和电子显微镜分析。肾环氧合酶-2(COX-2),蛋白53(p53),免疫组织化学染色技术检测肿瘤坏死因子-α(TNF-α)。此外,在肾脏组织中鉴定了氧化应激和抗氧化防御系统的生物指标。
在注射CCl4的大鼠中,血清肌酐,尿素,尿酸水平显著上升,肾脏脂质过氧化(LPO),而超氧化物歧化酶,谷胱甘肽过氧化物酶(GPx),谷胱甘肽(GSH)转移酶,肾脏的GSH水平显著下降。组织学上,肾脏表现出广泛的结构异常,如肾小球收缩,肾小管扩张术,炎性白细胞浸润,成纤维细胞增殖,胶原蛋白含量升高。炎性细胞因子如COX-2和TNF-α以及促凋亡介质p53显著上调。用注射CCl4的大鼠处理来自小鼠和大鼠的BM-MSC显著减少了先前注意到的异常。
通过增强抗氧化防御,减少细胞凋亡和炎症,来自小鼠和大鼠的BM-MSC能够增强接受CCl4注射的大鼠的肾功能和组织学完整性。
公众号