长期暴露于氯化铝(AlCl3)等重金属可能会导致严重的健康危害,例如慢性肾损伤。本研究旨在评估脂肪组织来源的干细胞(ASCs)与它们的微囊泡(MV)在AlCl3诱导的慢性肾损伤中的治疗潜力。48只成年雄性Wistar大鼠分为4组:对照组,AlCl3处理组,AlCl3/ASC治疗组,和AlCl3/MV处理组。生化研究包括血清尿素和肌酐水平的估计,氧化生物标志物测定,抗氧化剂生物标志物,血清细胞因子(IL-1β,IL-8、IL-10和IL-33),肾组织MALT1,TNF-α,IL-6和血清miR-150-5p表达水平。组织病理学研究包括肾组织的光和电子显微镜检查,马洛里三色染色纤维化,用于碳水化合物的组织化学检测的周期性酸性希夫(PAS)染色,和免疫组化检测Caspase-3作为凋亡标志物,IL-1B作为促炎细胞因子和CD40作为MV的标志物。AlCl3显著恶化肾功能,增强肾脏MDA和TOS,和血清细胞因子浓度,同时降低了抗氧化参数(SOD,GSH,和TAC)。此外,血清IL-10,TNF-α,miR-150-5p,且肾组织MALT1表达值均显著高于其他组。与其他组相比,肾脏切片显示肾皮质和髓质的组织病理学损伤明显,细胞凋亡增强,炎性细胞因子免疫表达增加。ASC和MV施用均改善了先前的参数水平,在MV治疗组中检测到更多改善。结论:ASC衍生的MV对慢性肾脏疾病具有有希望的改善作用。
Chronic exposure to heavy metals as aluminum chloride (AlCl3) could result in severe health hazards such as chronic renal injury. The present study aimed to evaluate the therapeutic potential of adipose tissue-derived stem cells (ASCs) in comparison to their
microvesicles (MV) in AlCl3-induced chronic renal injury. Forty-eight adult male Wistar rats were divided into four groups: Control group, AlCl3-treated group, AlCl3/ASC-treated group, and AlCl3/MV-treated group. Biochemical studies included estimation of serum urea and creatinine levels, oxidative biomarkers assay, antioxidant biomarkers, serum cytokines (IL-1β, IL-8, IL-10, and IL-33), real time-PCR analysis of renal tissue MALT1, TNF-α, IL-6, and serum miR-150-5p expression levels. Histopathological studies included light and electron microscopes examination of renal tissue, Mallory trichrome stain for fibrosis, Periodic acid Schiff (PAS) stain for histochemical detection of carbohydrates, and immunohistochemical detection of Caspase-3 as apoptosis marker, IL-1B as a proinflammatory cytokine and CD40 as a marker of MVs. AlCl3 significantly deteriorated kidney function, enhanced renal MDA and TOS, and serum cytokines concentrations while decreased the antioxidant parameters (SOD, GSH, and TAC). Moreover, serum IL-10, TNF-α, miR-150-5p, and renal MALT1 expression values were significantly higher than other groups. Kidney sections showed marked histopathological damage in both renal cortex and medulla in addition to enhanced apoptosis and increased inflammatory cytokines immunoexpression than other groups. Both ASCs and MVs administration ameliorated the previous parameters levels with more improvement was detected in MVs-treated group. In conclusion: ASCs-derived MVs have a promising ameliorating effect on chronic kidney disease.