目的:慢性肾脏病(CKD)是一个全球性的非传染性健康问题。纤维化被认为是CKD的基础和命运;因此,本研究的目的是评估钼酸钠对顺铂诱导的CKD模型的影响,并阐明可能的相关机制.
方法:在顺铂模型中,Wistar大鼠接受顺铂(1mg/kg,i.p.)每周两次,共十周。钼酸钠(100和200mg/kg,口服)在顺铂前一周给予,并在接下来的十周内每天继续给予。
结果:施用钼酸钠可改善肾功能,并显着减轻肾脏组织病理学切片的病理变化。此外,它通过增加SOD和GSH的水平和降低MDA的水平来调节氧化应激参数。同样,在肾匀浆中,钼酸钠减轻炎症,表明NF-κB和TNF-α水平显着降低。此外,它改善了纤维化,这表明在皮质和髓质中Masson的毛状体染色减少。肾切片对TGF-β1的免疫组织化学染色显示肾小球和肾小管蛋白阳性表达减少。此外,它降低了促纤维化Smad3水平和增加了抗纤维化Smad7水平。
结论:钼酸钠对顺铂诱导的大鼠CKD/纤维化有希望的抑制作用。这种作用可能是通过抑制TGF-β/Smad信号通路和上调Smad7表达导致细胞外胶原积累减少。此外,它们可以通过降低NF-κB和TNF-α水平来改善炎症,ROS减少,和恢复抗氧化防御。
OBJECTIVE: Chronic kidney disease (CKD) is a global non-communicable health problem. Fibrosis is considered the base and the fate of CKD; thus, the goal of this study was to evaluate the effects of sodium molybdate on cisplatin-induced CKD model and demonstrate the possible involved mechanisms.
METHODS: In cisplatin model, Wistar rats were challenged with cisplatin (1 mg/kg, i.p.) twice weekly for ten weeks. Sodium molybdate (100 and 200 mg/kg, orally) was given one-week prior cisplatin and was continued daily for the next ten weeks.
RESULTS: Administration of sodium molybdate amended kidney function and significantly reduced the pathological changes in renal histopathological sections. Moreover, it modulates oxidative stress parameters by increasing the levels of SOD and GSH and decreasing the level of MDA. Likewise, in renal homogenate, sodium molybdate attenuated inflammation that was revealed by NF-κB and TNF-α levels significant reduction. Additionally, it ameliorated fibrosis that was indicated by decreased Masson\'s trichome staining in cortex and medulla. Immunohistochemical staining of renal sections against TGF-β1 showed reduction of positive glomerular and tubular protein expression. Additionally, it decreased profibrotic Smad3 level and increased antifibrotic Smad7 level.
CONCLUSIONS: Administration of sodium molybdate demonstrated a hopeful suppressor effect on cisplatin-induced CKD/fibrosis in rat model. This effect may be through the inhibition pof TGF-β/Smad signaling pathway and up-regulation of Smad7 expression leading to decreased extracellular collagen accumulation. Moreover, they could ameliorate the inflammation through NF-κB and TNF-α levels reduction, decrease in ROS, and retrieval of antioxidant defenses.