肾纤维化(RF)代表慢性肾脏病(CKD)中最广泛的病理状况。最近,蛋白质戊烯化与纤维化的进展有关。该研究通过靶向蛋白质戊烯化检查了唑来膦酸(ZA)(50µg/kg/周)在四氯化碳(CCl4)诱导的RF大鼠模型中的肾脏保护作用。将40只Wistar雄性大鼠分成对照组,车辆处理组,模型-射频组,和RF-ZA组。平均动脉血压(MBP),BUN,血清肌酐,和尿白蛋白-肌酐比值(uACR),焦磷酸法尼酯(FPP)的蛋白质水平,肿瘤坏死因子-α(TNF-α),转化生长因子-β(TGF-β),丙二醛(MDA),并测定过氧化氢酶和法尼基焦磷酸合酶(FPPS)和核因子-kB(NF-κB)的基因表达。肾白细胞介素-6(IL-6)的免疫组织化学染色,α-平滑肌肌动蛋白(α-SMA),和caspase-3,以及组织病理学改变,被评估。ZA大大停止了MBP的降低,显著降低uACR,血清肌酐,BUN,和FPPS的表达,FPP,NF-κB,TGF-β,TNF-α,MDA,与RF模型大鼠相比,过氧化氢酶水平显着增加。ZA改善了CCl4诱导的组织病理学改变,并抑制了caspase-3,α-SMA的表达,IL-6总之,ZA在大鼠模型中保留肾功能并预防肾纤维化。这些是通过主要通过抑制FPPS靶向蛋白质异戊二烯化来实现的。
Renal fibrosis (RF) represents the most widespread pathological condition in chronic kidney disease (CKD). Recently, protein prenylation has been implicated in the fibrosis\'s progression. The research examined the renoprotective effect of zoledronic acid (ZA) (50 µg/kg/week) in a rat model of carbon tetrachloride (CCl4)-induced RF through targeting protein prenylation. Forty Wistar male rats were split up into the control group, vehicle-treated group, model-RF group, and RF-ZA group. Mean arterial blood pressure (MBP), BUN, serum creatinine, and urine albumin-creatinine ratio (uACR), protein levels of farnesyl pyrophosphate (FPP), tumour necrosis factor-alpha (TNF-α), transforming growth factor-β (TGF-β), and malondialdehyde (MDA), and catalase and gene expression of farnesyl pyrophosphate synthase (FPPS) and nuclear factor-kB (NF-κB) were measured. Immunohistochemical staining for renal interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and caspase-3, as well as histopathological alterations, were assessed. ZA considerably ceased the reduction in MBP, markedly reduced uACR, serum creatinine, BUN, and expression of FPPS, FPP, NF-κB, TGF-β, TNF-α, and MDA, and significantly increased catalase levels compared to the model-RF rats. ZA ameliorated the CCl4-induced histopathological alterations and suppressed the expression of caspase-3, α-SMA, and IL-6. In conclusion, ZA preserved renal function and prevented renal fibrosis in a rat model. These were achieved through targeting protein prenylation mainly by inhibiting FPPS.