广东医学2025，Vol.46Issue(9)：1293-1299,7.DOI:10.13820/j.cnki.gdyx.20250001
尼可地尔通过调控热休克蛋白-70对大鼠造影剂相关急性肾损伤的影响
Effect of nicorandil on contrast-induced acute kidney injury in rats via regulation of heat shock protein-70
摘要
Abstract
Objective To investigate the effect of nicorandil on contrast-induced acute kidney injury(CA-AKI)in rats and its underlying mechanism involving heat shock protein-70(HSP-70).Methods Sprague-Dawley rats were randomly divided into five groups:control,CA-AKI,nicorandil,VER-155008(HSP-70 inhibitor),and nicorandil+VER-155008.The control and CA-AKI groups received saline by gavage before modeling.The nicorandil group received nicorandil(5 mg/kg,gavage),the VER-155008 group received VER-155008(10 μmol/kg,intraper-itoneal injection),and the combined group received both drugs.Treatments were administered for seven consecutive days,followed by CA-AKI induction in all groups except the control.Twelve hours post-modeling,renal function was as-sessed by serum creatinine(Scr),blood urea nitrogen(BUN),neutrophil gelatinase-associated lipocalin(NGAL),and kidney injury molecule-1(KIM-1).Renal histopathological injury and fibrosis were evaluated by hematoxylin-eosin and Masson staining,respectively.Levels of interleukin-1 β(IL-1β),interleukin-18(IL-18),tumor necrosis fac-tor-α(TNF-α),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),apop-tosis rate,cleaved caspase-3,and HSP-70 expression were measured.Results Compared with the control group,the CA-AKI group exhibited significantly elevated Scr,BUN,NGAL,KIM-1,histological injury score,fibrotic area,renal IL-1 β,IL-18,TNF-α,MDA,apoptosis rate,cleaved caspase-3,and HSP-70 expression(t=22.362,24.654,19.513,13.871,28.886,17.407,15.458,11.349,13.991,14.004,25.796,27.500,7.542,P＜0.05),while SOD and GSH-Px levels were decreased(t=8.167,8.931,P＜0.05).Compared with the CA-AKI group,nicorandil treatment significantly reduced Scr,BUN,NGAL,KIM-1,histological injury score,fibrotic area,IL-1β,IL-18,TNF-α,MDA,apoptosis rate,and cleaved caspase-3(t=13.415,15.834,12.369,11.396,17.903,11.204,10.369,7.663,4.629,10.219,18.295,13.156,P＜0.05),while increasing SOD,GSH-Px,and HSP-70 expres-sion(t=6.489,6.890,12.257,P＜0.05).Scr,BUN,NGAL,KIM-1,renal tubule pathological injury score,the relative area of renal tubulointerstitial fibrosis,IL-1 beta,IL-18,IL-1β,IL-18,TNF-α,MDA levels,apoptosis rate and cleaved caspase-3 expression levels in kidney of nicorandil+VER-155008 group were higher than those in nic-orandil group(t=11.256,9.846,7.668,4.992,10.095,9.266,8.537,6.219,8.360,6.078,14.640,11.853,P＜0.05),SOD,GSH-Px levels and HSP-70 expression levels were lower than those of nicorandil group(t=6.078,4.661,5.588,P＜0.05).Conclusion Nicorandil alleviates contrast-induced acute kidney injury in rats by upregulat-ing HSP-70 expression.This effect is associated with reduced renal inflammation,oxidative stress,and apoptosis.关键词
造影剂相关急性肾损伤/尼可地尔/热休克蛋白-70/炎症反应/氧化应激/细胞凋亡Key words
contrast-induced acute kidney injury/nicorandil/heat shock protein-70/inflammation/oxidative stress/apoptosis分类
医药卫生引用本文复制引用
朱波,饶海微,宣睿,李青,詹碧鸣..尼可地尔通过调控热休克蛋白-70对大鼠造影剂相关急性肾损伤的影响[J].广东医学,2025,46(9):1293-1299,7.基金项目
江西自然科学基金(20232BAB216003) （20232BAB216003）
江西省教育厅科学技术研究项目(170159) （170159）
