山东医药2024，Vol.64Issue(27)：21-25,5.DOI:10.3969/j.issn.1002-266X.2024.27.005
tBHQ对膜性肾病大鼠肾组织损伤、氧化应激抑制及肾皮质和细胞核Nrf2/NF-κB信号通路调控作用
Inhibitory effects of tBHQ on renal injury and oxidative stress and its regulatory effect on Nrf2/NF-κB signaling pathway in renal cortex and nucleus of rats with membranous nephropathy
摘要
Abstract
Objective To observe the inhibitory effects of tert-butylhydroquinone(tBHQ)on renal injury and oxida-tive stress and its regulatory effect on the nuclear factor erythroid 2-related factor 2(Nrf2)/nuclear factor-κB(NF-κB)sig-naling pathway in renal cortex and nucleus of rats with membranous nephropathy(MN),so as to illustrate the potential therapeutic effect and mechanism of tBHQ on MN.Methods Thirty-two rats were randomly divided into the normal con-trol group,tBHQ control group,model group,and tBHQ intervention group,respectively.Rats in the normal control group were injected intraperitoneally with 3 mL of normal rabbit serum,rats in the tBHQ control group were injected with normal rabbit serum in the same way and then were gavaged with 50 mg/kg tBHQ once a day for a total of 15 injections,rats in the model group were injected intraperitoneally with 3 mL of rabbit Fx1A antiserum to establish passive Heymann ne-phritis(PHN)models,and rats in the tBHQ intervention group were injected with rabbit Fx1A antiserum in the same way and then were gavaged with 50 mg/kg tBHQ once a day for a total of 15 injections.At the end of the experiment,indicators related to nephrotic syndrome[24 h urinary protein(24 h-UPro),serum albumin(ALB),total cholesterol(T-CHOL),tri-glyceride(TG),high-density lipoprotein(HDL),and low-density lipoprotein(LDL)],renal function-related indicators[serum creatinine(sCr),urea nitrogen],renal podocyte injury(podocyte foot process fusion,glomerular Podocin/Des-min expression and distribution),renal cortex oxidative stress markers[malondialdehyde(MDA),8-isoprostaglandin(8-iso-PG),8-hydroxydeoxyguanosine(8-OHDG)],renal cortex antioxidant enzymes[superoxide dismutase(SOD),cata-lase(CAT),γ-glutamylcysteine synthase(γ-GCS)]activities and the Nrf2/NF-κB signaling pathway in the renal cortex and nucleus of the rats in each group were detected.Results Compared with the normal control group,the 24 h-UPro,T-CHOL,TG,HDL,LDL,sCr,and urea nitrogen increased,and ALB decreased(all P<0.05);subepithelial electron dense deposits in the glomeruli,diffuse fusion of the podocyte foot processes,and the width of the podocyte foot processes increased;the expression level and abnormal distribution of Podocin decreased,the expression level of Desmin was up-reg-ulated;the MDA,8-iso-PG,and 8-OHDG levels all increased in the renal cortex(all P<0.05),and the activities of SOD,CAT,and γ-GCS decreased(all P<0.05);Nrf2 was down-regulated,whereas NF-κB p65 and p-NF-κB p65(Ser536)were up-regulated in the renal cortex and nucleus in the model group(all P<0.05).Compared with the model group,the 24 h-UPro,T-CHOL,TG,HDL,LDL,and sCr levels all decreased,and the ALB increased(all P<0.05);the diffuse fusion of the podocyte foot processes was relieved,the podocyte foot processes width decreased,and the expres-sion and distribution of Podocin/Desmin tended to be normal;the MDA,8-iso-PG,and 8-OHDG levels decreased in the renal cortex(all P<0.05),and the activities of SOD,CAT,and γ-GCS increased(all P<0.05);Nrf2 was up-regulated,whereas NF-κB p65 and p-NF-κB p65(Ser536)were down-regulated in the renal cortex and nucleus of the tBHQ interven-tion group(all P<0.05).Conclusions The tBHQ inhibits renal injury and oxidative stress of MN rats,and can regulate the Nrf2/NF-κB signaling pathway in the renal cortex and nucleus.The tBHQ may activate Nrf2 and inhibit NF-κB activa-tion,thereby alleviating oxidative stress and renal injury in MN rats.关键词
特丁基对苯二酚/氧化应激/核因子E2相关因子2/核因子κB/肾脏损伤/膜性肾病Key words
tert-butylhydroquinone/oxidative stress/nuclear factor erythroid 2-related factor 2/nuclear factor-κB/renal injury/membranous nephropathy分类
医药卫生引用本文复制引用
吕道远,俞娅芬,储腊萍,蒋宏伟,周丽芳,彭俊琼,周喜连,郑燕列..tBHQ对膜性肾病大鼠肾组织损伤、氧化应激抑制及肾皮质和细胞核Nrf2/NF-κB信号通路调控作用[J].山东医药,2024,64(27):21-25,5.基金项目
无锡市卫生健康委科研项目(Q202308) （Q202308）
无锡市转化医学研究所项目(LCYJ202340) （LCYJ202340）
江南大学附属医院高层次专业技术人才科研启动项目(4542231GCRC). （4542231GCRC）
