白藜芦醇调控SIRT1/PGC-1α通路减轻IgA肾损伤  

Resveratrol reduces IgA kidney injury through regulating SIRT1/PGC-1 alpha pathway

作　　者：任园伟 何银银[2] REN Yuanwei;HE Yinyin(Zhejiang Chinese Medical University,Hangzhou 310000,Zhejiang,China;Dept.of Critical Care Medicine,Shaoxing Hospital of Traditional Chinese Medicine,Shaoxing 312000,Zhejiang,China)

机构地区：[1]浙江中医药大学,浙江杭州310000 [2]绍兴市中医院重症医学科,浙江绍兴312000

出　　处：《武汉大学学报（医学版）》2023年第2期132-137,173,共7页Medical Journal of Wuhan University

基　　金：浙江省中医药科技计划项目(编号:2022ZB362)。

摘　　要：目的:探讨白藜芦醇(RSV)对免疫球蛋白A(IgA)肾损伤的影响及其作用机制。方法:将60只SD大鼠随机分为对照组(Control组)、模型组(Model组)、白藜芦醇组[RSV组,100 mg/(kg·d)]、沉默信息调节因子1(SIRT1)抑制剂组(EX-527组,10 mg/kg)、RSV+EX-527组[100 mg/(kg·d)RSV和10 mg/kg EX-527],每组12只。除Control组外,其他组均按照BSA+LPS+CCl4方法构建IgA肾病模型,造模成功后,进行药物处理,Control组和Model组灌胃等量的生理盐水,每天1次,持续8周。收集24 h尿,通过邻苯三酚红钼法检测尿蛋白(Upr)含量;自动生化分析仪测量血清中血肌酐(Scr)、血尿素氮(BUN)的含量;HE染色检测大鼠肾组织病理变化;超氧化物歧化酶(SOD)、丙二醛(MDA)检测试剂盒检测大鼠肾组织中SOD、MDA水平;ELISA法检测大鼠肾组织匀浆中白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)水平;TUNEL染色检测大鼠肾组织细胞凋亡;Western Blot检测SIRT1、过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)蛋白表达。结果:与Control组比较,Model组大鼠肾组织中肾小管结构破坏,有大量炎性细胞浸润,Upr、Scr、BUN含量、MDA、IL-6、TNF-α水平及细胞凋亡率显著升高,SOD水平及SIRT1、PGC-1α蛋白表达水平显著降低(P<0.05);与Model组比较,RSV组大鼠肾小管结构破坏及炎性细胞浸润症状明显减轻,Upr、Scr、BUN含量、MDA、IL-6、TNF-α水平及细胞凋亡率显著降低,SOD水平及SIRT1、PGC-1α蛋白表达水平显著升高(P<0.05),而EX-527组对应指标与上述趋势相反(P<0.05);与RSV组比较,RSV+EX-527组大鼠肾小管结构破坏,炎性细胞浸润明显可见,Upr、Scr、BUN含量、MDA、IL-6、TNF-α水平及细胞凋亡率显著升高,SOD水平及SIRT1、PGC-1α蛋白表达水平显著降低(P<0.05)。结论:RSV可能通过激活SIRT1/PGC-1α通路抑制氧化应激、炎症反应及细胞凋亡来发挥对IgA肾损伤的保护作用。Objective:To investigate the effect of resveratrol(RSV)on immunoglobulin A(IgA)kidney injury and its mechanism.Methods:Sixty SD rats were randomly divided into Control group,Model group,resveratrol group(RSV group,100 mg/[kg·d]),SIRT1 inhibitor group(EX-527 group,10 mg/kg),and RSV+EX-527 group(100 mg/[kg·d]RSV and 10 mg/kg EX-527),with 12 rats per group.Except for the Control group,all other groups constructed IgA nephropathy models according to the BSA+LPS+CCl4 method.After the models were successfully established,they were treated with drugs,the Control group and the Model group were given the same amount of normal saline,once a day for 8 weeks.The 24-h urine were collected,pyrogallol red molybdenum method was used to detect the content of urine protein(Upr);automatic biochemical analyzer was used to measure the contents of serum creatinine(Scr)and blood urea nitrogen(BUN);HE staining was used to detect pathological changes in rat kidney tissue;superoxide dismutase(SOD)and malondialdehyde(MDA)detection kits were used to detect the levels of SOD and MDA in rat kidney tissue;ELISA method was used to detect the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat kidney tissue homogenate;TUNEL staining was used to detect cell apoptosis in rat kidney tissue;Western Blot was used to detect the protein expression of silent information regulator 1(SIRT1)and peroxisome proliferator activated receptorγcoactivator-1α(PGC-1α).Results:Compared with that respectively in the Control group,the renal tubule structure in the kidney tissue of Model group was broken,and there was a large amount of inflammatory cell infiltration,the Upr,Scr,and BUN contents,the MDA,IL-6,and TNF-αlevels,and cell apoptosis rate were significantly increased,the SOD level and SIRT1 and PGC-1αprotein expression levels were significantly reduced(P<0.05);compared with that respectively in the Model group,the renal tubular structure was injured and inflammatory cell infiltration symptoms were significantly reduced in the RSV grou

关 键 词：白藜芦醇 免疫球蛋白A肾损伤 沉默信息调节因子1 过氧化物酶体增殖物激活受体γ辅激活因子1α 氧化应激 炎症 

分 类 号：R692.3[医药卫生—泌尿科学]