白藜芦醇调节NLRP3炎性小体改善力竭运动大鼠肾组织炎症损伤  

Resveratrol improves renal inflammatory injury in exhaustive exercise rats by regulating NOD-like receptor protein 3 inflammasome

作　　者：李方 曹建民[2] 翟鹏飞[1] 王建设[1] 洪达[1] LI Fang;CAO Jianmin;ZHAI Pengfei;WANG Jianshe;HONG Da(Physical Education College,Henan Normal University,Xinxiang,Henan Province,453007;Sport Science College,Beijing Sport University,Beijing,100084,China)

机构地区：[1]河南师范大学体育学院,河南新乡453007 [2]北京体育大学运动人体科学学院,北京100084

出　　处：《陆军军医大学学报》2022年第12期1229-1236,共8页Journal of Army Medical University

基　　金：河南省重点研发与推广专项(科技攻关)项目(212102310261)。

摘　　要：目的 探讨白藜芦醇通过调节NOD样受体蛋白3(NOD-like receptor protein 3,NLRP3)炎性小体对力竭运动大鼠肾组织炎症损伤的改善作用。方法 将36只SD雄性大鼠按随机数字表法分为对照组(Con组,n=8)、白藜芦醇组(Rsv组,n=8)、力竭运动组(Ex组,n=10)和力竭运动+白藜芦醇组(Ex+Rsv组,n=10)。Ex组和Ex+Rsv组进行4周力竭跑台运动。Rsv组和Ex+Rsv组每天灌胃白藜芦醇,剂量为50 mg/kg。最后1次运动24 h后取材,分别取血、尿和肾组织以备检测,全自动分析仪检测血清肌酐(serum creatinine, Scr)、尿素氮(blood urea nitrogen, BUN)水平;ELISA检测尿中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinaseassociated lipocalin, NGAL)和肾损伤分子-1 (kidney injury molecule-1,KIM-1)以及肾组织IL-1β、IL-18、TNF-α、IL-6水平;HE染色观察肾组织形态结构变化;Western blot检测肾组织NLRP3、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein, ASC)和cleaved caspase-1、IL-1β和IL-18蛋白表达;免疫荧光双染观察NLRP3和ASC在肾小管的共定位。结果 力竭运动组大鼠血清指标Scr及BUN、尿液指标KIM-1和NGAL水平均比对照组显著升高(P<0.01),肾组织HE染色显示存在肾组织损伤;力竭运动组大鼠肾组织NLRP3、ASC、cleaved caspase-1、IL-1β和IL-18蛋白表达均显著升高(P<0.01);白藜芦醇补充显著降低了力竭运动大鼠肾组织NLRP3炎性小体蛋白表达(P<0.05),改善其肾组织形态,降低肾组织炎症因子浓度(P<0.05)。结论 白藜芦醇可有效改善力竭运动大鼠肾组织炎症损伤,其机制可能与白藜芦醇抑制大鼠肾脏NLRP3炎性小体的过度激活有关。Objective To explore the ameliorative effects of resveratrol on renal inflammation in rats after exhaustive exercise by regulating NOD-like receptor protein 3(NLRP3) inflammasome. Methods Thirty-six male SD rats were randomly divided into 4 groups: control group(Con, n=8), resveratrol group(Rsv, n=8), exhaustive exercise group(Ex, n=10), and exhaustive exercise+resveratrol group(Ex+Rsv, n=10), and the rats in the Ex and Ex+Rsv groups underwent 4 weeks of exhaustive treadmill exercise. The Rsv and Ex+Rsv groups were given resveratrol intragastrically at a dose of 50 mg/kg per day. The serum and urine samples as well as renal tissues of rats were collected in 24 h after the last training. The serum creatinine(Scr) and blood urea nitrogen(BUN) levels were detected by automatic analyzer;ELISA was used to determine the urine neutrophil gelatinase-associated lipocalin(NGAL), kidney injury molecule-1(KIM-1) and the contents of IL-1β, IL-18, TNF-α and IL-6 in renal tissues;The protein expression of NLRP3, apoptosis-associated speck-like protein(ASC), cleaved caspase-1, IL-1β and IL-18 were measured by Western blotting. In addition, the morphological and structural changes of renal tissue were observed with HE staining, and immunofluorescence staining was also performed to observe the co-localization of NLRP3 and ASC. Results The levels of Scr, BUN, NGAL and KIM-1 were significantly higer in the Ex group than the Con group(P<0.01). HE staining showed that renal injury was observed in the rats of Ex group, and the protein expression levels of NLRP3, ASC, cleaved caspase-1, IL-1β and IL-18 were all remarkably increased(P<0.01). However, resveratrol supplementation notably down-regulated the protein expression of NLRP3 inflammasome(P<0.05) and reduced the contents of inflammatory factors in renal tissues(P<0.05), and ameliorated pathological changes of renal tissues. Conclusions Resveratrol can effectively alleviate the inflammatory damage of renal tissue in rats after exhaustive exercise, and its mechanism may be relate

关 键 词：白藜芦醇 NLRP3炎性小体 力竭运动 炎症反应 

分 类 号：R285.5[医药卫生—中药学] R692.3[医药卫生—中医学] R873.01