首页|NLRP3蛋白介导乌司他丁减轻肢体缺血再灌注损伤

NLRP3蛋白介导乌司他丁减轻肢体缺血再灌注损伤

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目的 观察核因子-κB(nuclear factor-κB,NF-κB)/NOD 样受体家族 3(NOD-like receptors family pyrin domain containing 3,NLRP3)通路在乌司他丁(ulinastatin,UTI)预处理肢体缺血再灌注损伤中的作用情况.方法 采用随机数字表法将21只SD大鼠分入对照组、模型组、实验组,每组7只.对实验组采取经尾静脉注射UTI干预,另两组经尾静脉行生理盐水干预,经过10min,于一侧股部切口,借助动脉夹对股动脉行夹闭处理,同时借助橡皮筋在恒定张力下对侧支循环进行环扎阻断处理.3h后去除阻断,并再灌注2h,取大鼠血清测量肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、乳酸脱氢酶(lactate dehydrogenase,LDH)、白细胞介素(interleukin,IL)-6、肌酸激酶(creatine kinase,CK)、IL-18;取部分腓肠肌-80℃冻存,PCR、Western blot法检测NF-κB/NLRP3.另取一部分腓肠肌存储于多聚甲醛内,借助光镜查看骨骼肌形态,切取小部分腓肠肌测定湿干比.结果 与对照组比较,模型组湿干比、LDH、CK、IL-6、IL-18、TNF-α、NF-κB、NLRP3明显升高,差异有统计学意义(P<0.05);与模型组比较,实验组湿干比、LDH、CK、IL-6、IL-18、TNF-α、NF-κB、NLRP3明显降低,差异有统计学意义(P<0.05).结论 UTI可通过NF-KB/NLRP3通路降低细胞炎症反应,从而实现对大鼠肢体缺血再灌注损伤的保护作用.
Ulinastatin reduces ischemia-reperfusion injury mediated by NLRP3 in skeletal muscle
Objective To investigate the role of nuclear factor-κB(NF-κB)/NOD-like receptors family pyrin domain containing 3(NLRP3)pathway in limb ischemia-reperfusion injury(IRI)pretreated with ulinastatin(UTI).Methods Twenty-one SD rats were randomly divided into Sham group,IRI group,UTI group.In UTI group,ulinastatin was injected after anesthesia.After 10 minutes,the animal model was established by claming the femoral artery and ligaturing collateral circulation.After 3h of ischemia,the clamp and tourniquet were removed and the rats underwent 2h of reperfusion.In the other groups,the homologous saline was also injected in the same time.Plasma concentrations of lactate dehydrogenase(LDH)and creatine kinase(CK),interleukin(IL)-6,IL-18,tumor necrosis factor-α(TNF-α)were measured.The gastrocnemius muscle was harvested and immediately stored at-80℃.NF-κB and NLRP3 were detected by Western blot and PCR.The other section muscle was stored in triformol for HE staining.The wet/dry was also immediately detecting.Results The level of wet/dry,LDH,CK,IL-6,IL-18,TNF-α,NF-κB,NLRP3 IRI were higher than those in Sham group(P<0.05).The level of wet/dry,LDH,CK,IL-6,IL-18,TNF-α,NF-κB,NLRP3 IRI were significantly lower than those in IRI group(P<0.05).Conclusion Ulinastatin can reduce the cellular inflammatory response through the NF-κB/NLRP3 pathway,thereby achieving a protective effect on limb IRI in rats.

Ischemia-reperfusion injuryInflammatory responseNF-κB/NLRP3 pathwayUlinastatin

齐良、袁培根、陈亚兰、刘雪娇

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温州医科大学附属第一医院麻醉科,浙江温州 325000

缺血/再灌注损伤 炎症反应 NF-κB/NLRP3通路 乌司他丁

浙江省温州市科技计划项目

Y2020777

2024

中国现代医生
中国医学科学院

中国现代医生

影响因子:1.571
ISSN:1673-9701
年,卷(期):2024.62(26)