摘要
目的:探讨右美托咪定(dexmedetomidine,DEX)对盲肠结扎穿孔(cecal ligation perforation,CLP)诱导的大鼠脓毒症急性肾损伤(acute kidney injury,AKI)的保护作用及其机制。方法:将60只雄性SD大鼠随机分为4组:假手术(Sham)组、Sham+DEX组、CLP组和CLP+DEX组,每组各15只。CLP法制备大鼠脓毒症AKI模型,各组分别于术后6、12和24 h处死5只大鼠收集血清和肾脏组织。生化分析仪检测血清肌酐(serum creatinine,SCr)和血尿素氮(blood urea nitrogen,BUN)水平;ELISA法检测血清中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)和肾损伤分子1(kidney injury molecule-1,Kim-1)的水平;HE染色观察大鼠肾组织病理改变;透射电镜下观察肾组织超微结构改变;免疫组化、Western blot和RT-qPCR检测肾组织NOD样受体蛋白3(NOD-like receptor protein 3,NLRP3)、caspase-1、白细胞介素1β(interleukin-1β,IL-1β)和IL-18的表达。结果:与Sham组相比,CLP组大鼠可见肾小管损伤的病理改变,且随着术后时间延长,肾小管损伤呈加重趋势,肾小管损伤评分、血清SCr、BUN、NGAL和Kim-1水平及肾组织中NLRP3、caspase-1、IL-1β和IL-18的表达均显著升高(P<0.01)。与CLP组相比,CLP+DEX组大鼠肾小管病理损伤程度减轻,血清SCr、BUN、NGAL和Kim-1水平及肾组织中NLRP3、caspase-1、IL-1β和IL-18的表达均显著下降(P<0.01)。结论:DEX通过抑制NLRP3炎症小体活化,从而减轻大鼠脓毒症急性肾损伤。
AIM:To investigate the protective effect and mechanism of dexmedetomidine(DEX)on septic acute kidney injury(AKI)induced by cecal ligation perforation(CLP)in rats.METHODS:Sixty male SD rats were randomly divided into 4 groups:sham operation(Sham)group,Sham+DEX group,CLP group and CLP+DEX group,each with 15 rats.The rat septic AKI model was prepared by CLP method,and 5 rats in each group were sacrificed at 6,12 and24 h after operation to collect serum and kidney tissue.Serum creatinine(SCr)and blood urea nitrogen(BUN)levels were detected by biochemical analyzer.Serum neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(Kim-1)levels were detected by ELISA.HE staining was used to observe the pathological changes of rat kidney tissue under light microscope.The ultrastructural changes of renal tissue were observed under transmission electron microscope.Immunohistochemistry,Western blot and RT-qPCR were used to detect renal tissue NOD-like receptor protein 3(NLRP3),caspase-1,interleukin 1β(IL-1β)and IL-18 expression.RESULTS:Compared with Sham group,the pathological changes of renal tubule injury were observed in CLP group,and the renal tubule injury was aggravated with the extension of postoperative time.The renal tubule injury score,serum levels of SCr,BUN,NGAL and Kim-1,and the expressions of NLRP3,caspase-1,IL-1βand IL-18 in renal tissue were significantly increased(P<0.01).Compared with CLP group,the pathological damage of renal tubules in CLP+DEX group was reduced,the levels of SCr,BUN,NGAL and Kim-1 in serum,and the expressions of NLRP3,caspase-1,IL-1βand IL-18 in renal tissues were significantly decreased(P<0.01).CONCLUSION:Dexmedetomidine alleviates acute kidney injury in sepsis rats by inhibiting the activation of NLRP3 inflammasome.
作者
周文杰
杨海荣
张楠
刘勤富
马希刚
ZHOU Wen-jie;YANG Hai-rong;ZHANG Nan;LIU Qin-fu;MA Xi-gang(Department of Intensive Care Unit,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Affiliated Autonomous Region People's Hospital of Ningxia Medical University,Yinchuan 750021,China;Department of Operating Room,General Hospital of Ningxia Medical University,Yinchuan 750004,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2021年第12期2219-2227,共9页
Chinese Journal of Pathophysiology
基金
宁夏自然科学基金项目(No.2019AAC03243)
宁夏回族自治区重点研发计划项目(No.2021BEG03094)
宁夏青年科技人才托举工程项目(No.TJGC20190099)
宁夏医科大学总医院新冠肺炎疫情防控应急项目(No.XE202018)。
