摘要
目的探讨右美托咪定对脓毒症急性肾损伤大鼠肾组织的影响及机制。方法采用盲肠结扎穿孔法建立大鼠脓毒症模型。按随机数字表法将大鼠随机分为假手术组、假手术干预组、模型组、模型干预组,每组10只。模型组和模型干预组建立脓毒症模型,假手术组和假手术干预组仅开腹不作处理。假手术干预组和模型干预组于制模前1 h经尾静脉泵入右美托咪定,泵注速度为5μg·kg^(-1)·h^(-1),假手术组和模型组制模前1 h泵入等量生理盐水。用酶联免疫吸附(ELISA)法分别检测血清肾损伤分子-1(KIM-1)及中性粒细胞明胶酶相关脂质运载蛋白(NGAL)表达量;用苏木精-伊红(HE)染色后观察肾组织病理学变化,并行肾小管损伤评分;用蛋白质印迹法检测各组大鼠肾组织密封蛋白-5(Claudin-5)和闭锁蛋白-1(ZO-1)蛋白表达。结果术后24 h时,假手术组、假手术干预组、模型组、模型干预组血清NGAL表达量分别为(11.36±1.78),(10.84±1.50),(27.04±1.99)和(12.61±2.97)ng·mL^(-1);这4组术后KIM-1表达量分别为(69.62±7.94),(76.26±5.57),(162.00±12.58)和(89.43±11.45)pg·mL^(-1);这4组术后肾小管损伤评分分别为(0.42±0.20),(0.39±0.24),(3.52±0.34)和(2.08±0.38)分;这4组术后24 h,Claudin-5蛋白相对表达水平分别为0.23±0.02,0.22±0.02,0.15±0.01和0.17±0.02;这4组术后24 h,ZO-1蛋白相对表达水平分别为0.29±0.02,0.29±0.02,0.13±0.02和0.16±0.02;以上指标,模型组与假手术组比较,模型干预组与模型组比较,差异均有统计学意义(均P<0.01).结论右美托咪定可通过上调Claudin-5和ZO-1的表达,减轻大鼠脓毒症急性肾损伤,从而起到一定保护作用。
Objective To investigate the effect and mechanism of dexmedetomidine on renal tissue of septic acute kidney injury rats.Methods Rat sepsis model was established by cecal ligation and puncture.Rats were randomly divided into sham operation group,sham operation intervention group,model group and model intervention group according to the random number table method,with 10 rats in each group.Model group and model intervention group were established sepsis model,sham operation group and sham operation intervention group only laparotomy without treatment.In the sham operation intervention group and the model intervention group,dexmedetomidine was pumped through the tail vein 1 h before modeling,and the pumping rate was 5μg·kg^(-1)·h^(-1).In the sham operation group and the model group,the same amount of normal saline was pumped 1 h before modeling.The expression levels of serum kidney injury molecule-1(KIM-1)and neutrophil gelatinase-associated lipocalin(NGAL)were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue were observed after hematoxylin-eosin(HE)staining,and the renal tubular injury score was performed.The expressions of Claudin-5 and zonula occludens-1(ZO-1)in renal tissues of rats in each group were detected by immunohistochemistry and Western blotting.Results At 24 h after operation,the serum NGAL expressions in sham operation group,sham operation intervention group,model group and model intervention group were(11.36±1.78),(10.84±1.50),(27.04±1.99)and(12.61±2.97)ng·mL^(-1),respectively.The postoperative KIM-1expressions in the four groups were(69.62±7.94),(76.26±5.57),(162.00±12.58)and(89.43±11.45)pg·mL^(-1),respectively.The postoperative renal tubular injury scores of the four groups were(0.42±0.20),(0.39±0.24),(3.52±0.34)and(2.08±0.38)points,respectively.At 24 h after operation,the relative expression levels of Claudin-5 protein in the four groups were 0.23±0.02,0.22±0.02,0.15±0.01 and0.17±0.02,respectively.At 24 h after operation,the relativ
作者
周文杰
张楠
杨海荣
刘勤富
马希刚
ZHOU Wen-jie;ZHANG Nan;YANG Hai-rong;LIU Qin-fu;MA Xi-gang(Department of Intensive Care Unit,General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China;Department of Operating Room,General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China;Department of Intensive Care Unit,People's Hospital of Ningxia Hui Autonomous Region,Yinchuan 750021,Ningxia Hui Autonomous Region,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第13期1481-1485,共5页
The Chinese Journal of Clinical Pharmacology
基金
宁夏自然科学基金资助项目(2019AAC03243)
宁夏回族自治区重点研发计划基金资助项目(2021BEG03094)
宁夏青年科技人才托举工程基金资助项目(TJGC20190099)
宁夏医科大学总医院新冠肺炎疫情防控应急基金资助项目(XE202018)。
