摘要
目的观察右美托咪定预处理对盲肠结扎穿孔(CLP)模型小鼠脓毒症急性肾损伤的影响及其可能机制。方法将24只小鼠随机分为假手术组、模型组和实验组,每组8只。假手术组和模型组在造模前30 min预先腹腔注射等量生理盐水,实验组在造模前30 min预先腹腔注射右美托咪定100μg·kg(-1),假手术组仅暴露腹腔,不进行盲肠结扎穿孔,模型组和实验组随后予以盲肠结扎穿孔造模。24 h后用试剂盒方法测定小鼠血清肌酸酐、尿素氮、丙二醛及超氧化物歧化酶,用苏木精-伊红(HE)染色法观察肾组织病理形态学改变,用蛋白免疫印迹法测定肾组织核转录因子E2相关因子2(Nrf2)/血红素加氧酶(HO)-1信号通路蛋白表达。结果实验组血清肌酸酐、尿素氮、丙二醛和超氧化物歧化酶水平分别为(2.58±0.99)μmol·L(-1),(15.38±3.76)mmol·L(-1),(8.01±0.31)nmol·mL(-1),(155.11±10.98)U·mL(-1),模型组分别为(6.74±0.14)μmol·L(-1),(29.81±4.29)mmol·L(-1),(12.51±1.29)nmol·mL(-1),(119.52±9.95)U·mL(-1),差异均有统计学意义(均P<0.05)。实验组Nrf2和HO-1分别为1.19±0.15,1.00±0.10,模型组分别为0.36±0.13,0.40±0.06,差异均有统计学意义(均P<0.01)。结论右美托咪定预处理能减轻脓毒症引起的肾组织急性损伤,这种作用可能是通过激活Nrf2/HO-1途径抑制细胞氧化应激而产生的。
Objective To observe the effect of dexmedetomidine pretreatment on septic acute kidney injury in cecal ligation and puncture( CLP) model mice and its possible mechanism. Methods Twenty-four mice were randomly divided into sham group,model group and test group,with 8 mice in each group. In sham group and model group,the same amount of normal saline was intraperitoneally injected 30 min before modeling. In test group,dexmedetomidine 100 μg·kg(-1) was intraperitoneally injected 30 min before modeling. The sham group only exposed abdominal cavity,without cecal ligation and perforation,the model group and test group were subsequently cecal ligation and perforation. After 24 h,serum creatinine,urea nitrogen, malondialdehyde and superoxide dismutase( SOD) were measured by kit method. Histopathological changes of renal tissue were observed with hematoxylin-eosin( HE) staining. The expression of Nrf2/HO-1 signaling pathway in renal tissue was measured by Western blot method. Results The levels of serum creatinine,urea nitrogen,malondialdehyde and superoxide dismutase in test group were( 2. 58 ± 0. 99) μmol·L^-1,( 15. 38 ± 3. 76) mmol·L^-1,( 8. 01 ± 0. 31) nmol·mL^-1,( 155. 11 ± 10. 98) U·mL^-1,all had significant difference with those in model group,which were( 6. 74 ± 0. 14) μmol · L^-1,( 29. 81 ± 4. 29) mmol · L^-1,( 12. 51 ± 1. 29) nmol · mL^-1,( 119. 52 ± 9. 95) U·mL^-1( all P〈0. 05). The Nrf2 and HO-1 in test group were 1. 19 ± 0. 15 and 1. 00 ± 0. 10,had significant difference with those in model group,which were 0. 36 ± 0. 13 and 0. 40 ± 0. 06( P〈0. 01).Conclusion Dexmedetomidine pretreatment can reduce acute renal injury induced by sepsis. This effect may be caused by activation of Nrf2/HO-1 pathway to inhibit oxidative stress in cells.
作者
吴伟芳
吴奕隆
谭双羽
陈志锋
林艺延
王洪林
王鹤
陈晓乐
张南文
WU Wei-fang;WU Yi-long;TAN Shuang-yu;CHEN Zhi-feng;LIN Yi-yan;WANG Hong-lin;WANG He;CHEN Xiao-le;ZHANG Nan-wen(Department of Anesthesia,Fuzhou Children's Hospital of Fujian Province,Fuzhou 350005,China;a.The First Clinical College,b.School of Pharmacy,School of Clinical Medical,Fujian Medical University,Fuzhou 350122,China;School of Integrative Medicine,Fujian University of Traditional Chinese,Fuzhou 350122,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2018年第18期2167-2170,共4页
The Chinese Journal of Clinical Pharmacology
基金
福建省卫生计生中青年骨干人才培养基金资助项目(2018-ZQN-64)
福建省卫生计生青年科研课题基金资助项目(2017-1-69)
福建医科大学大学生创新创业训练计划基金资助项目(201810392028
C18015)