摘要
目的研究虎杖苷对脓毒血症肾损伤大鼠肾小球血管内皮保护作用及磷酸腺苷活化蛋白激酶(AMPK)和西罗莫司靶点(mTOR)在其过程中的活性。方法在大鼠尾静脉注射脂多糖建立脓毒血症模型。按照体重将大鼠随机分为4组:假手术组(实施麻醉、置管),模型组(实施麻醉、置管及脓毒血症),对照组(实施麻醉、置管、脓毒血症及应用0.9%NaCl复苏),实验组(实施麻醉、置管、脓毒血症及应用0.9%NaCl+虎杖苷10 kU·kg^(-1))。测定心率和肾功能的指标,用酶联免疫吸附法检测每组AMPK和mTOR蛋白活化情况。结果给药后6 h,实验组、对照组、模型组的心率(次/分)分别为88.21±17,102.36±12.83,118.04±16.51;这3组的尿素氮分别为(49.77±9.67),(77.92±12.01),(122.19±12.87)mg·dL^(-1),与对照组和模型组相比,差异均有统计学意义(均P<0.05)。实验组与模型组的AMPK分别为3.06±1.34,0.77±0.21;这2组的mTOR蛋白活性分别为2.48±1.12,3.95±1.02,与模型组比较,实验组差异均有统计学意义(均P<0.05)。结论虎杖苷能够对脓毒血症肾损伤肾小球血管内皮起保护作用,这可能通过AMPK途径抑制mTOR的活性,发挥其保护肾的作用。
Objective To investigate the protective effects of polydatin on performance of sepsis injury of renal glomerular vascular endothelial and the activity of adenosine monophosphate( AMP)-activated protein kinase( AMPK) and mammalian target protein( mTOR) in the process.Methods The sepsis model was established by injection of lipopolysaccharide through the tail vein of rats. The rats were divided into four groups: sham operated group( implementation of anesthesia,intubation),model group( anesthesia,intubation and sepsis),control group( anesthesia,intubation and application of saline resuscitation),experimental group( anesthesia,intubation and sepsis,saline combined with tiger polydatin 10 kU·kg^(-1)). The activity of AMPK and mTOR in each groups were detected by ELISA. Results After administration for 6 h,the heart rate( beat per minute) in experimental group,control group,model group were 88. 21 ± 17,102. 36 ± 12. 83,118. 04 ± 16. 51. The urea nitrogen( BUN) in the three groups were( 49. 77 ± 9. 67),( 77. 92 ± 12. 01),( 122. 19 ± 12. 87) mg·dL^(-1). Compared with the control and modelgroups,all of them in experimental group were statistically significant( all P 〈0. 05). The protein activeties of AMPK and mTOR in experimental group,model group were respectively 3. 06 ± 1. 34,0. 77 ± 0. 21; 2. 48 ± 1. 12,3. 95 ± 1. 02.Compared with model groups,all of them in experimental group were statistically significant( all P 〈0. 05).Conclusion Polydatin had protective effect on septic renal damage glomerular vascular endothelial,which might be correlated with its inhibition on mTOR activity through AMPK pathway.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2018年第3期297-299,311,共4页
The Chinese Journal of Clinical Pharmacology
基金
山东省自然科学基金青年基金资助项目(2014ZRB14193)
关键词
虎杖苷
脓毒血症
内皮细胞
磷酸腺苷活化蛋白激酶
西罗莫司靶点
polydatin
sepsis
endothelial glycocalyx layer
AMP- activated protein kinase
mammalian target of rapamycin