右美托咪定对内毒素血症大鼠急性肾损伤的影响

Effect of dexmedetomidine on acute kidney injury in endotoxemic rats

目的 探讨右美托咪定对内毒素血症大鼠急性肾损伤的影响.方法 健康雄性清洁级SD大鼠30只,4～6月龄,体重180 ～ 220 g,采用随机数字表法分为3组（n=10）：对照组（C组）、脂多糖（LPS）组（L组）和右美托咪定组（D组）.L组静脉注射LPS 5 mg/kg制备内毒素血症模型.D组静脉注射LPS 5 mg/kg后,静脉注射右美托咪定负荷量7μg/kg,15 min后以5μg· kg-1·h-1的速率静脉输注6 h,L组和C组给予等容量生理盐水.LPS给药结束后6h时取股静脉血样,检测血清Cr、BUN、TNF-α和IL-6的浓度.LPS给药结束后24 h时处死动物,取肾组织,观察病理学结果,采用Western blot法测定紧密连接蛋白ZO-1和occludin的表达水平.结果 与C组比较,L组和D组血清Cr、BUN、TNF-α和IL-6的浓度升高,肾组织ZO-1和occludin的表达下调（P＜0.05）;与L组比较,D组血清Cr、BUN、TNF-α和IL-6的浓度降低,肾组织ZO-1和occludin的表达上调（P＜0.05）.D组肾组织病理学损伤较L组减轻.结论 右美托咪定可减轻内毒素血症大鼠急性肾损伤.

Objective To investigate the effect of dexmedetomidine on acute kidney injury in endotoxemic rats.Methods Thirty adult male Sprague-Dawley rats,aged 4-6 months,weighing 180-220 g,were randomly divided into 3 groups （n =10 each） using a random number table：control group （group C）,lipopolysaccharide group （group L）,and dexmedetomidine （group D）.Lipopolysaccharide （LPS） 5 mg/kg was injected slowly into the femoral vein to establish the model of endotoxemic in rats anesthetized with chloral hydrate.In group D,after LPS injection,a loading dose of dexmedetomidine 7 μg/kg was injected intravenously,and 15 min later dexmedetomidine was infused for 6 h at 5 μg · kg-1 · h-1,while the equal volume of normal saline was given in L and C groups.At 6 h after the end of LPS administration,blood samples were collected from the femoral vein for determination of serum creatinine （Cr）,blood urea nitrogen （BUN）,tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） concentrations.At 24 h after the end of LPS administration,the animals were sacrificed and kidneys were removed for microscopic examination and for determination of the expression of tight junction proteins ZO-1 and occludin in renal tissues by Western blot.Results Compared with group C,the serum Cr,BUN,TNF-α and IL-6 concentrations were significantly increased,and the expression of ZO-1 and occluding was down-regulated in L and D groups.Compared with group L,the serum Cr,BUN,TNF-α and IL-6 concentrations were significantly decreased,the expression of ZO-1 and occluding was up-regulated,and the pathological changes of kidneys were mitigated in D group.Conclusion Dexmedetomidine can alleviate acute kidney injury in endotoxemic rats.