右美托咪定对肝缺血再灌注诱发大鼠肾损伤的影响

Effect of dexmedetomidine on kidney injury induced by liver ischemia-reperfusion in rats

目的评价右美托咪定对肝缺血再灌注诱发大鼠肾损伤的影响。方法清洁级健康雄性SD大鼠24只，体重220—250g，8—10周龄，采用随机数字表法分为3组（n=8）：假手术组（S组）、肝缺血再灌注组（I／R组）和右美托咪定组（D组）。I／R组采用夹闭门静脉、肝固有动脉、肝上下腔静脉和肝下下腔静脉后行肝脏灌注40min制备肝缺血再灌注损伤模型。D组于切皮前30min时腹腔注射右美托咪定100μg／kg；S组和I／R组腹腔注射等容量生理盐水。再灌注6h时，经肝下下腔静脉采集血样后处死大鼠，取。肾组织，采用全自动血生化仪检测血清BUN和Cr的浓度，采用ELISA法检测血清TNF-α和IL-10的浓度；光镜下观察肾组织病理学结果，采用硫代巴比妥酸法测定MDA含量，采用黄嘌呤氧化酶法测定SOD活性，采用免疫组化法检测肾组织活化的caspase-3的表达，采用TUNEL法检测细胞凋亡情况，计算细胞凋亡率。结果与S组比较，I／R组和D组血清BUN、Cr和TNF—α的浓度升高，IL-10的浓度降低，肾组织MDA含量和细胞凋亡率升高，SOD活性降低，活化的caspase-3表达上调（P〈0．05）；与I／R组比较，D组血清BUN、Cr和TNF-α的浓度降低，IL-10浓度升高，肾组织MDA含量和细胞凋亡率降低，SOD活性升高，活化的caspase-3表达下调（P〈0．05），肾组织病理学损伤减轻。结论右美托咪定可减轻肝缺血再灌注诱发大鼠肾损伤，其机制可能与抑制炎性反应、脂质过氧化反应和细胞凋亡有关。

Objective To evaluate the effect of dexmedetomidine on kidney injury induced by liver ischemia-reperfusion （I/R） in rats. Methods Twenty-four healthy male Sprague-Dawley rats, weighing 220-250 g, aged 8-10 weeks, were randomly divided into 3 groups （n= 8 each） using a random number table： sham operation group （group S） ; liver I/R group （group I/R） ; dexmedetomidine group （group D）. In group I/R, liver I/R model was established by clamping the portal vein, hepatic artery, supra- and infra-hepatic vena cava for 40 rain, followed by 6 h of reperfusion in anesthetized rats. In group D, dexme- detomidine 100 μg/kg was injected intraperitoneally at 30 min before skin incision. The equal volume of normal saline was given instead of dexmedetomidine in S and I/R groups. At 6 h of reperfusion, blood sam- ples were collected from the infra-hepatic vena cava for determination of blood urea nitrogen （BUN） and creatinine （Cr） concentrations （ by automatic biochemical analyzer） and tumor necrosis factor-alpha （ TNF- α） and interleukin-10 （IL-10） concentrations in serum （by enzyme-linked immunosorbent assay）. After blood sampling, the rats were sacrificed, and kidneys were harvested for examination of histopathological changes （with light microscope） and for determination of malondialdehyde （MDA） content （using thiobarbituric acid method） and superoxide dismutase （SOD） activity （by xanthine oxidase method）, expression of activated caspase-3 （ by immuno-histochemistry） , and apoptotic cells （ using TUNEL）. Apoptotic rate was calculated. Results Compared with group S, the serum BUN, Cr and TNF-α concentrations were sig- nificantly increased, the concentration of serum IL-10 was decreased, the M DA content and apoptotic rate were increased, the SOD activity was decreased, and the expression of activated caspase-3 was up-regulated in I/R and D groups （ P〈0.05）. Compared with group I/R, the serum BUN, Cr and TNF-α concentrations were significantly decreased, the concentration of serum IL-10 was increased, MDA content and apoptotic rate were increased, the SOD activity was decreased, the expression of activated caspase-3 was down-regulated （P〈0.05） , and the histopathological changes of renal tissues were attenuated in group D. Conclusion Dexmedetomidine can reduce kidney injury induced by liver I/R in rats, and the mechanism is probably related to inhibition of inflammatory responses, lipid peroxidation and cell apoptosis.