舒芬太尼和吗啡对顺铂致大鼠急性肾损伤的影响

Effects of sufentanil and morphine on cisplatin-induced acute kidney injury in rats

目的 评价舒芬太尼和吗啡对顺铂致大鼠急性肾损伤的影响.方法 健康雄性SD大鼠32只,8～10周龄,体重220～280 g,采用随机数字表法分为4组（n=8）：对照组（C组）、顺铂（Cis组）、舒芬太尼组（S组）和吗啡组（M组）.Cis组腹腔注射顺铂16 mg/kg;S组腹腔注射顺铂16mg/kg后,经5 min尾静脉注射舒芬太尼2μg/kg,连续注射3 d;M组腹腔注射顺铂16 mg/kg后,经5min尾静脉注射吗啡2 mg/kg,连续注射3 d;C组注射等容量生理盐水.第3天给药结束后,采集眼眶静脉血样,检测血清BUN和Cr的浓度,然后处死大鼠,取左侧肾组织,行碘酸-Schiff＇s染色,光镜下观察病理学结果,并行肾小管损伤评分;采用ELISA法检测肾组织TNF-α、IL-1β和IL-6的含量,采用Western blot法检测肾组织X连锁凋亡抑制蛋白（XIAP）、生存素和caspase-3的表达水平.结果 与C组比较,Cis组、S组和M组血清BUN、Cr的浓度和肾小管损伤评分升高,肾组织TNF-α、 IL-1β和IL-6的含量升高,肾组织XIAP和生存素的表达下调,caspase-3表达上调（P＜0.05）;与Cis组比较,S组和M组血清BUN、Cr的浓度和肾小管损伤评分降低,肾组织TNF-α、IL-1β和IL-6的含量降低,肾组织XIAP和生存素的表达上调,caspase-3表达下调（P＜0.05）.S组和M组间上述各指标比较差异无统计学意义（P＞0.05）.结论 舒芬太尼和吗啡均可减轻顺铂致大鼠急性肾损伤,且2种药物作用相当,其机制可能与抑制炎性反应和细胞凋亡有关.

Objective To evaluate the effects of sufentanil and morphine on cisplatin-induced acute kidney injury in rats.Methods Thirty-two healthy Sprague-Dawley rats, aged 8-10 weeks, weighing 220-280 g, were randomly divided into 4 groups （n =8 each） using a random number table： control group （group C）;cisplatin group （group Cis）;sufentanil group （group S）;morphine group （group M）.Cisplatin 16 mg/kg was injected intraperitoneally in group Cis.In group S, cisplatin 16 mg/kg was injected intraperitoneally, followed by injection of sufentanil 2 μg/kg over 5 min via the caudal vein for 3 consecutive days.In group M, cisplatin 16 mg/kg was injected intraperitoneally, followed by injection of morphine 2 μg/kg over 5 min via the caudal vein for 3 consecutive days.The equal volume of normal saline was given in group C.After the end of administration on 3rd day, blood samples were collected from the orbital venous plexus for measurement of serum blood urea nitrogen （BUN） and creatinine （Cr） concentrations.The animals were then sacrificed, and the left kidney specimens were obtained for examination of the pathological changes （under the light microscope） and for determination of the tumor necrosis factor-alpha （TNF-α） , interleukin-1 beta （IL-1β） and interleukin-6 （IL-6） concentrations （by enzyme-linked immunosorbent assay） , and expression of X-linked inhibitor of apoptosis protein （XIAP） , suvivin and caspase-3 （by Western blot）.Periodic acid-Schiff＇s staining was used to evaluate the pathological changes of the renal tubule.Results Compared with group C, the serum BUN, Cr concentrations and renal tubule injury score were significantly increased, the contents of TNF-α, IL-1β and IL-6 were increased, the expression of XIAP and suvivin was down-regulated, and the expression of caspase-3 was up-regulated in Cis,S and M groups （P〈0.05）.Compared with group Cis, the serum BUN and Cr concentrations and renal tubule injury score were significantly decreased, the contents of TNF-α, IL-1β and IL-6 were decreased, the expression of XIAP and suvivin was up-regulated, and the expression of caspase-3 was down-regulated in S and M groups （P〈0.05）.There were no significant differences in the indexes mentioned above between group S and group M （P〉0.05）.Conclusion Both sufentanil and morphine can reduce cisplatin-induced acute kidney injury in rats with similar efficacy, and the mechanism may be related to the inhibition of the inflammatory responses and cell apoptosis.