不同剂量羟考酮对大鼠肾缺血再灌注损伤的影响

Different doses of oxycodone on renal ischemia-reperfusion injury in rats

目的 评价不同剂量羟考酮对大鼠肾缺血再灌注损伤的影响.方法 健康成年雄性SD大鼠40只,体重220～ 300 g,10～13周龄,采用随机数字表法,将其分为5组（n=8）：假手术组（S组）、缺血再灌注组（I/R组）、低、中和高剂量羟考酮组（OL组、OM组和OH组）.采用切除右侧肾脏,并夹闭左侧肾动脉和肾静脉45 min恢复灌注3h的方法制备大鼠肾缺血再灌注损伤模型,S组仅切除右肾、分离左侧肾动脉、肾静脉和输尿管.OL组、OM组和OH组于缺血即刻分别静脉注射羟考酮2、4和6 mg/kg.于再灌注3h时经腹主动脉采集血样,采用脲酶法测定血清尿素氮（BUN）浓度,采用速率法测定血清肌酐（Cr）浓度.采集血样后处死大鼠,取左肾组织,采用ELISA法测定肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和白细胞介素-10（IL-10）的含量,采用黄嘌呤氧化酶法测定超氧化物歧化酶（SOD）活性,采用硫代巴比妥酸法测定丙二醛（MDA）含量.结果 与S组比较,其余4组血清BUN和Cr的浓度升高,肾组织TNF-α、IL-6、IL-8和MDA的含量升高,肾组织IL-10含量和SOD活性降低（P＜0.05）;与I/R组比较,OL组、OM组和OH组血清BUN和Cr的浓度降低,肾组织TNF-α、IL-6、IL-8和MDA的含量降低,肾组织IL-10含量和SOD活性升高（P＜0.05）;OL组、OM组和OH组血清BUN和Cr的浓度、肾组织TNF-α、IL-6、IL-8和MDA的含量依次降低,肾组织IL-10含量和SOD活性依次升高（P＜0.05）.结论 羟考酮2、4和6 mg/kg可减轻大鼠肾缺血再灌注损伤,且呈剂量依赖性,其机制可能与抑制炎性反应和氧化应激反应有关.

Objective To evaluate the effects of different doses of oxycodone on renal ischemiareperfusion （I/R） injury in rats.Methods Forty adult male Sprague-Dawley rats, weighing 220-300 g, aged 10-13 weeks, were randomly divided into 5 groups （n =8 each） using a random number table： sham operation group （group S）, group I/R, and low, medium and high doses of oxycodone groups （OL, OM and OH groups）.After the rats underwent right nephrectomy, the renal I/R was induced by occlusion of the left renal artery and vein for 45 min with atraumatic microclips followed by 3 h reperfusion in I/R, OL, OM and OH groups.In group S, right nephrectomy was performed, and the left renal artery, vein and ureter were isolated without occluding blood flow.In OL, OM and OH groups, oxycodoue 2, 4, and 6 mg/kg were infused intravenously, respectively, immediately after onset of ischemia.At 3 h of reperfusion, blood samples were taken from the abdominal aorta to determine the concentrations of serum blood urea nitrogen （BUN） and creatiniue （Cr） concentrations.After blood sampling, the animals were sacrificed, and the left kidneys were removed for determination of tumor necrosis factor-alpha （TNF-α） , interleukin-6 （IL-6） and IL-8 and IL-10 contents （by using enzyme-linked immunosorbent assay）, and malondialdehyde （MDA） content （by thiobarbituric acid method）, and superoxide dismutase （SOD） activity （using xanthine oxidase method）.Results Compared with group S, the serum BUN and Cr concentrations, and contents of TNF-α, IL-6, IL-8 and MDA in renal tissues were significantly increased, and the IL-10 content and SOD activity in renal tissues were decreased in the other four groups （P〈0.05）.Compared with group I/R, the serum BUN and Cr concentrations, and contents of TNF-α, IL-6, IL-8 and MDA in renal tissues were significantly decreased, and the IL-10 content and SOD activity in renal tissues were increased in OL, OM and OH groups （P〈0.05）.The serum BUN and Cr concentrations, and contents of TNF-α,IL-6, IL-8 and MDA in renal tissues were gradually decreased, and the IL-10 content and SOD activity in renal tissues were gradually increased with increasing dosage of oxycodone in OL, OM and OH groups （P〈 0.05）.Conclusion Oxycodone 2, 4, and 6 mg/kg can alleviate renal I/R injury in a dose-dependent manner in rats, and the mechanism is related to inhibition of inflammatory responses and oxidative stress response.