丙泊酚对大鼠肾缺血-再灌注期血清白细胞介素-8的影响

Effect of propofol on interleukin-8 following renal ischemia-reperfusion injury in rats

目的观察丙泊酚对大鼠肾缺血-再灌注期血清白细胞介素-8(IL-8)的合成和释放的影响,并探讨其肾保护机制。方法选用12~14周雄性大鼠75只,随机分为三组,每组25只,以无创动脉夹夹闭双侧肾蒂60min制备急性肾缺血-再灌注模型。A组为肾缺血-再灌注组,B组为丙泊酚处理组,C组为假手术组。各组设立五个时间观察点:缺血前10min(T0),缺血60min(T1),再灌注1h(T2)、3h(T3)、6h(T4),每个时间点5只大鼠。C组:肾脏缺血60min,缺血前5min从股静脉注射丙泊酚20mg/kg,继之经微量泵持续输入丙泊酚(0·5mg/ml)50mg·kg-1·h-1,持续60min;A、B组以等容生理盐水取代丙泊酚,但A组不夹闭双侧肾蒂,术中保持大鼠呼吸、循环稳定。各组大鼠存活至预定时间后再次麻醉取标本,测定血浆丙二醛(MDA)、超氧化物歧化酶(SOD)、血清IL-8,同时用光学显微镜观察肾组织形态学改变及肾小管损伤情况。结果血浆MDA在C组T1~T4时无明显变化,同A组相似,较B组相应时点显著降低,而B组T1~T4时较T0时及A组各时点显著升高;SOD则呈相反变化;C组T1~T3时血清IL-8无明显变化,仅在T4时较T0时和A组有显著升高,而B组在T1~T4时分别增加1·73、2·50、2·76、2·89倍,同C组和A组相比有显著性差异;光镜下观察发现B组肾小管上皮细胞变性、坏死,细胞脱落,肾小管管腔变窄,肾间质水肿、充血伴炎性细胞浸润明显;而C组以肾小管肿涨为主,个别呈坏死样改变,肾间质水肿、充血、炎性细胞浸润不明显。结论丙泊酚除了有抗氧作用外,还能有效地抑制血清IL-8合成和释放,这可能是丙泊酚减轻肾缺血-再灌注损伤的机制之一。

Objective To determine the inhibitory effect of propofol on the production and release of interleukin-8(IL-8)following renal ischemia-reperfusion injury and evaluate its renal protective mechanism.Methods A model of acute renal ischemia-reperfusion injury was made by clamping renal pedical for 60min.Seventy-five rats were randomly allocated into three groups with 25 rats each,ischemia-reperfusion group (A),propofol group(B) and sham operation group(C).The measurements were performed at five time points:10min before ischemia(T_0),ischemia for 60min (T_1),1h after reperfusin (T_2),3h after reperfusion (T_3),6h after reperfusion (T_4).In group B,propofol 20mg/kg was given intravenously 5min before ischemia and infused at a rate of 50mg·kg^-1·h^-1 for 60min .Other groups of rats received normal saline as contral,but the renal pedical was not occlused in group C. MDA,SOD and IL-8 were observed before,during ischemia and after reperfusion. The renal specimens were exaimined using light microscopy.Results MDA levels in group B and C were significantly lower at T_1-T_4 than those in group A respectively.The changes of SOD were contrary to those of MDA in group B and A. Compared with those at T_0 following ischemia-reperfusion in group C, IL-8 levels remained unchanged at T_1-T_3,increased markedly at T_4 in group B. IL-8 levels in group A were higher markedly during ischemia and reperfusion than those in group C and A.Under light microscope, the injurys of renal cells and renal tubular were more obvious in group A than those in group B. Conclusion In addition to antioxidation,propofol suppresses effectively the production and release of IL-8,and may protect the renal from ischemia and reperfusion injury.