氯胺酮对大鼠肾脏缺血再灌注损伤的影响

目的 探讨氯胺酮对大鼠肾脏缺血再灌注损伤的影响.方法 健康雄性Wistar大鼠24只,随机分为4组(n=6):假手术组(S组)、缺血再灌注组(IR组)、氯胺酮2 ms/kg组(K_1组)及氯胺酮10 mg/kg组(K_2组).采用无创动脉夹夹闭左肾动脉45 min,再灌注6 h,制备大鼠肾脏缺血再灌注模型.K_(1,2)组于再灌注前5 min分别经尾静脉注射氯胺酮2、10 mg/kg.于再灌注6 h时取右心耳血样2 ml,测定血清肌酐(Cr)及尿素氮(BUN)的浓度;光镜下观察肾组织病理学结果 ;采用免疫组织化学法测定肾组织Fas或Caspase-3表达水平;采用TUNEL法检测肾小管上皮细胞凋亡情况,并计算凋亡指数(AI).结果 与S组比较,其余3组血清Cr、BUN的浓度升高,肾组织Fas、Caspase-3的表达上调,AI升高(P<0.01);与IR组比较,K_(1,2)组血清Cr、BUN的浓度降低,肾组织Fus、Caspase-3的表达下调,AI降低(P<0.01);与K_1组比较,K_2组血清Cr、BUN浓度降低,肾组织Fas、Caspase-3的表达下调,AI降低(P<0.01).K_2组肾组织病理损伤较K_1组明显减轻.结论 氯胺酮可减轻肾脏缺血再灌注损伤,且呈剂量依赖性,可能与其抑制肾小管上皮细胞凋亡有关.

Effects of ketamine on renal ischemia-reperfusion injury in rats

Objective To investigate the effects of ketamine on the renal ischemia-reperfusion (IR) injury in rats and the underlying mechanism. Methods Twenty-four male Wistur rats weighing 220-250 g were randomly divided into 4 groups (n=6 each): sham operation group (group S), IR group, ketumine 2 mg/kg group (group K_1), ketamine 10 mg/kg group (group K_2). The rats were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. Renal ischemia was induced by clamping the left renal artery for 45 min followed by 6 h of repednsion using an atraumatic clamp. In group K_1 and K_2, ketaminc 2 and 10 mg/kg were injected via the caudal vein 5 min before the repedusion respectively. The rats were killed at 6 h of reperfusion, and blood samples were collected from the right auricle for measurement of serum creatiniue (Cr) and blood urea nitrogen (BUN) concentrations. Pathological changes in renal tissues were observed with light and electron microscopes. The expression of Fas and Caspsse-3 in the renal tubular epithelial cell was determined by immuno-histochemistry. The apeptosis in the renal tubular epithelial cell was detected by TUNEL assay. Apeptotic index (AI) was calculated. Results Compared with group S, the levels of serum Cr and BUN, expression of Fas and Caspase-3 and AI were significantly increased in group IR, K_1 and K_2 (P < 0.01). The levels of serum Cr and BUN, expression of Fas and Caspase-3 and AI were significantly lower in group K_(1,2) than in group IR and in group K2 than in group K_1 (P<0.01). The microscopic examination showed that the renal IR injury was obviously attenuated in group K_2 compared with group K_1. Conclusion Ketamine can attenuate the renal injury induced by IR in a dose-dependent manner in rats. The underlying mechanism may be related to the inhibition of apoptosis in the renal tubular epithelial cell.