目的探讨右美托咪啶对急性肾缺血再灌注损伤(ischemia reperfusion injury, IRI)的保护作用及其机制。方法 SD大鼠40只, 随机分为:对照(S) 组、缺血-再灌注 (IR) 组、右美托咪啶(Dex)组、右美托咪啶+育亨宾(Dex+Yoh)组和育亨宾(Yoh)组五组, 每组8只。S组:仅结扎右侧肾蒂, 左肾蒂游离。IR组:结扎右侧肾蒂, 夹闭左侧肾蒂1 h后, 开放灌注4 h。Dex组:通过尾静脉以5 μg/(kg·h) 的速度持续泵注右美托咪啶1 h, 余同IR组。Dex+Yoh组:输注右美托咪啶前10 min, 静脉注射育亨宾1 mg/kg, 其余同Dex组。Yoh组:静注育亨宾1 mg/kg, 其余同IR组。分别检测血清尿素氮(BUN)、肌酐(Cr), 肾组织超氧化物歧化酶(SOD)、丙二醛(MDA), 光镜观察肾组织的病理学变化。结果 与S组比较, IR组血BUN、Cr含量, 肾组织MDA水平显著增加, SOD水平下降(P<0.05);与IR组比较, Dex组血BUN和Cr含量下降(P<0.05), 肾组织SOD水平升高, MDA 水平下降(P<0.05), Dex+Yoh组和Yoh组均无显著变化(P>0.05), 后两组之间比较亦无显著差异(P>0.05);与S组比较, IR组、Dex+Yoh和Yoh组肾组织病理分级升高(P<0.05);与IR组比较, Dex组分级下降(P<0.05), Dex+Yoh和Yoh组无显著差异(P<0.05)。结论 右美托咪啶能减轻肾缺血再灌注的损伤程度, 其机制可能与激活α₂肾上腺素受体介导的抑制氧自由基堆积、增强机体的抗氧化能力等有关。

Objective To determine the effects of dexmedetomidine on renal ischemia reperfusion injury (IRI)in rats and to study the underlying mechanisms. Methods Forty SD rats were allocated randomly into 5 groups (n=8 per group). Sham group (S): rats received continuous intravenous infusion of normal saline and clamping the right renal pedicles.IR group (IR): the rats received continuous intravenous infusion of normal saline, and renal IRI was induced by clamping the both renal pedicles 1 h followed by declamping (reperfusion) for 4h. Dex group: intravenous dexmedetomidine was infused continuously at 5 μg/(kg·h)for 1h before the renal ischemia. Dex+Yoh group: yohimbine hydrochloride (1 mg/kg) was administered intravenously 10 min before dexmedetomidine. Yoh group: only yohimbine hydrochloride (1 mg/kg) was administered intravenously 10 min before the renal ischemia. Serum blood urea nitrogen (BUN), creatinine (Cr), kidney superoxide dismutase (SOD) and malonaldehyde (MDA) were detected. Renal histopathology lesions were examined. Results Compared with group S, the serum BUN and Cr, renal MDA inreased while SOD decreased significantly in group IR (P<0.05). Compared with group IR, the serum BUN and Cr, renal MDA decreased while SOD increased significantly in group Dex (P<0.05). The serum BUN and Cr, renal MDA and SOD did not differred in group Dex+Yoh and Yoh (P>0.05). Compared with group S, the pathological scale in group IR, Dex+Yoh and Yoh were higher (P<0.05). The pathological scale in group Dex was lower than that in group IR (P<0.05). Conclusions Dexmedetomidine attenuates renal IRI, partly through the inhibition of oxygen derived free radicals via the activation of the α₂-adrenoceptor.