右美托咪定联合氯胺酮对大鼠肾脏缺血再灌注损伤的保护作用

The protective effect of dexmedetomidine combined with ketamine on renal ischemia reperfusion injury in rats

目的探讨右美托咪定(Dex)联合氯胺酮(Ket)对大鼠肾脏缺血再灌注(IR)损伤的保护作用。方法将40只雄性大鼠随均分为5组:假手术组(Sham组)、缺血再灌注损伤组(IR组)、Dex预处理组(D组)、Ket预处理组(K组)及Dex联合Ket预处理组(DK组),每组8只。5组分别于缺血前20min腹腔注射生理盐水(10 m L/kg)、生理盐水(10 m L/kg)、Dex(10 m L/kg)、Ket(10 m L/kg)以及Dex(5 m L/kg)+Ket(5 m L/kg)。于IR后2 h收集大鼠血清及肾组织标本。检测大鼠血清中尿素氮(BUN)和肌酐(Cr)含量变化,以及肾组织匀浆中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量变化,并观察肾脏组织结构的病理变化。结果 (1)IR组、D组、K组及DK组血清BUN和Cr含量均较Sham组显著升高(P<0.01);但D组、K组及DK组血清BUN和Cr含量均明显低于IR组(P<0.01);DK组血清BUN和Cr含量明显低于D组及K组(P<0.05)。(2)IR组、D组、K组及DK组肾组织中MDA含量均较Sham组显著升高(P<0.01)、SOD活性均较Sham组显著降低(P<0.01);但D组、K组及DK组肾组织中MDA含量均显著低于IR组(P<0.01)、SOD活性均显著高于IR组(P<0.01);DK组肾组织中MDA均显著低于D组及K组(P<0.05)、SOD活性均显著高于D组及K组(P<0.05)。(3)IR组、D组、K组及DK组肾组织损伤均较Sham组显著加重;但D组、K组及DK组肾组织损伤程度均明显低于IR组;DK组肾组织损伤程度明显低于D组和K组。结论 Dex联合Ket对大鼠肾脏缺血再灌注损伤可产生保护作用,其作用机制可能与药物的抗氧化及抗炎作用有关,但具体机制仍有待进一步探索。

Objective To investigate the protective effects of dexmedetomidine（Dex） combined with ketamine（Ket） on renal ischemia reperfusion injury in rats.Methods A total of 40 male rats were randomly divided into 5 groups, 8 rats in each group： Sham operation group （Sham group）, renal ischemia reperfusion injury group （IR group）, Dex group （D group）, Ket group （K group）, and Dex combined with Ket group （DK group）. Five groups were respectively injected with normal saline （10 mL/kg）, normal saline （10 mL/kg）, Dex （10 mL/kg）, Ket（10 mL/kg）, and Dex（5 mL/kg） combined with Ket（5 mL/kg） by intraperitoneal injection 20 min before ischemia. The serum and renal tissue samples were collected two hours after renal reperfusion. The contents of BUN and Cr in serum were detected. The activities of SOD and the contents of MDA in renal tissue homogenate were tested. The pathological changes of renal tissue structure were observed under light microscope.Results ①The contents of BUN and Cr in group IR,D,K and DK were significantly higher than those in Sham group（ P 〈0.01）. The contents of BUN and Cr in group D,K and DK were higher than those in IR group （ P 〈0.01）. The contents of BUN and Cr in DK group were significantly lower than those in group D and K （ P 〈0.05）.②Compared with Sham group, the contents of MDA were significantly increased, the activities of SOD were significantly decreased in group IR,D,K,DK（ P 〈0.01）. In group D,L and DK, the contents of MDA were significantly lower, and the activities of SOD were significantly higher than that in IR group （ P 〈0.01）. The contents of MDA were significantly lower, the activities of SOD were significantly higher in DK group than those in group D and K （ P 〈0.05）. ③The severity of renal tissue damage in group IR, D, K and DK was significantly higher than that in Sham group. The degree of renal tissue damage in group D, K and DK was significantly lower than that in IR group. The damage degree of renal tissue in DK group was significantly lower than that in group D and K.Conclusion Dexmedetomidine combined with Ketamine has the protective effect on renal ischemia reperfusion injury. The mechanism may be related to the anti-oxidation and anti-inflammatory effects of drugs, but the specific mechanism needs to be further explored.