右美托咪定联合浅低温处理对大鼠脑缺血术后认知功能的影响

Effects of Dexmedetomidinein Combination with Mild Hypothermy on Cerebral Ischema-reperfusion Injury in Rats

目的通过比较右美托咪定联合浅低温治疗大鼠脑缺血损伤与单一治疗对中枢神经保护的效果并探讨其可能机制。方法将64只雄性SD大鼠随机分成4组:缺血再灌注组(I),浅低温组(T),右美托咪定组(D),浅低温联合右美托咪定组(DH)。建立大鼠脑缺血损伤模型,全脑缺血前,I组与D组维持大鼠颞肌温度37.5℃,T组与DH组维持大鼠颞肌温度35℃约30min,温度稳定后D组和DH组腹腔注射右美托咪定100μg/kg预处理,于再灌注12h(T1)、24h(T2)和72h(T3)时行神经功能缺陷评分(NDS评分),然后各组随机处死8只大鼠,取脑组织采用干湿重法测量缺血脑组织含水量,每组另取6只大鼠,采用ELISA法测定肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的含量。结果与I组比较,T组,D组,DH组3个时点的NDS评分降低(均P<0.05);右美托咪定联合浅低温可以改善大鼠脑缺血后神经功能障碍,缩小梗死体积(均P<0.01);DH组的髓过氧化物酶(MPO)、IL-6、TNF-α含量降低(均P<0.01)。结论右美托咪定联合浅低温对大鼠脑缺血损伤时神经保护作用优于单一治疗的效果,其机制可能与抑制炎症反应有关。

Objective To examine the effect of dexmedetomidine combined with mild hypothermy on cerebral ischema- reperfusion injury in rats and the possible mechanism. Methods The SD male rat models of cerebral ischema reperfusion injury were established. Sixty-four model rats were randomly divided in 4 groups：ischema reperfusion groups（group I） ,mild hypother- my group（group T）, dexmedetomidine group（group D）, dexmedetomidine and mild hypothermy combined group（group I）H）. The temporalis of the rats in both groups I and D was kept at a temperature of 37.5℃ for 30 rain and that of the rats in both groups T and DH at 35℃ for the same period of time before cerebral ischemia-reperfusion. Thereafter,dexmedetomidine（ 100 μg/kg）was intraperitoneally injected into the animals in groups D and DH and saline（1 mL/kg）into rats in the groups I and T. The neurological deficit score（NDS）was obtained 12（T1）,24（T2）and 72（T3）h after ischemia reperfusion. Eight rats in each group were randomly selected and sacrificed. The brain tissues were harvested for determination of brain water content by means of dry-wet weight method. ELISA was used to detect the expression of TNF-a and IL- 6 in blood of other six rats in each group. Results The NDS was significantly reduced in groups T, D and DH when compared with group I （P 〈 0.05） Dexmedetomidine in combination with mild hypothermy could ameliorate neurological dysfunction and decrease infarct volume caused by cerebral ischemia reperfusion（P〈0.01）. The contents of MPO,IL-6 and TNF-a were significantly reduced in the group DH（P〈0.01）. Conclusion Dexmedetomidine in combination with mild hypothermy could better protect against brain ischema-reperfusion injury than a single therapy and the possible mechanism may involve the inhibition of the inflammatory re- action.