右美托咪定对大鼠不同时间脑缺血再灌注损伤保护作用

Protective Effect of Right Metomidine on Cerebral Ischemia Reperfusion Injury in Rats at Different Times

为了研究右美托咪定对大鼠不同时间脑缺血再灌注损伤的影响,探讨对大鼠脑缺血再灌注损伤保护作用的最佳时间,本研究将7~8周的SPF级雄性SD大鼠80只(体质量(120±10) g)随机分为8组(每组10只):假手术组(Sham组)、缺血再灌注损伤(Zea-Longa法MCAO模型)对照组(IR组)、缺血再灌注损伤+生理盐水组(IR+NS组),其余5组为不同时间缺血再灌注损伤+右美托咪定(不同时间IR+Dex组),这5组分别于缺血后10 min、30min、1 h、2h、3 h恢复脑部血流,同时输注浓度为1.0μg/kg的右美托咪定,输注时间均为1 h。于缺血再灌注后分别用平衡木法测定各组大鼠的的运动功能。ELISA检测各组大鼠脑组织中的NF-κB、TNF-α以及炎症因子IL-1β。RT-qPCR检测糖基化终末产物受体(RAGE)和Toll样受体4 (TLR4) mRNA的水平。Sham组大鼠运动功能没有受影响,IR组与IR+NS组大鼠运动功能明显低于IR+Dex组,有极显著性差异(p<0.01),但是IR+Dex各组的大鼠运动功能也各有差异:10 min IR+Dex组和30 min IR+Dex组与Sham组并没有统计学差异。1h、2h和3 h IR+Dex组大鼠的运动功能与严重下降。IR组与IR+NS组RAGE和TLR4mRNA表达均显著高于Sham组和IR+Dex各组(p<0.05),而IR+Dex各组中,缺血再灌注损伤时间越长,表达越高(p<0.05)。IR组、IR+NS组和IR+Dex各组大鼠血清NF-κB、TNF-α和IL-1β水平均显著高于Sham组,但IR+Dex各组NF-κB、TNF-α和IL-1β的水平显著低于IR组、IR+NS组(p<0.05)。本研究表明,右美托咪定对大鼠脑缺血再灌注损伤具有保护作用,但受时间限制,脑缺血再灌注损伤的时间越长,其保护作用越弱。

To study the effects of dexmedetomidine on cerebral ischemia-reperfusion injury in rats at different time points,and to explore the optimal time for the protection of cerebral ischemia-reperfusion injury in rats,eighty-eight SPF male Sprague-Dawley rats(body weight(120±10) g) were randomly divided into 8 groups(10 in each group):Sham operation group(Sham group);ischemia-reperfusion injury(Zea) Longa MCAO model) control group(IR group);ischemia-reperfusion injury+saline group(IR+NS group);the other five groups were different time ischemia-reperfusion injury+dexmedetomidine(IR+at different times) Dex group:The blood flow in the brain was restored at 10 min,30 min,1 h,2 h,and 3 h after ischemia,and dexmedetomidine was infused at a concentration of 1.0 μg/kg for 1 h.The motor function of each group was determined by the balance beam method after ischemia-reperfusion.ELISA was used to detect NF-κB,TNF-α and inflammatory factor IL-1β in brain tissue of each group.The levels of glycation end product receptor(RAGE) and Toll-like receptor 4(TLR4) mRNA were detected by RT-qPCR.The motor function of Sham group was not affected.The motor function of IR group and IR+NS group was significantly lower than that of IR+Dex group(p <0.01),but the rats of IR+Dex group were significantly different(p<0.01).There were also differences in motor function:there was no statistical difference between the 10 min IR+Dex group and the 30 min IR+Dex group and the Sham group.The motor function of the rats in the 1 h,2 h and 3 h IR+Dex groups was severely decreased.The expressions of RAGE and TLR4 mRNA in IR group and IR+NS group were significantly higher than those in Sham group and IR+Dex group(p<0.05).In IR+Dex group,the longer the ischemia-reperfusion injury time,the higher the expression(p<0.05).The levels of serum NF-κB,TNF-α and IL-1β in the IR group,IR+NS group and IR+Dex group were significantly higher than those in the Sham group,but IR+Dex groups were NF-κB,TNF-α and IL.The level of-1β was significantly lower than that of the IR group and the IR+NS group(p<0.05).It was indicted that Dexmedetomidine had protective effects on cerebral ischemia-reperfusion injury in rats,but it was limited by time,and the longer the cerebral ischemia-reperfusion injury,the weaker its protective effect.