曲马多对大鼠脑缺血再灌注损伤的保护作用

Protective effect of tramadol on rat with cerebral ischemia-reperfusion injury

目的研究曲马多(Tramadol,TRA)对大鼠脑缺血再灌注损伤的影响。方法构建Wistar大鼠的大脑中动脉栓塞再灌注模型(Middle cerebral artery occlusion/reperfusion,MCAO/R),将大鼠随机分为假手术组,模型组和实验组。实验组大鼠尾静脉注射20 mg·kg^(-1)曲马多,假手术组和模型组大鼠尾静脉注射0.4 mL·kg^(-1)生理盐水。用Longa评分法评估大鼠的神经功能缺损情况;用试剂盒检测大鼠脑组织中超氧化物歧化酶(SOD),乳酸脱氢酶(LDH)及丙二醛(MDA)含量,用酶联免疫吸附(ELISA)法检测大鼠脑组织中肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β)含量;用蛋白质印迹法检测大鼠脑组织中Toll样受体4(Toll-like receptor 4,TLR4)表达。结果假手术组、模型组和实验组的Longa评分分别为0,3.40±0.49和2.20±0.41;TNF-α含量分别为(117.19±15.37),(210.05±35.33)和(159.74±20.54)pg·mL^(-1);IL-1β含量分别为(73.91±10.48),(135.76±21.08)和(102.69±11.03)pg·mL^(-1);SOD含量分别为(105.41±12.33),(75.41±7.07)和(93.77±10.51)U·mg^(-1);LDH含量分别为(29.06±3.01),(41.55±4.01)和(30.12±2.99)U·mg^(-1);MDA含量分别为(6.41±0.81),(12.03±1.73)和(9.33±1.12)μmol·mg^(-1)。以上指标,模型组与假手术组相比,实验组与模型组相比,差异均有统计学意义(均P<0.05)。结论曲马多可通过抗炎及抗氧化应激作用改善MCAO/R大鼠的神经功能损伤,与TLR4表达下调有关。

Objective To explore the effect of tramadol(TRA)on rats with cerebral ischemia-reperfusion injury.Methods Wistar rats with middle cerebral artery occlusion/reperfusion(MCAO/R)were established,and rats were randomly divided into sham operation group,model group and experimental group.Rats in experimental group were injected with TRA 20 mg·kg^(-1) through the tail vein,rats in sham operation group and model group were injected with 0.4 mL·kg^(-1) normal saline through the tail vein.The Longa scoring method was used to evaluate the neurological deficit of rats.The kits were used to detect the content of superoxide dismutase(SOD),lactate dehydrogenase(LDH)and malondialdehyde(MDA)in brain tissue of rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect the content of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in brain tissue of rats.The expression of toll-like receptor 4(TLR4)in brain tissue of rats was detected by Western blot assay.Results The Longa scores of sham operation group,model group and experimental group were 0,3.40±0.49 and 2.20±0.41;the levels of TNF-αwere(117.19±15.37),(210.05±35.33)and(159.74±20.54)pg·mL^(-1);the levels of IL-1βwere(73.91±10.48),(135.76±21.08)and(102.69±11.03)pg·mL^(-1);the levels of SOD were(105.41±12.33),(75.41±7.07)and(93.77±10.51)U·mg-1;the levels of LDH were(29.06±3.01),(41.55±4.01)and(30.12±2.99)U·mg-1;the levels of MDA were(6.41±0.81),(12.03±1.73)and(9.33±1.12)μmol·mg-1.The difference was statistically significant between sham operation group and model group,as well as model group and experimental group(all P<0.05).Conclusion Tramadol can improve the neurological damage of MCAO/R rats through inhibiting inflammation and oxidative stress,which was related with the under-expression of TLR4.