头孢曲松钠对大鼠局灶性脑缺血损害保护作用机制研究

Study of tThe mechanism of ceftriaxone on focal cerebral ischemia in rats

目的探讨大鼠局灶性脑缺血模型中头孢曲松钠保护作用机制。方法制备Wistar大鼠局灶性脑缺血模型,随机分为假手术组(S组)、脑缺血组(M组)、头孢曲松钠组(C组),C组为缺血90min时给予头孢曲松钠200mg/kg;在缺血后24h测定谷氨酸转运体-1(GLT-1)mRNA表达、超氧化物歧化酶(SOD)活性、丙二醛(MAD)含量以及钙神经素(calcineurin,CaN)和钙激活中性蛋白酶(calpain)活性。结果 M组、C组较S组GLT-1mRNA表达相对量减少,SOD活性降低,MAD含量增加,CaN和calpain活性升高;C组较M组大鼠GLT-1mRNA表达量明显增加,SOD活性升高,MAD含量减少,CaN和calpain活性降低(P<0.01)。结论头孢曲松钠通过增加GLT-1表达、减轻氧自由基损伤作用以及降低钙超载激活的蛋白水解酶CaN、calpain活性等多种机制保护缺血脑组织,发挥神经保护作用。

Objective To explore the possible mechanism of ceftriaxone on focal cerebral ischemia in rats.Methods Focal cerebral ischemic model was established in Wistar rats.Rats were divided into sham（S）group,ischemic group（M）and ceftriaxone（C）group.Ceftriaxone（200mg/kg）was ip injected 90min after the operation.At 24h after the focal cerebral ischemia,expression of GLT-1mRNA,superoxide dismutase（SOD）,malondiadehyde（MDA）,and calcineurin and calpain enzymes activities were measured.Results Compared with S group,expression of GLT-1mRNA and SOD activity were lower and MDA content and calcineurin and calpain enzymes activities were higher in M and C group.Expression of GLT-1mRNA and SOD activity were higher and MDA content and calcineurin and calpain enzymes activities were lower in C group compared with M group（P0.01）.Conclusion Ceftriaxone has neuroprotective effect against focal cerebral ischemia in rats by up-regulating GLT-1 expression,reduceing oxygen free radical damage and the activities of calcium overload activated protein hydrolysis enzyme calcineurin and calpain.