AIM: To investigate the effects of propofol on lipopolysaccharide ( LPS ) - induced activation of p38 mitogen - activated protein kinase ( p38 MAPK ) and inducible nitric oxide synthase ( iNOS ) in brain tissues of rats.METHODS: Sprague - Dawley rats of both sexes were randomly divided into 3 groups ( n = 24 each ): control group, LPS group and LPS + propofol group.The models of LPS - induced brain injury were established by injecting LPS ( 1 mg/kg ) via left internal carotid artery in LPS group.Propofol ( 100 mg/kg ) was given intraperitoneally immediately after the LPS was given in LPS + propofol group.The same volume of normal saline was given to the rats in control group.The rats were decapitated 6 h, 24 h, 48 h and 72 h after administration.The brains were immediately isolated to detect the water content, activation of p38 MAPK and the exepression of iNOS protein.Meanwhile, the pathological changes were observed under light microscope.RESULTS: The water content of the brain was higher in IPS group than that in control group.The protein levels of phosphorylated p38 MAPK( p - p38 MAPK ) and iNOS in LPS group increased 6 h after LPS administration, reached the peak at 24 h, and still higher than those in control group at 48 h and 72 h ( P ＜ 0.05 ).The levels of those indexes were all lower in LPS + propofol group at various time points than those in corresponding LPS group ( P ＜ 0.05 ).The pathological changes were slighter than those in LPS group.The water content of the brain was positively correlated with the levels of p - p38 MAPK and iNOS ( r =0.603, r =0.727 ,P ＜0.05 ).CONCLUSION: Propofol attenuates LPS - induced brain injury by inhibiting the activation of p38 MAPK and down - regulating iNOS expression.%目的:观察异丙酚对脂多糖(LPS)致大鼠脑损伤时脑组织p38丝裂原活化蛋白激酶(p38 MAPK)和诱导型一氧化氮合酶(iNOS)活化的影响.方法:SD大鼠,雌雄不限,随机分为3组(n=24):对照组(C组)、LPS组(LPS组)和LPS+异丙酚组(LPS+P组),LPS组经左颈内动脉注射LPS(1 mg/kg)建立LPS性脑损伤模型,LPS+P组在给予LPS后立即通过腹腔注射给予异丙酚(100 mg/kg),C组给予等容量生理盐水.分别于注射异丙酚后6、24 、48和72 h处死6只大鼠,取大脑皮质组织,测定脑组织含水量、磷酸化p38 MAPK和iNOS表达水平,光镜下观察脑组织形态及病理变化.结果:与C组比较,LPS组各时点脑组织含水量升高,脑组织磷酸化p38 MAPK和iNOS表达水平均于6 h开始增加,24 h达高峰,48 h及72 h各指标仍高于C组(P<0.05);与LPS组相比,LPS+P组脑组织含水量、磷酸化p38 MAPK和iNOS的表达水平降低( P<0.05).脑组织含水量与磷酸化p38 MAPK、iNOS水平呈正相关(r=0.603,r=0.727,P<0.05).LPS+P组脑组织病理学损伤轻于LPS组.结论:异丙酚可减轻LPS所致的大鼠脑损伤,其机制可能与异丙酚抑制脑组织p38 MAPK活化,下调iNOS的表达,进而减轻炎性反应有关.
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