摘要
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iN-OS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。
AIM: To investigate the effects of propofol on lipopolysaccharide (LPS) -induced activation of p38 mitogenactivated 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 LPS 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.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2011年第8期1639-1642,共4页
Chinese Journal of Pathophysiology