摘要
目的探讨乌司他丁对SD大鼠脓毒症脑损伤的保护作用及其机制。方法将SD大鼠随机分为4组:假手术组(Sham)、模型组(cLP)、乌司他丁低剂量组(5x10^4U/kg)和乌司他丁高剂量组(10x10^4U/kg)。采用盲肠结扎穿孔(CLP)法复制脓毒症模型。术后治疗组动物给予乌司他丁5xl04U/kg或10x10^4/kg腹腔注射,1次/日。造模72h后取脑,观察脑组织病理改变及细胞凋亡,并测定各组脑组织一氧化氮(No)、诱导型一氧化氮合酶(iNOS)、一氧化氮合酶(Nos)、活性氧簇(ROS)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性变化。结果与Sham组比较,CLP组正常神经元减少,凋亡细胞增加,NO、iNOS、NOS、ROS和MDA含量增加,SOD活性下降(P〈0.01);与CLP组比较,乌司他丁高、低剂量组以上指标均有所改善(P〈0.05或0.01),且高剂量组较低剂量组改善更明显(P〈0.05)。结论乌司他丁对脓毒症诱发的脑损伤有保护作用,其机制可能与抑制氧/氮自由基生成、抗凋亡有关。
Objective To explore the mechanism of protective effects of ulinastatin on sepsis-induced brain injury in rats. Methods 48 male SD rats were randomly divided into 4 groups (n =12), Sham group, CLP group, low-dose ulinastatin group (UTI 1), and high-dose ulinastatin group (UTI 2). Cecal ligation and puncture (CLP) were used to reproduce septic shock model. Ulinastatin groups of 5x 10^4 U/kg or 10x10^4 U/kg ulinastatin were given via intraperitoneal injection once a day for 3 days after operation, respectively. In sham group, operation was performed without CLP. HE staining and TUNEL method were used to investigate pathologic change and apoptosis at 72-hour after the operation. The NO, iNOS, NOS, MDA contents and the activity of SOD in brain were also investigated. Results Comparing with sham group, it reflected a decreased normal neurons, increased neural rate of cell apoptosis, and higher content of NO, iNOS, NOS, ROS and MDA, with a lower SOD activity in CLP group (P 〈0.01). Comparing with CLP group, both ulinastatin groups demonstrated an improved parameters (P 〈0.05 or 0.01). As a matter of fact, the high-dose ulinastatin group reflected an even better improvement than the low-dose ulinastatin group (P 〈0.05). Conclusion Ulinastatin is considered to provide protection against sepsis-mediated brain injure by decreasing oxygen/nitrogen free radicals and neural cell apoptosis.
出处
《中国急救复苏与灾害医学杂志》
2013年第6期530-532,568,共4页
China Journal of Emergency Resuscitation and Disaster Medicine
关键词
乌司他丁
脓毒症
凋亡
自由基
Ulinastatin
Sepsis
Apoptosis
Free radical
作者简介
通讯作者:廖晓星,Email:liawens@163.com