Zhou Rong, Hu De-Yao, Liu Liang-Ming, Zhou Xue-Wu
The Second Department of Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
Acta Pharmacol Sin. 2002 Nov;23(11):1023-8.
To evaluate the protective effects of apocynin on "two-hit" injury in rats.
"Two-hit" injury model of rat was induced by hemorrhagic shock (40 mmHg for 45 min) followed by iv administration of lipopolysaccharide (LPS, 150 microg/kg). Rats were randomized into seven groups: Sham, LPS, hemorrhage, hemorrhage/LPS, and hemorrhage/LPS+apocynin (2.5, 5.0, and 10.0 mg/kg). Apocynin was dissolved in the resuscitation fluid (normal saline, NS) and administered iv for 2 h. After LPS or NS administration, the survival rates at 8 h, 16 h, 24 h, and 48 h were monitored. The content of malondialdehyde (MDA) was measured in lung at 3 h and 6 h after iv LPS and in serum before hemorrhage, after hemorrhage, and at 0, 0.5, 1, 2, 4, and 6 h after iv LPS. Myeloperoxidase (MPO) activity in lung and liver was examined at 3 h and 6 h after iv LPS/NS.
After "two-hit" injury, the survival rates of rats at 8 h, 16 h, 24 h, and 48 h were 64.3 %, 35.7 %, 28.6 %, and 14.3 % respectively, there were significant differences as compared to sham group (P<0.05 or P<0.01, respectively), the MDA level in lung and serum were significantly enhanced (P<0.01) as compared to sham group, and MPO activity in lung and liver after "two-hit" injury was also significantly increased (P<0.01). Apocynin treatment enhanced the mean arterial pressure (MAP) of hemorrhagic shock rats dose-dependently (P<0.05), increased the survival rate of "two-hit" injury rats, decreased the serum and lung MDA content, and downregulated MPO activity in lung and liver.
Apocynin could preventively ameliorate "two-hit" injury in rats induced by hemorrhagic shock and LPS insult.
评估阿朴吗啡对大鼠“两次打击”损伤的保护作用。
通过失血性休克（40 mmHg，持续45分钟），随后静脉注射脂多糖（LPS，150微克/千克）诱导大鼠“两次打击”损伤模型。将大鼠随机分为七组：假手术组、LPS组、失血性休克组、失血性休克/LPS组以及失血性休克/LPS + 阿朴吗啡（2.5、5.0和10.0毫克/千克）组。阿朴吗啡溶解于复苏液（生理盐水，NS）中，静脉注射2小时。给予LPS或NS后，监测8小时、16小时、24小时和48小时的存活率。在静脉注射LPS后3小时和6小时以及出血前、出血后以及静脉注射LPS后0、0.5、1、2、4和6小时测定血清中的丙二醛（MDA）含量。在静脉注射LPS/NS后3小时和6小时检测肺和肝脏中的髓过氧化物酶（MPO）活性。
“两次打击”损伤后，大鼠在8小时、16小时、24小时和48小时的存活率分别为64.3%、35.7%、28.6%和14.3%，与假手术组相比有显著差异（分别为P<0.05或P<0.01），肺和血清中的MDA水平与假手术组相比显著升高（P<0.01），“两次打击”损伤后肺和肝脏中的MPO活性也显著增加（P<0.01）。阿朴吗啡治疗剂量依赖性地提高失血性休克大鼠的平均动脉压（MAP）（P<0.05），提高“两次打击”损伤大鼠的存活率，降低血清和肺中的MDA含量，并下调肺和肝脏中的MPO活性。
阿朴吗啡可预防性改善失血性休克和LPS损伤诱导的大鼠“两次打击”损伤。
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