模拟失重环境下腹腔感染大鼠肝脏微循环障碍及抗感染疗效  

Effects of simulated microgravity and intravenous moxifloxacin on hepatic microcirculation of rat with abdominal infection

作　　者：邓忠伟[1] 鲍时明[2] 孙宏伟[2] 姜福全[2] 徐冰心[3] 周金莲[4] 王平[2] 张宏文[2] 崔彦[1] 

机构地区：[1]北京大学解放军第306医院教学医院,100101 [2]解放军第306医院普通外科 [3]解放军第306医院特种医学实验研究中心 [4]解放军第306医院病理科

出　　处：《中华肝胆外科杂志》2015年第8期559-564,共6页Chinese Journal of Hepatobiliary Surgery

基　　金：全军医学科研“十二五”重点项目（BWS11J051）

摘　　要：目的研究模拟失重环境下腹腔感染大鼠肝脏微循环变化及抗感染治疗效果。方法健康雄性成年Wistar大鼠60只，随机分为6组（n=10），分别为模拟失重并腹腔假手术组（microgravity＋sham—operation，MSO）、模拟失重并腹腔感染组（microgravity4-abdominal-infection，MAI）、模拟失重并腹腔感染治疗组（microgravity＋abdominal-infection＋moxifloxacin，MAIM）、正常重力腹腔假手术组（normal—gravity＋sham—operation，NGSO）、正常重力腹腔感染组（normal-gravity＋abdominal-infection，NGAI）和正常重力腹腔感染治疗组（normal-gravity＋abdominal-infection＋moxifloxacin，NGAIM）。采用尾悬吊法建立模拟失重动物模型，盲肠结扎穿孔术（CLP）建立腹腔感染模型。根据分组要求，尾悬吊模拟失重48h时，建立腹腔感染动物模型。MAIM组和NGAIM组动物分别于CLP后0h、24h及48h经尾静脉注射盐酸莫西沙星氯化钠注射液（30mg／kg）。CLP后60h取材，硝酸还原酶法测定血清一氧化氮（NO）水平，蛋白印迹和实时PCR分别检测肝组织中内皮素-1（ET-1）及诱导型一氧化氮合酶（iNOS）蛋白及mRNA表达水平，并光镜下观察肝组织病理变化。结果MAI组及NGAI组可见肝窦增宽，局部淤血，伴有点状坏死，汇管区炎性细胞浸润；MAIM组及NGAIM组的病变程度较MAI和NGAI组减轻。MAI组的血清NO值和肝组织中ET-1和iNOS表达水平最高，显著高于MSO组（P〈0．05）。MAIM组的血清NO值、肝组织中ET-1和iNOS表达均较MAI组明显下降（P〈0．05）。正常重力各组的血清NO值、肝组织中ET-1和iNOS表达与模拟失重各组的情况相类似，除血清NO值外，均不同程度低于模拟失重各组的表达水平。实验各组ET-1、iNOS的蛋白和mRNA表达基本同步。结论模拟失重环境下CLP所致腹腔感染可造成肝脏微循环障碍，静脉使用盐酸莫西沙星对控制感染和改善肝脏病理性榻害有确定Objective To investigate the effects of simulated microgravity and intravenous moxi- floxacin on hepatic microcirculation of rat with abdominal infection. Methods Sixty healthy male adult Wistar rats were divided into 6 groups （n = 10 ） by random number table, including microgravity ＋ sham- operation （ MSO ）, microgravity ＋ abdominal-infection （ MAI ）, mierogravity ＋ abdominal-infection ＋ moxi- floxacin （MAIM）, normal-gravity ＋ sham-operation （NGSO）, normal-gravity ＋ abdominal-infection （NGAI） and normal-gravity ＋ abdominal-infection ＋ moxifloxacin （NGAIM）. Tail-suspension was used to simulate the weightlessness animal model, and cecal ligation and puncture （CLP） model was used to mimic the abdominal infection. According to the experimental design, the CLP procedure was performed in the rats under simulated weightlessness for 48 hours. The injections of moxifloxacin hydrochloride were given via tail vein to the animals of group MAIM and group GAIM at 0 hour, 24 hours and 48 hours post-CLP respectively （30 mg/kg）. At 60 hours post-CLP, blood and liver samples were obtained for analysis of serum NO by Nitrate reductase method, ET-1 and iNOS in liver by Western blotting and real-time PCR respectively. The pathological changes of the fiver were observed under light microscope. Results The light microscope revealed that the hepatic sinusoids were enlarged with local congestion, and there were focal necrosis in the li- ver tissue and inflammatory cell infiltration in portal area. The pathological alterations in group MAIM and group NGAIM were alleviated than that of in group MAI and group NGAI. The value of serum NO and expression of ET-1 and iNOS in liver were significantly increased in group MAI than that of in group MSO （ P 〈 0.05 ） , and the value of serum NO and expression of ET-1 and iNOS in liver were down-regulated sig- nificantly in group MAIM compared with group MAI （ P 〈 0.05 ）. The serum NO and hepatic ET-1 and iNOS in groups of normal gravity

关 键 词：模拟失重 腹腔感染 大鼠 肝脏微循环 盐酸莫西沙星 

分 类 号：R512.62[医药卫生—内科学]