盐酸戊乙奎醚对内毒素血症新生大鼠肠损伤的影响

Effect of penehyclidine hydrochloride on endotoxemia-induced intestinal injury in neonatal rats

目的 探讨盐酸戊乙奎醚对内毒素血症新生大鼠肠损伤的影响.方法 健康SD大鼠90只,7日龄,体重16～20 g,采用随机数字表法,将其分为3组（n=30）：对照组（C组）、内毒素血症组（LPS组）和盐酸戊乙奎醚组（P组）.腹腔注射脂多糖（LPS）5 mg/kg制备内毒素血症致肠损伤模型.P组于注射LPS前、后30 min时分别腹腔注射盐酸戊乙奎醚2 mg/kg,C组腹腔注射等容量生理盐水.腹腔注射LPS或生理盐水后2、6和12 h（T1-3）时随机取10只大鼠处死,取回肠组织测量湿重/干重（W/D）比值,光镜下观察回肠组织病理学结果,采用ELISA法检测肠组织TNF-α、IL-6、缺氧诱导因子-1α（HIF-1α）和谷氨酰胺（Gln）含量.结果 与C组比较,LPS组和P组肠组织W/D比值、TNF-α、IL-6和HIF-1α含量升高,Gln含量降低（P＜0.05）;与LPS组比较,P组肠组织W/D比值、TNF-α、IL-6和HIF-1α含量降低,Gln含量升高（P＜0.05）.P组肠组织病理学损伤程度较LPS组减轻.结论 盐酸戊乙奎醚可减轻内毒素血症新生大鼠肠损伤,其机制可能与其下调HIF-1α表达,上调Gin表达,减轻炎性反应有关.

Objective To investigate the effect of penehyclidine hydrochloride on endotoxemiainduced intestinal injury in neonatal rats.Methods Ninety healthy neonatal Sprague-Dawley rats,aged 7days,weighing 16-20 g,were randomly divided into 3 groups （n =30 each） using a random number table：control group （group C）,lipopolysaccharide （LPS） group,and penehyclidine hydrochloride group （group P）.Endotoxemia was induced by intraperitoneal LPS 5 mg/kg in LPS and P groups.In group P,penehyclidine 2 mg/kg was injected intraperitoneally at 30 min before and after LPS injection.The equal volume of normal saline was given in group C.At 2,6 and 12 h after LPS or normal saline administration,10 rats in each group were randomly chosen and sacrificed.The ileum was removed to detect wet/dry lung weight ratio （W/D ratio） and contents of tumor necrosis factor-α （TNF-α）,interleukin-6 （IL-6）,hypoxia-inducible factor 1 alpha （HIF-1α） and glutamine （Gln）,and for examination of the pathologic changes of the ileum with light microscope.Results Compared with group C,the W/D ratio and contents of TNF-α,IL-6 and HIF-1α were significantly increased,and the content of Gln was decreased at each time point in LPS and P groups.Compared with group LPS,the W/D ratio and contents of TNF-α,IL-6 and HIF-1α were significantly decreased,the content of Gin was increased at each time point,and the pathologic changes of the ileum were mitigated in group P.Conclusion Penehyclidine hydrochloride can reduce endotoxemia-induced intestinal injury in the neonatal rats,and down-regulated expression of HIF-1α,up-regulated expression of Gln and attenuated inflammatory responses may be involved in the mechanism.