盐酸戊乙奎醚预先给药对大鼠内毒素性急性肺损伤时缺氧诱导因子-1α表达的影响

Effect of penehyclidine hydrochloride pretreatment on hypoxia-inducible factor-lalpha expression in lung tissues in rats with acute lung injury induced by lipopolysaccharide

目的评价盐酸戊乙奎醚预先给药对大鼠内毒素性急性肺损伤时缺氧诱导因子-1α（HIF-1α）表达的影响。方法健康成年雌性SD大鼠120只，体重180～220g，采用随机数字表法，将大鼠随机分为3组（n=40）：对照组（C组）、急性肺损伤组（ALI组）和盐酸戊乙奎醚预先给药组（P组）。采用腹腔注射内毒素5mg／kg制备大鼠内毒素性急性肺损伤模型。C组腹腔注射等量生理盐水，P组于注射内毒素前30min时腹腔注射盐酸戊乙奎醚2mg／kg。于注射内毒素后2、4、8和24h时各组随机取8只大鼠处死取肺，采用RT-PCR法检测肺组织HIF-1αmRNA的表达。于注射内毒素后6h时随机取8只大鼠处死取肺，测定湿干重比（W／D比）.用ELISA法检测肺组织IL-6的含量，光镜下观察肺组织病理学结果。结果与C组比较，ALI组和P组注射内毒素后6h时W／D比、IL-6含量、各时点HIF-1α表达水平升高（P〈0．05）；与ALI组比较，P组注射内毒素后6h时W／D比、IL-6含量、各时点HIF-1α表达水平降低（P〈0．05）。P组肺组织病理学损伤程度较ALI组减轻。结论盐酸戊乙奎醚预先给药通过下调肺组织HIF-1α表达，抑制炎性反应，从而减轻大鼠内毒素性急性肺损伤。

Objective To investigate the effects of penehyclidine hydrochloride （PHCD） pretreatment on hypoxia-inducible factor-1αlpha （HIF-lct） expression in lung tissues in rats with acute lung injury （ALl） induced by lipopolysaccharide （LPS）.Methods One hundred and twenty female Sprague-Dawley rats, weighing 180-220 g, were randomly divided into 3 groups （ n = 40 each） ： control group （group C）, ALl group and PHCD pretreatment group （group P）. ALl was induced by intraperitoneal LPS 5 mg/kg in ALl and P groups. The equal volume of normal saline was given intraperitoneally in group C. Group P received intraperitoneal PHCD 2 mg/kg at 30 min before LPS administration. Eight rats in each group were chosen at 2, 4, 8 and 24 h after LPS administration, and the lung was removed for determination of HIF-1α mRNA expression in lung tissues by RT-PCR. Eight rats in each group were chosen at 6 h after LPS administration, and the lung was removed for determination of W/D lung weight ratio and IL-6 content （by ELISA） and for microscopic examination. Results The W/D lung weight ratio and IL- 6 content at 6 h after LPS administration and HIF-1α mRNA expression at each time point after LPS administration were significantly higher in groups P and ALI than in group C （ P 〈 0.05）, and lower in group P than in group ALl （ P 〈 0.05）. The pathological damage was significantly ameliorated in group P as compared with group ALI. Conclusion PHCD can reduce LPS-induced ALI through down-regu1αtion of HIF-1α expression in lung tissues and inhibition of the inf1αmmatory response in rats.