异丙酚对内毒素所致急性肺损伤大鼠肺组织TGF—β1／Smad2信号通路的影响

Effect of propofol on transforming growth factor-β1/Smad2 signaling pathway in lung tissues in rats with lipopolysaccharide-induced acute lung injury

目的探讨异丙酚对内毒素所致急性肺损伤大鼠肺组织转化生长因子（TGF）-β1／Smad2信号通路的影响。方法健康雄性Wistar大鼠56只，7-8周龄，260～300g，采用随机数字表法，将其随机分为5组：正常对照组（A组，n=8）、LPS组（B组，n=12）、异丙酚不同时点给药组（C组～E组，n=12）。A组给予等容量生理盐水，B组静脉注射脂多糖8mg／kg，C组、D组和E组分别于给予LPS前1h、给予LPS后即刻和给予LPS后1h时静脉注射异丙酚5mg／kg，随后以10mg·kg^-1·h^-1速率输注至给予LPS后5h。分别于给予LPS前即刻、给予LPS后1、3、5h时采集动脉血样，测定pH值和PaO2，随后处死大鼠，取肺组织，计算湿，干重比（W／D），测定肺组织TGF—β1 mRNA和Smad2表达。结果与A组比较，B组和E组pH值和PaO2降低，肺组织W／D升高，TGF—β1 mRNA和Smad2表达上调（P〈0．05）；与B组比较，C组和D组pH值和PaO2升高，肺组织W／D降低，TGF-β1 mRNA和Smad2表达下调，E组PaO2升高（P〈0．05）。结论异丙酚减轻内毒素所致ALI的机制与抑制TGF-β1／Smad2通路激活有关。

Objective To investigate the effect of propofol on transforming growth factor （TGF）-β1/Smad2 signaling pathway in lung tissues in rats with lipopolysaccharide （LPS）-induced acute lung injury （ALI）. Methods Fifty-six male Wistar rats, aged 7-8 weeks, weighing 260-300 g, were randomly divided into 5 groups： control group （group A, n = 8） ; LPS group （group B, n = 12） ; 3 propofol groups （groups C, D, E, n = 12）. ALI was induced by intravenous LPS 8 mg/kg in groups B, C, D and E. In groups C, D, E, propofol 5 mg/kg was injected intravenously before LPS administration and at 0 and 1 h after LPS administration, respectively, followed by infusion of propofol at 10 mg· kg^- 1 ·h^- 1 until 5 h after LPS administration. Group A received the equal volume of normal saline. Arterial blood samples were collected immediately before LPS administration and 1, 3 and 5 h after LPS administration for determination of pH value and PaO2. Then the animals were sacrificed and the lungs were immediately removed for calculation of the wet/dry lung weight ratio and for determination of the expression of TGF-β1- mRNA and Smad2 in lung tissues. Results Compared with group A, pH value and PaO2 were significantly decreased, wet/dry lung weight ratio was increased and the expression of TGF-β1 mRNA and Smad2 was up-regulated in groups B and E （ P 〈 0.05）. Compared with group B, pH value and PaO2 were significantly increased, wet/dry lung weight ratio was decreased and the expression of TGF-β1 mRNA and Smad2 was down-regulated in groups Cand D, and PaO2 was significantly increased in group E （ P 〈 0.05 ）. Conclusion The mechanism by which propofol alleviates ALl induced by LPS is related to inhibition of TGF-~β1/Smad2 signaling pathway.