N-乙酰半胱氨酸对体外循环犬肺组织转化生长因子-β1表达的影响

Effects of N-acetylcystine on expression of transforming growth factor beta in the lung during cardiopulmonary bypass in dogs

目的探讨N-乙酰半胱氨酸（NAC）对体外循环（CPB）犬肺组织转化生长因子-β1（TGF-β1）表达的影响。方法成年犬24只，雌雄不拘，体重15～16k，随机分为3组（n=8）：N1组于CPB开始前、N2组于CPB开始后复温前静脉注射NAC 150mg／kg，持续静脉输注NAC 50mg／kg；对照组（C组）给予等容量生理盐水。分别于CPB前（Tn）、CPB开始30min（T1）、停机后15、30、60min（L2-4）时取肺组织，检测TGF-β1表达，测定丙二醛（MDA）含量，光镜下观察病理学结构，于T0、L3及T4时抽取股动脉血行血气分析，计算呼吸指数（RI）。结果与T0时比较，各组于L3,4时RI、余时点肺组织MDA含量升高、TGF-β1表达上调（P〈0．05）；与C组比较，N1组和N2组L3,4时RI、各时点肺组织MDA含量降低，N1组各时点、N2组L2-4时TGF-β1表达下调（P〈0．05）；与N1组比较，N2组L3,4时RI升高、各时点肺组织TGF-β1表达上调（P〈0．05）。N1组和N2组肺部炎性改变较C组明显减轻。结论NAC通过下调肺组织TGF-β1表达，降低炎性反应，可减轻CPB诱发犬肺损伤的程度，且CPB前给药效果更好。

Objective To investigate the effects of N-acetylcystine （NAC） on the expression of transforming growth factor beta-1 （TGF-β1） during cardiopulmonary bypass （CPB） in dogs.Methods Twenty-four healthy adult mongrel dogs of both sexes weighing 15-16 kg were randomly divided into 3 groups （ n = 8 each） ： group Ⅰ received NAC 150 mg/kg iv before CPB （ N1 ） ; group Ⅱ received NAC 150 mg/kg after CPB was started before rewarming （N2） and group Ⅲ received equal volume of normal saline （C）. Lung specimens were obtained before CPB （To ）, at 30 min after CPB was started （T1） and at 15 （T2）, 30 （T3 ） and 60 min （T4） after the termination of CPB for determination of TGF-β1 expression and malondialdehyde （MDA） content in the lung tissue and microscopic examination. Blood samples were collected from femoral artery at T0 , T3 and T4 for blood gas analysis. Respiratory index （RI） was calculated. Results RI and MDA content were significantly increased while TGF-β1 expression was significantly up-regnlated during and after CPB as compared with the baseline values at To in all 3 groups. RI and MDA content were significantly lower while TGF-β1 expression was significantly lower during and after CPB in group N1 and N2 than in group C. RI at T3.4 was significantly higher while TGF-β1 expression at T1-4 was significantly higher in group N2 than in group N1. The inflammatory changes of the lung tissue were significantly ameliorated in group N1 and N2 as compared with control group. Conclusion NAC can attenuate CPB- induced lung injury through down-regulatlng TGF-β1 expression and inflammatory response of the lung tissue.