N-乙酰半胱氨酸对博莱霉素大鼠肺脏氧化-还原状态的影响

Effects of N-Acetylcysteine on Oxidative-Redox Status and Deposition of Extracellular Matrix in Bleomycin-induced Pulmonary Fibrosis in Rats

目的 :探讨肺脏氧化 -还原状态与肺脏炎症、肺纤维化的关系及N 乙酰半胱氨酸对肺纤维化的影响。方法 :健康雌性Wistar大白鼠经支气管灌注博莱霉素 (BLM )造成肺间质纤维化。部分灌注BLM后每日腹腔注射N 乙酰半胱氨酸 (NAC) 4 0mg/kg。计数支气管肺泡灌洗液 (BALF)中细胞总分数 ,检测血清和BALF中谷胱甘肽(GSH)、丙二醛 (MDA)的含量。肺组织制成石蜡切片行HE染色进行病理和炎症积分分析。左肺匀浆后测羟脯氨酸 (HYP)含量。结果 :BLM组急性炎症期BALF细胞总数显著增高 ,中性粒细胞 (PMN)、淋巴细胞百分比显著增高 ,肺组织炎症积分增加 ,14d时HYP含量较对照组显著增加 (P <0 .0 5 ) ;NAC能够降低急性期BALF中细胞总数、PMN和淋巴细胞百分比 ,但在纤维化期细胞总数有所增加。NAC组肺组织炎症积分下降 ,但HYP含量较BLM组略增加 ;各组血清GSH和MDA水平无显著差异 ;BLM组BALFGSH水平第 17天显著降低 ,NAC能够显著提高BALFGSH水平。结论 :BALFGSH ,MDA水平较血清GSH ,MDA水平能更好的反映肺脏损伤情况和对治疗的反应 ;NAC(40mg/kg)能够减少肺组织炎症细胞的浸润和BALF中中性粒细胞百分比 ,表明小剂量NAC具有一定的抗炎作用 ,但其对肺纤维化大鼠胶原沉积无保护作用。

Objective: Our aim was to investigate the relationship between the oxidative redox status and pulmonary fibrosis, and the effects of N acetylcysteine(NAC) on bleomycin induced pulmonary fibrosis in rats. Methods: Wistar rats received bleomycin (5mg/kg in 0.2ml saline) via trachea. The NAC (40mg/kg·d) was injected intraperitoneally after bleomycin(BLM) instillation. Control rats received normal saline. The numbers of total cells and differentia ratio of BALF, the numbers of inflammatory cells in lung tissue, levels of reduced glutathione (GSH) and malonyldialdehyde (MDA) in serum and BALF, hydroxyproline (HYP) in lung tissues were determined on the 1,3,7,14,28 day. Results: N acetylcysteine decreased the percentage of inflammatory cells in BALF and lung tissues during the stage of alveolarlitis. No significant change was found in serum levels of GSH and MDA between rats received different treatments. Levels of GSH increased and levels of MDA decreased in BALF on the 1,3,7 day (P<0.01) in NAC treated group. Levels of HYP in bleomycin treated lungs significantly increased on the 14 and 28 day compared with the sham group (P<0.05), and levels of HYP in NAC group were higher than those in bleomycin group from the 7 day to 28 day,but had no significance. Conclusion: Levels of GSH and MDA in BALF might be indicators to reflect status of oxidative stress in lung. Treatment with NAC(40mg/kg) could decrease the inflammatory cells infiltration in BLM induced pulmonary fibrosis, but have no protective effect on the collagen deposition.