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目的探讨低分子肝素(LMWH)、N-乙酰半胱氨酸(NAC)对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠气道重塑的影响。方法将40只6~8周鼠龄按雌雄各半的SD大鼠分为5组,即健康对照组(C组),熏香烟及脂多糖(LPS)方法制备的COPD模型组(M组),以及低分子肝素(LMWH)注射组(L组)和N-乙酰半胱氨酸(NAC)灌胃组(N组)及前二者同时干预组(LN组);光镜下观察大鼠病理学改变;以图像分析系统测量其支气管壁厚度;偏振光显微镜下观察各组大鼠支气管黏膜下胶原天狼猩红染色的气道胶原沉积。结果①模型制备:本研究制备的COPD模型大鼠支气管、肺病理改变与人类COPD变化基本一致。②支气管壁厚度:与对照组比较,M组、L组、N组和LN组管壁厚度明显增加(P<0.01);而与M组比较,L组、LN组管壁厚度均减少,且以LN组减少最为明显(P<0.01),N组亦有减少但差异无统计学意义(P>0.05)。③胶原沉积:与对照组比较,各组主要呈现Ⅰ型胶原沉积,L组和N组胶原减少,LN组胶原减少更趋明显。结论①较短时间的熏香烟+灌注LPS是建立COPD大鼠模型的简单易行的方法;②LMWH、NAC干预尤其是联合应用可通过不同作用机制减轻COPD发病过程中气道壁厚度及气道胶原沉积,进而减轻COPD气道重塑。
Objective To investigate the effects of LMWH and NAC on airway remodeling in chronic obstructive pulmonary disease (COPD) rats. Methods Forty male and female SD rats aged 6-8 weeks were divided into five groups: healthy control group (C), cigarette smoke and lipopolysaccharide (LPS) (N group), N LM group (N group), and the other two groups (LN group) were treated with low molecular weight heparin (LMWH) injection group (L group) and N-acetylcysteine The pathological changes were observed. The bronchial wall thickness was measured with an image analysis system. The airway collagen deposition in the bronchial submucosal Sirius red staining was observed under a polarized light microscope. Results ①Model preparation: The bronchial and pulmonary pathological changes of COPD model prepared in this study were basically consistent with those of human COPD. ② The thickness of bronchial wall: Compared with the control group, the thickness of the wall of group M, L, N and LN increased significantly (P <0.01), while the thickness of the wall of L and LN decreased LN group decreased the most significant (P <0.01), N group also decreased but the difference was not statistically significant (P> 0.05). ③ collagen deposition: compared with the control group, the group showed mainly type I collagen deposition, collagen L group and N group decreased, LN group decreased more obvious collagen. Conclusion ① Short-term cigarette smoke + perfusion LPS is a simple and easy method to establish COPD rat model. ②LMWH and NAC intervention can reduce the airway wall thickness and airway collagen Deposition, thereby reducing COPD airway remodeling.