金水宝对哮喘大鼠气道重塑、气道炎症及氧化应激水平影响的研究

The Effects of Jinshuibao on Airway Remodeling,Airway Inflammation and Oxidative Stress Level in Asthmatic Rats

目的探讨金水宝对支气管哮喘大鼠气道重塑、气道炎症及氧化应激水平的影响。方法以卵蛋白为过敏原致敏和激发,建立大鼠慢性哮喘气道重塑的模型。将40只实验大鼠随机分为5组:对照组(A组)、哮喘组(B组)、布地奈德组(C组)、金水宝正常剂量组[D组,310mg/(kg.d)]、金水宝高剂量组[E组,620mg/(kg.d)],每组8只。造模5周后行药物干预。造模12周时观察指标:肺泡灌洗液(bronchoalveolar lavage fluid,BALF)的细胞计数与分类,②肺组织转化生长因子-β1(TGF-β1)含量、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力测定,③肺组织病理观察:进行支气管周围炎细胞浸润及杯状细胞增殖评分,测定支气管壁的平滑肌面积、胶原沉积面积,及肺组织TGF-β1的积分光密度值(IOD值)。结果A、C、D、E组的气道重塑指标与B组比较差异均有显著性(均P<0.01或P<0.05),以E组改善最明显,且E组降低氧化应激水平、气道炎症指标亦最明显。相关性分析表明:SOD活性与MDA含量呈负相关(r=-0.869,P<0.01),支气管壁的胶原沉积面积与MDA含量、BALF的中性粒细胞计数均呈正相关(r=0.594,P<0.01或r=0.414,P<0.01)。结论氧化应激是哮喘气道重塑产生的机制之一。金水宝可能通过清除氧自由基,减少气道炎症(特别是中性粒细胞)及氧化应激水平,而改善或延缓气道重塑的发生。金水宝高剂量比布地奈德能更好地延缓哮喘气道重塑的发生。

Objeetive To analyze the effects of Jinshuibao on airway remodeling, airway inflammation and oxidative stress level in asthmatic rats. Methods Using ovalbumin as allergens sensitized and stirred, established chronic asthma airway remodeling of rat model. Forty rats randomly divided into 5 groups： control group （group A）, asthma group （group B）, budesonide group （group C）,Jinshuibao the normal dose group[groups D,310 mg/（kg·d）],Jinshuibao at high-dose grouprgroup E,620 mg/（kg·d）3. Each group consisted of 8 rats. Drug intervention group were intervened by drugs after model five weeks. The rats in each group were be observed at 12 weeks after model was established： （1）detection cell count and classification of lung lavage fluid （bronchoalveolar lavage fluid, BALF）.（2）lung tissue TGF-β1 content, malondialdehyde （MDA）content, superoxide dismutase （SOD）vitality determination. （3）observation of lung histopathology：to score bronchial around inflammatory cell infiltration and goblet cell proliferation,determination smooth muscle area, collagen deposition area in bronchial wall, as well as TGF-β1 Immun-ohistochemical expression of the integral optical density （IOD values） in lung tissue. Resuits The indicators of airway remodeling in groups A,C,D,E were significantly different from that in group B（P〈0.01 or P〈0.05） ;Improvements in group E was the most obvious. The levels of oxidative stress and indicator of airway inflammation in group E reduced most obvious. Correlation analysis showed that SOD activity and MDA content were good negative correlations （r=0. 869,P〈0. 01）, bronchial wall collagen deposition area compared with MDA content and the BALF neutrophil count were good positively correlated （r=0. 594, P〈0.01 or r = 0. 414, P〈0.01）. Conclusion Oxidative stress is generated one of the mechanisms on airway remodeling. Jinshuibao maybe through scavenging oxygen free radicals,reduce airway inflammation（the particular of neutrophil）and the level of oxidative stress,which improve or delay the occurrence of airway remodeling. Jinshuibao at high-dose is better than budesonide to postpone the occurrence of asthma airway remodeling.