雾化吸人利多卡因对哮喘大鼠肺组织热休克蛋白70、核因子κB表达的影响

Effect of aerosolized lidocaine inhalation on expression of heat shock protein 70 and nuclear factor-kappe B in lung of asthma rat model

目的 观察利多卡因对大鼠支气管哮喘模型肺组织中热休克蛋白70（heat shock protein 70,HSP70）、核因子κB（nuclear factor-kappe B,NF-κB）表达的影响.方法 Wistar大鼠32只,随机分为4组（n=8）：对照组（A组）、哮喘组（B组）、地塞米松组（C组）、利多卡因组（D组）.B组大鼠用鸡卵清蛋白辅以氢氧化铝为佐剂注射致敏,2周后雾化吸入鸡卵清蛋白诱发哮喘;C组、D组大鼠用同样方法致敏,但在激发前分别雾化吸入0.02%地寒米松和0.04%利多卡因20 ml;A组用生理盐水代替鸡卵清蛋白进行注射和吸入.末次雾化吸人后24 h内取肺组织,计算湿十重比（W/D）、观察肺组织病理学改变、免疫组化检测HSP70、NF-κB的表达.结果 ①B、C、D组W/D值分别为4.08±0.16、3.54±0.10和3.66±0.12,和A组3.30±0.12相比增加（P〈0.05）;②B、C、D组肺组织HSP70表达分别为0.210±0.018、0.138±0.010和0.154±0.012,和A组0.049±0.015相比表达上调（P〈0.05）;③B、C、D组肺组织NF-κB表达分别为0.199±0.029、0.132±0.010和0.150±0.017,和A组0.056±0.022相比表达上调（P〈0.05）;④和B组相比,C、D组W/D值、肺组织HSP70、NF-κB的表达下调（P〈0.05）.B组肺组织呈支气管壁增厚、炎性细胞浸润表现.C组、D组病理损伤程度减轻. 结论利多卡因雾化吸入可以减轻致敏原所激发的哮喘大鼠气道炎症和肺组织损伤.

Objective To observe the effect of aerosolized lidocaine inhalation on expression of HSP70 and NF-ΚB in lung of asthma rat model. Methods Thirty two Wistar rats were randomly assigned to four groups （n=8 each）： control group（ group A）, asthma model group（group B）,dexamethasone group（group C）and lidocaine group（group D）. The rats in group B were sensitized by injection of ovalbumin（OA ）together with aluminum hydroxide as adjuvants, followed by aerosolized OA challenge two weeks later. The rats in group C and D were sensitized with OA as group B, but exposed to 0.02% aerosol of dexamethasone and 0.04% aerosol of lidocaine 20 ml respectively. In group A saline was used instead of OA. In 24 hours after the last challenge, the lungs were removed for microscopic examination, determination of W/D lung weight radio, the expression of HSP70 and NF-ΚB was studied immunohistochemically.Results①The W/D lung weight radio were 4.08±0.16,3.54±0.10 and 3.66±0.12 respectively in group B,C,D,more than the group A with 3.30±0.12. ② The pulmonary expression of HSP70 were 0.210±0.018,0.138±0.010 and 0.154±0.012 respectively in group B,C,D, higher than the group A with 0.049±0.015. ③The pulmonary expression of NF -KB were 0.199±0.029,0.132±0.010 and 0.150±0.017respectively in group B, C, D, higher than the group A with 0.056±0.022. ④Compared with the group B, the W/D lung weight radio and pulmonary expression of HSP70 and NF -ΚB in group C and D were significantly down -regulated. In animals with asthma the bronchial walls were significantly thicker with inflammatory cell infiltration. Dexamethasone or lidocaine aerosolized inhalation significantly attenuated the pathologic changes induced by asthma. Conclusion Aerosolized lidocaine inhalation has a protective effect on airway inflammation and histology damages resulting from aeroallergen challenge in the asthma model of Wistar rats.