利多卡因和异丙酚预先给药对哮喘大鼠肺组织NO和内皮素水平的影响

Effects of lidocaine and propofol pretreatment on lung NO and ET levels in a rat model of asthma

目的通过观察预先给予利多卡因和异丙酚对哮喘大鼠内皮素（ET）和一氧化氮（NO）的影响,探讨其对哮喘作用的机制。方法Wistar大鼠32只,随机分为4组（n=8）：对照组（Ⅰ组）、哮喘组（Ⅱ组）、异丙酚组（Ⅲ组）和利多卡因组（Ⅳ组）。Ⅱ组、Ⅲ组、Ⅳ组大鼠用卵清蛋白辅以氢氧化铝注射致敏及雾化吸入诱发哮喘。Ⅲ组、Ⅳ组在诱发前30 min分别从股静脉输注异丙酚50 mg·kg^-1·h^-1或利多卡因12 mg·kg^-1·h^-1。哮喘发作后10 min,采集动脉血行动脉循环内皮细胞（CEC）计数,处死大鼠后,测定支气管肺泡灌洗液（BALF）中ET、NO浓度,计算NO/ET比值;取肺组织,计算肺湿干重比（W/D）、观察肺组织病理学结果。结果与Ⅰ组相比,Ⅱ组、Ⅲ组、Ⅳ组CEC计数及W/D增加,Ⅱ组BALF中ET、NO浓度增高,NO/ET比值下降（P＜0．05）;与Ⅱ组相比,Ⅲ组、Ⅳ组CEC计数及W/D降低, BALF中ET、NO浓度下降,NO/ET比值升高（P＜0．05）。Ⅱ组肺组织呈支气管壁增厚、炎性细胞浸润表现,Ⅲ组、Ⅳ组病理损伤程度减轻。结论利多卡因和异丙酚预先给药可通过降低肺组织ET、NO的水平、调节NO/ET的平衡,减轻了大鼠哮喘的发作程度。

Objective To investigate the effects of lidocaine and propofol pretreatment on asthma in rats and the underlying mechanism. Methods Thirty-two male Wistar rats weighing 160-180 g were randomly divided into4 groups （n = 8 each）： group Ⅰ control; group Ⅱ asthma; group Ⅲ propofol ＋ asthma and group Ⅳ lidocaine ＋ asthma. In group Ⅱ-Ⅳ the animals were sensitized by intraperitoneal injection of egg albumin （OVA） 100 mg mixed with aluminum hydroxide 200 mg in 1 ml. On the 14th day the animals were placed in a semi-closed box and challenged with inhalation of supersonically nebulized OVA for 30 min, once a day × 3 d. Twenty-four hours after the last nebulized OVA inhalation, the animals were challenged with intravenous OVA. In group Ⅲ , Ⅳ the infusion of propofol 50 mg·kg^-1·h^-1 or lidocaine 12 mg·kg^-1·h^-1 was started at 30 rain before the last challenge. In control group normal saline was used instead of OVA. Challenge was considered successful when the animals became restless, short of breath and the abdominal muscle spastically contracted and eventually the extremities became flaccid. Arterial blood samples were collected for determination of the number of circulating endothelial cells （CECs）. The animals were killed 10 rain after the last challenge. The lungs were removed for microscopic examination, determination of W/D lung weight ratio, and determination of NO and ET concentrations and NO/ET ratio in broncho-alveolar lavage fluid （BALF） . Results The NO and ET concentrations were significantly higher and NO/ET ratio was significantly lower in BALF in animals with asthma （groupⅡ） compared with animals in control group （Ⅰ）. Propofol or lidocaine pretreatment significantly attenuated the increase in NO and ET concentrations and decrease in NO/ET ratio in group Ⅲ and 17 as compared with group Ⅱ . There was no significant difference in NO and ET concentrations and NO/ET ratio in BALF among the 2 pretreatment groups （group Ⅲ and Ⅳ）. In animals with asthma the bronchial walls were significantly thicker with inflammatory cell infiltration. Propofol or lidocaine pretreatment significantly attenuated the pathologic changes induced by asthma. Conclusion Pretreatment with lidocaine or propofol can decrease the severity of asthma through regulation of NO and ET levels in the lungs and maintain the balance between NO and ET.