亚细亚酸对兔未成熟肺缺血再灌注损伤的保护作用

目的 观察亚细亚酸对兔未成熟肺缺血再灌注损伤的保护作用。方法 选用15~21日龄新西兰白兔60只，分为5组：假手术组，对照组，亚细亚酸低、中和高剂量组，每组各12只。建立单肺缺血再灌注模型，肺门阻断1 h后，开放再灌注4 h。亚细亚酸低、中和高剂量组分别于术前3 d给予亚细亚酸7.5、15和30 mg·kg-1,假手术组仅开胸不阻断肺门，对照组不予干预。术毕收集肺组织，光镜和电镜观察肺组织病理和超微结构改变。测定肺组织丙二醛（MDA），细胞毒性活性氧（ROS）-HR、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）水平。Western Blot检测髓样生化因子（MyD）88和核转录因子（NF-κB）水平。ELISA法检测IL-1β、TNF-α水平。结果 ①亚细亚酸中和高剂量组肺缺血再灌注损伤明显减轻，光镜下肺泡与肺泡间隔肿胀程度明显轻于对照组，肺泡腔渗液减少，出血少见。电镜下可见肺泡上皮与血管内皮细胞脱落明显减少。②亚细亚酸中和高剂量组较对照组肺组织MDA，ROS-HR水平明显降低，SOD及GSH-PX水平明显升高；各时点的IL-1β、TNF-α水平也有不同程度下降，特别是再灌注后的2 h和4 h(P<0.05)；肺组织中MyD88和NF-κB表达显著下降。③亚细亚酸中和高剂量的保护效果较好。结论 亚细亚酸对未成熟肺缺血再灌注损伤有一定的保护作用，其机制与清除氧自由基和减轻全身炎性反应有关。

Human coronavirus and infection of respiratory tract

Objective The aim of the study was to examine whether asiatic acid could attenuate ischemia-reperfusion(I/R) induced lung injury in infant rabbits. Methods 60 New Zealand white rabbits aged from 15 to 21 days were subjected to sham operation, I/R, low dose asiatic acid plus I/R, medium dose asiatic acid puls IR, and high dose asiatic acid puls I/R. I/R was induced by clamping the right pulmonary hilum for 1 hour and then removal of the clamp for 4 hours. Asiatic acid was given 3 days before operation by 7.5mg, 15, 30 mg·kg-1 respectively. Production and expression of free radical species-hydroxyl radical (ROS-HR), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), myeloid differentiation factor-88(MyD-88), and muclear factors-κB(NF-κB) in the lung tissue were also evaluated. And temperature, hemodynamics, blood gases and neutrophil count were measured 2 hours after reperfusing. In addition, serum levels of interleukin-1β and tumor necrosis factor-α were measured during the ischemia-reperfusion process. Results The infant lungs in asiatic acid middle and high dose groups had less neutrophil infiltration, edema, swelled alveolar epithelial and endothelial cells under light and electron microscopes. ②Compared wtih I/R group, asiatic acid reduced the production of ROS-HR and MDA and improved the activities of GSH-PX and SOD markedly, siginificantly decreased the serum levels of interleukin- 1β and tumor necrosis factor-α at 4 h time point after reperfusion, as well as the MyD88 and NF-κB of lung were siginificantly decreased(P<0.05).③Asiatic acid middle and high dose groups had good effect of attenuating I/R. Conclusions Asiatic acid pretreatment reduced the lung damage induced by I/R in the infant rabbits.