紫草素对脂多糖诱导的小鼠肺损伤的保护作用  

Protective Effects of Shikonin on Lipopolysaccharide Induced Lung Injury in Mice

作　　者：白光振 张成生[2] 陈鹏 张峰 张旭[2] 雷杰 Bai Guangzhen;Zhang Chengsheng;Chen Peng(Department of Thoracic Surgery,Tangdu Hospital,The Fourth Military Medical University,Shaanxi 710038,China)

机构地区：[1]空军军医大学(第四军医大学)唐都医院胸外科,西安710038 [2]中国人民解放军第二九一医院外科,包头014030 [3]空军军医大学(第四军医大学)唐都医院肿瘤科,西安710038

出　　处：《医学研究杂志》2018年第10期64-68,共5页Journal of Medical Research

基　　金：内蒙古自治区自然科学基金资助项目(2017BS0818);内蒙古自治区卫生计生科研计划项目(201703261)

摘　　要：目的研究紫草素在小鼠ALI中的作用与机制,为ALI的药物治疗提供新的思路。方法将BALB/c小鼠分成空白对照组、紫草素组、LPS组和LPS+紫草素组,小鼠气管内滴入LPS(5mg/kg)之前1h,预先通过灌胃法给予小鼠50mg/kg剂量的紫草素或其溶剂。LPS给药6h后采集肺泡灌洗液(BALF)及肺组织,用ELISA法检测BALF中TNF-α和IL-1β的浓度,BCA法测定BALF中蛋白浓度;肺组织行病理组织切片检查,测定肺湿干重比,比色法检测组织匀浆液中MPO活性及NO浓度,Western blot法检测肺组织中诱生型一氧化氮合成酶(i NOS)的表达水平。对上述结果进行分析,研究紫草素在ALI小鼠体内的抗炎作用与机制。结果检测BALF中TNF-α和IL-1β的浓度以及BALF中的蛋白含量发现,紫草素+LPS组的浓度较LPS组显著降低,差异有统计学意义(P <0. 05)。比色法测定肺组织中MPO活性和NO浓度发现,紫草素+LPS组也明显低于LPS组,差异有统计学意义(P <0. 05)。紫草素预处理组的肺湿干重比也较LPS组明显降低,差异有统计学意义(P <0. 05)。此外,紫草素预处理组的肺组织病理学改变也较LPS组有所减轻,尤其体现在肺组织炎性细胞的浸润明显减少。Western blot法检测显示,紫草素+LPS组的i NOS表达量较LPS组明显下降,差异有统计学意义(P <0. 05)。结论紫草素可在病理学改变、减轻肺水肿、减少炎性因子的释放和中性粒细胞的浸润等多方面缓解ALI。这种保护作用的潜在机制可能与紫草素抑制i NOS有关。Objective To investigate the role of shikonin in acute lung injury(ALI)induced by lipopolysaccharide(LPS)in mice.Methods Forty male BALB/c mice were randomly allocated into 4 groups(n=10,each):control group,shikonin group,LPS group,and LPS+shikonin group.Shikonin(50mg/kg)or vehicle was given with an intragastric administration 1 hour before intratracheal instillation of LPS(5mg/kg).The severity of pulmonary injury was evaluated 6 hours after LPS challenge.Results Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathological changes,alveolar hemorrhage and neutrophil infiltration.The lung wet/dry weight ratios,as the index of pulmonary edema,were markedly decreased by shikonin pretreatment.Moreover,Shikonin decreased the productions of the pro-inflammatory cytokines tumor necrosis factor(TNF)-αand interleukin(IL)-1βand the concentration of total proteins in the bronchoalveolar lavage fluid(BALF).Shikonin pretreatment also reduced the concentrations of myeloperoxidase(MPO)and nitric oxide(NO)in lung tissues.In addition,shikonin pretreatment significantly suppressed LPS-induced activation of inducible nitric oxide synthase(iNOS)in lung tissues.Conclusion This study provides evidence that shikonin has a protective effect against LPS-induced ALI,and the potential mechanism of this action may attribute partly to the inhibition of iNOS.

关 键 词：紫草素 脂多糖 肺损伤 诱生型一氧化氮合成酶(iNOS) 

分 类 号：R563.9[医药卫生—呼吸系统] R974[医药卫生—内科学]