摘要
目的 探寻丹参酮ⅡA对脓毒症肺血管内皮细胞损伤的保护作用.方法 采用盲肠结扎穿孔术构建脓毒症肺损伤小鼠模型,分为6组:假手术组、模型组、丹参酮1组(10 mg/kg)、丹参酮2组(30 mg/kg)、丹参酮3组(50 mg/kg)、丹参酮4组(100 mg/kg).药物干预24 h后检测肺组织病理变化、肺微血管通透性、肺组织湿/干重比、白细胞计数以及炎症因子等各项指标,假手术组仅行盲肠探查术.结果 丹参酮各组较模型组小鼠肺组织损伤及评分均减轻(P＜0.05).与模型组比较,丹参酮各组小鼠肺组织Evans Blue含量、肺组织湿/干比明显降低(P＜0.05),BALF白细胞计数、蛋白含量、炎症因子明显减少(均P＜0.05),且呈剂量依赖性,其中丹参酮2组、丹参酮3组和丹参酮4组之间,肺组织病理损伤、Evans Blue含量、肺组织湿/干比以及肺泡灌洗液中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)表达水平差异无统计学意义(均P＞0.05).结论 丹参酮ⅡA能够剂量依赖性地降低脓毒症所致的肺微血管内皮细胞损伤,从而改善肺损伤;30 mg/kg剂量的丹参酮Ⅱ A即可达到最佳效果.
Abstract
Objective:To explore the protective effect of Tanshinone Ⅱ A(Tan Ⅱ A)on endothelial cell injury in septic pulmonary vasculature.Methods:A mouse model of septic lung injury was constructed using cecal ligation and puncture(CLP).Mice were divided into six groups:sham operation group,model group,experimental group 1[CLP+10 mg/kg Tan ⅡA],experimental group 2[CLP+30 mg/kg Tan Ⅱ A],experimental group 3[CLP+50 mg/kg Tan Ⅱ A],and experimental group 4[CLP+100 mg/kg Tan Ⅱ A].After 24 hours of treatment,various indicators such as lung tissue pathology,pulmonary microvascular permeability,lung tissue wet/dry weight ratio,white blood cell count,and inflammatory factors were measured.The sham group underwent only cecal exploration.Results:The experimental groups showed reduced lung tissue injury and scores compared with the model group(P＜0.05).Compared with the model group,the experimental groups exhibited significantly lower Evans Blue content and lung tissue wet/dry weight ratio(P＜0.05).Compared with the model group,the experimental groups had signifi-candy reduced white blood cell count,protein content,and inflammatory factors in bronchoalveolar lavage fluid,with statistically significant differences(all P＜0.05).There were no significant differences in lung tissue pathologi-cal damage,Evans Blue content,lung tissue wet/dry weight ratio,and the expression levels of IL-6,TNF-α,IL-1β,and other inflammatory factors in bronchoalveolar lavage fluid among experimental group 2,experimental group 3,and experimental group 4(all P＞0.05).Conclusion:Tan ⅡA can dose-dependently reduce endothelial cell inju-ry in septic pulmonary microvasculature,thus improving lung injury,and 30 mg/kg Tan ⅡA can achieve the best ef-fect.
基金项目
湖北省病理生理学会科研项目(2021HBAP002)
湖北省自然科学基金(2021CFB026)
中央财政医疗服务能力建设、卫生健康人才培养项目(新财社[2022]255号)
深圳市南山区科技计划重点项目(NS2022014)
吴阶平医学基金会临床科研专项(320.6750.2021-11-12)
NETL
NSTL
万方数据