| 摘要: |
| 目的 研究穿心莲内酯对脓毒症小鼠的保护作用及相关机制。方法 采用盲肠结扎穿孔(CLP)法制作小鼠脓毒症模型。64只C57BL/6小鼠随机均分为4组: 假手术组(sham组)、脓毒症模型组(CLP组)、二甲亚砜组(DMSO组)和穿心莲内酯组(AND组)。各组小鼠于术后1、6、12 h腹腔内分别注射相同剂量(0.2 mL)的生理盐水、5% DMSO或穿心莲内酯(10 mg/kg),记录各组小鼠术后7 d生存率并绘制生存曲线。另取48只C57BL/6小鼠,分组及给药方法同前,术后24 h分别检测腹腔灌洗液(PLF)中性粒细胞(PMN)数量、外周血及PLF细菌负荷以及外周血炎症因子TNF-α、IL-6、IL-10水平,同时取小鼠肺脏及肝脏组织进行病理分析。结果 与CLP组相比,AND组小鼠术后7 d生存率增加(P<0.01),腹腔PMN计数下降(P<0.01),外周血和腹腔细菌清除能力增强(P<0.01),外周血TNF-α、IL-6水平降低,而IL-10水平升高(P<0.01),肺组织和肝脏组织病理损伤程度减轻(P<0.01)。DMSO组与CLP组各项检测指标差异均无统计学意义。结论 穿心莲内酯对CLP脓毒症小鼠具有保护作用,可能与其调节免疫功能,增强细菌清除能力以及降低过度炎症反应有关。 |
| 关键词: 穿心莲内酯 脓毒症 存活率分析 中性白细胞 炎症因子类 |
| DOI： |
| 投稿时间：2013-03-08修订日期：2013-05-23 |
| 基金项目: |
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| Protective effects of andrographolide on septic mice and the related mechanism |
| ZHAO Zhen-zhen,WANG Jun,ZHU Wei-min,LIU Yi,LI Jin-bao,DENG Xiao-ming* |
(Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*Corresponding author.) |
| Abstract: |
| Objective To investigate the protective effects of andrographolide on septic mice and to explore the underlying mechanism. Methods Sepsis model was induced by cecal ligation and puncture (CLP) in mice. A total of 64 C57BL/6 mice were evenly randomized into 4 groups: a sham group, a CLP group, a dimethyl sulfoxide (DMSO) group and an andrographolide (AND) group. The mice were injected intraperitoneally with 0.2 mL normal saline, 0.2 mL 5% DMSO or 0.2 mL andrographolide (10 mg/kg) at 1 h, 6 h and 12 h after surgery. The survival rates were assessed 7 days after surgery and the survival curve was plotted. Another 48 C57BL/6 mice were grouped as above. The peripheral blood, peritoneal lavage fluid (PLF), lung and liver tissues were harvested 24 h after operation. Polymorphonuclear leukocyte (PMN) count in PLF was determined. Bacterial loads in the peripheral blood sample and PLF were also determined. The levels of TNF-α, IL-6 and IL-10 in the blood samples were detected by ELISA. The lung and liver tissues were observed and analyzed by hematoxylin-eosin staining. Results Compared with CLP group, AND group had a significantly increased survival rate 7 days after operation (P<0.01), a significantly decreased PMN count in PLF (P<0.01), a significantly enhanced bacterial clearance capability in both blood and PLF (P<0.01), significantly decreased serum TNF-α and IL-6 levels, significantly increased IL-10 level, and significantly alleviated lung and liver tissue injuries (P<0.01). The above parameters were not significantly different between the DMSO group and CLP group. Conclusion Andrographolide has protective effect against CLP-induced sepsis in mice, which might be associated with regulation of the immunological function, enhancement of bacterial clearance and inhibition of excessive inflammatory response during sepsis. |
| Key words: andrographolide sepsis survival analysis neutrophils inflammatory factors |
