摘要
目的观察青蒿素对脓毒症大鼠的保护作用并探讨其作用机制。方法采用盲肠结扎穿孔术(cecal ligationand puncture,CLP)制作大鼠脓毒症模型,观察青蒿素对CLP大鼠死亡率的影响,ELISA法检测术后2、6、12、24、48和72 h大鼠血清LPS、TNF-α和IL-6水平;光镜和透射电镜观察72 h大鼠肠粘膜形态学的变化;分离大鼠腹腔巨噬细胞(PMΦ),ELISA法检测青蒿素对LPS(100 ng/m l)及热灭活大肠杆菌(3.5×107CFU/m l)刺激PMΦ释放TNF-α及IL-6的影响。结果青蒿素组大鼠死亡率低于模型组(P<0.05),CLP术后血清LPS、TNF-α和IL-6水平较模型组降低(P<0.05或P<0.01),肠粘膜的损伤程度减轻;青蒿素对LPS和热灭活大肠杆菌刺激PMΦ释放TNF-α和IL-6具有显著的抑制作用并呈量效关系(P<0.01)。结论青蒿素能抑制CLP大鼠巨噬细胞活化并减轻肠粘膜损伤,对CLP大鼠具有保护作用。
Objective To investigate the biological activity and mechanism of artemisinin on septic rats. Methods Septic model was established by cecal ligation and puncture （CLP） in Wistar rats. Artemisinin was administrated to observed its protective effects on septic rats. Blood was collected to examine serum lipopolysaccharide （LPS）, TNF-α and IL-6 after 2, 4, 6, 12, 24, 48 and 72 h by kinetic turbidimetric limulus test and ELISA. The morphological changes of intestinal mucosa were observed with light microscope and transmission electron microscope. The peritoneal macrophages （PMΦ） in rats were isolated and the release of TNF-α and IL- 6 in PMΦ after exposure to LPS （ 100 ng/ml） and heat-killed E.coli were detected by ELISA. Results Mortality in the artemisinin group was significantly lower than the septic group （ P 〈 0. 05 ）. The concentrations of LPS, TNF-α and IL-6 in serum were significantly lower in the artemisinin group （P 〈 0. 05 or P 〈 0. 01 ）. The degree of inflammatory injury of intestinal mucosa was much milder in the artemisinin group than in the septic group. In addition, artemisinin could inhibit remarkably the release of TNF-α and IL-6 in LPS-stimulated and heat-killed E. coli PMΦ of rats in vitro （ P 〈 0. 05 or P 〈 0. 01 ）. Conclusion Artemisinin protects the septic rats by inhibiting the release of cytokines.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2005年第17期1769-1772,共4页
Journal of Third Military Medical University
