摘要
目的研究脂质体包裹A20及其突变体mA20-ZnF4-7(mA20Δ)质粒对脂多糖(LPS)攻击所致内毒素血症小鼠的治疗作用。方法用LPS攻击小白鼠制备内毒素血症动物模型。随机分为:生理盐水对照组(NS组)、单纯内毒素组、空质粒组、脂质体包裹mA20质粒治疗组(L-mA20组)、脂质体包裹mA20Δ质粒治疗组(L-mA20Δ组)。以ELISA检测各组血浆TNF-α、IL-1β表达,并于12h时间点观察组织病理变化。结果(1)L-mA20组和L-mA20Δ组的TNF-α在各时间点表达(pg/mL)分别为:6h(304.696±6.087)(、304.985±6.291),12h(321.217±10.579)、(256.580±33.524),24h(307.594±11.181)(、280.348±11.698);与单纯内毒素组、空质粒组的TNF-α表达比较有显著性降低(P<0.05)。(2)L-mA20组和L-mA20Δ组的IL-1β在各时间点表达(pg/mL)分别为:6h(256.989±3.921)、(263.655±5.645),12h(205.724±4.827)、(154.690±1.380),24h(165.724±7.772)(、101.816±3.259);依时间有显著性下降趋势;与单纯内毒素组、空质粒组的IL-1β表达比较有显著性降低(P<0.05)。(3)病理观察结果显示:L-mA20组和L-mA20Δ组的肝、肺损伤均较单纯内毒素组、空质粒组轻;与NS相比,肝、肺损伤无明显差别。结论尾静脉注射被脂质体包裹mA20及其突变体mA20-ZnF4-7质粒对内毒素血症小鼠有相似的治疗作用,为临床应用结构更简单的A20蛋白提供了一定实验基础。
Objective To study the therapeutic efficacy of liposome encapsulating mA20 and its mutant mA20-ZnF4-7 plasmid in mice with lipopolysaccharides （LPS） induced endotoxemia. Methods Two prepare the endotoxemia animal model by assaulting mice with LPS（2.5mg/kg）. Forty-five healthy mice weighing 18-20 g were randomized into 5 groups： control group treated with saline（NS group）, LPS group, naked plasmid treated group, liposome encapsulating mA20 plasmid treated group （L-mA20 group） and liposome encapsulating mA20-ZnF4-7 plasmid treated group（L-mA20△ group）. The contents of TNF-α, IL-1β in blood plasma were detected by ELISA. Inflammatory reactions were also observed in pathology. Results （1）The TNF-α expressions（pg/mL） of L-mA20,L-mA20△ groups in every time point were： 6h（304. 696±6. 087）, （304. 985±6. 291） ,12h（321. 217±10. 579）, （256. 580±33. 524） ,24h（307. 594± 11. 181 ）, （280. 348± 11. 698）, which were significantly lower than those of LPS group, naked plasmid treated group （P〈0.05）. （2）The IL-1β expressions（pg/mL） of L-mA20,L-mA20△ groups in every time point were：6h（256. 989 ±3. 921）,（263. 655±5. 645） ,12h（205. 724±4. 827）, （154. 690± 1. 380）,24h（165. 724±7. 772）, （101. 816±3. 259） ;which also significantly lower than those of LPS group and naked plasmid treated group（P〈0.05）. （3） Severe inflammatory damages could be found in LPS group and naked plasmid treated group, but only mild inflammatory changes in L-mA20, L-mA20△ groups There were no histopathological differences among L-mA20,L-mA20△ and NS groups. Conclusion Compared with mA20 plasmid,mA20- ZnF4-7 plasmid transfection in vitro with liposome could obtain similar therapeutic efficacy on experimental endotoxemia, which provided some experimental base for clinical application of A20 protein of more simple construction.
出处
《重庆医学》
CAS
CSCD
2008年第13期1434-1436,1441,共4页
Chongqing medicine
基金
军队"十一五"面上课题资助项目(06MA189)
重庆市科委自然科学基金面上课题资助项目(CSTC2007BB5082)。
