摘要
目的 观察双氢青蒿素对小鼠百草枯（PQ）中毒的治疗作用及其机制.方法 成年昆明小鼠220只,随机分为空白对照组（A组）、模型组（PQ组）、强的松干预组（CS组）、双氢青蒿素干预组（DHA组）各55只.PQ、CS、DHA组按100 mg/kg给予百草枯灌胃造模.A组予等量的蒸馏水.2 h后开始药物干预,CS组予6 mg/kg强的松灌胃,DHA组予20 mg/kg双氢青蒿素,余各组在相同条件下予蒸馏水.后每天于同样时间点予相同方法药物干预.观察动物中毒反应,并于观察点（第3、7、14、21天）随机处死各组存活的动物8只,计算肺系数、观察肺组织病理变化（HE和Masson染色）及测定肺组织匀浆中肿瘤坏死因子-α（TNF-α）含量.结果 ①PQ、CS、DHA组体质量早期减少后增加,DHA组增加较PQ、CS明显（P〈0.05）.②4~7 d各组间小鼠死亡率比较（χ2=21.439,P〈0.042）、PQ与DHA比较（χ2=5.026,P〈0.042）差异均有统计学意义.③PQ、CS、DHA组肺系数随时间推移减轻,但PQ组第3、7天明显高于正常组（P〈0.05）.④各组早期出现肺水肿、肺泡炎症表现,后期则胶原增生、肺泡壁增厚.DHA较PQ、CS降低了肺纤维化程度.⑤TNF-α在PQ组升高趋势最明显,第7、14天均高于余下三组（P〈0.05）;DHA组上升趋势较CS组弱,第7、14天低于PQ、CS组（P〈0.05）.结论 双氢青蒿素对小鼠PQ中毒及其所致肺纤维化有防治作用,抑制肺组织TNF-α的表达可能是其机制之一.
Objective To study the curative effects of dihydroartemisinin on pulmonary fibrosis induced by paraquat in mice and its mechanism. Methods A total of 220 mice were randomly divided into blank control group （Group A）, model group （PQ group ）, prednisone treatment group （CS group）, and dihydroartemisinin treatment group （DHA Group）. The PQ, cs, DHA group were ingavaged with 100 mg/kg Paraquat. Group A was given equivalent distilled water. Two hours later, prednisone （6 mg/kg） was administered to the mice in CS group once a day, while DHA group was cured by intragastric administration of 20 mg/kg DHA, the other two groups were given equivalent distilled water once a day under the same conditions. Toxic reactions of the mice were observed, and at the 3rd, 7th, 14th and 21st day, 8 mice of each group were randomly sacrificed to calculate lung coefficient, and to detect morphology changes and TNF - o~ levels in the lung tissues. Results @The body weight of PQ, CS, DHA group were decreased at the earlier stage and then increased, but the body weight of DHA group was increased more rapidly than that of PQ and CS group at the later stage with a significant difference （ P 〈 0.05）. @The chi - square of mortalityfrom the 4th day to 7th day among the four groups was 21.439 （P 〈0. 042）, while the chi -square between group DHA and group PQ was 5.026 （P 〈 0.042）, and the differences were significant. @Lung coefficient of PQ, CS and DHA group was reduced gradually during the experimental period, but the lung coefficient of PQ group was significantly higher than that of control group （P 〈 0.05 ） at the 3rd and 7th day. @Pulmonary edema, hemorrhage or extrusion of inflammatory cells were seen in all groups at the earlier stage, and fibroblasts proliferation, alveolar wall thickening appeared at the later stage. The lung inflammation and fibrosis was relieved by dihydroartemisinin treatment compared with the PQ group and CS group. @The rise trend of the level of TNF - α in PQ group was the most obvious, and at the 7th and 14th day the TNF - α level was higher than the normal group, CS group and DHA group （P 〈 0.05） ; The rise trend of the DHA group was relatively slower, and the level of TNF - α was lower than that of PQ and CS groups （ P 〈 0. 05） at the 7th and 14th day. Conclusion Dihydroartemisinin has preventive or curative effects on paraquat poisoning and pulmonary fibrosis induced by paraquat. Suppressing the expression of TNF - α in lung tissues may be one of the probable mechanisms.
出处
《中国急救医学》
CAS
CSCD
北大核心
2013年第10期889-893,I0001,共6页
Chinese Journal of Critical Care Medicine
