摘要
目的探讨双氢青蒿素对大鼠肺组织纤维化的干预作用和机制。方法将75只SD大鼠随机分为对照组、模型组、双氢青蒿素高剂量组、双氢青蒿素低剂量组和强的松组，每组各15只。对照组气管内注入9g／L盐水0．3mL，其余4组气管内注入博来霉素（3mg／kg），对照组和模型组每天予9g／L盐水3mL灌胃，双氢青蒿素高、低剂量组每天分别予双氢青蒿素（100、50ms／kg）灌胃，强的松组每天予5mg／kg强的松灌胃。各组分别于第8、15、29天处死5只大鼠取肺组织，以HE染色观察肺组织的炎症程度，Masson染色观察肺组织内胶原沉积情况，以免疫组织化学法检测转化生长因子p1（TGF—β1）、Ⅰ型胶原、Ⅲ型胶原在肺组织中的表达。结果双氢青蒿素高、低剂量组及强的松组肺组织炎症较模型组轻。8、15、29d时，模型组胶原面积均明显高于对照组（P均〈0．01），而双氢青蒿素高、低剂量组及强的松组均明显低于模型组（P均〈0．01），但均高于对照组（P均〈0．01）；双氢青蒿素高剂量组与强的松组各时间点比较差异无统计学意义（P〉0．05）。双氢青蒿素低剂量组胶原面积均明显高于双氢青蒿素高剂量组和强的松组（P均〈0．01）。8、15、29d时，模型组肺组织TGF-β1、Ⅰ型胶原、Ⅲ型胶原表达较对照组均明显升高（P均〈0．01）；双氢青蒿素高剂量组、强的松组肺组织TGF—G1、Ⅰ型胶原、Ⅲ型胶原均明显低于模型组（P均〈0．01），但仍明显高于对照组（P均〈0．01）。除29d时双氢青蒿素高剂量组Ⅲ型胶原的表达低于强的松组（P〈0．叭），其余时间点双氢青蒿素高剂量组肺组织TGF-β1、I型胶原、Ⅲ型胶原与强的松组比较，差异均无统计学意义（P均〉0．05）。结论1．双氢青蒿素可减轻大鼠肺纤维化程度。2．双氢青蒿素的抗纤维化作用有剂量依赖性。3．双氢青蒿素可能通过抑制TGF—β1在肺组织的表达进而减少Ⅰ型、Ⅲ型胶原在肺组织的沉积而起抗肺组织纤维化的作用。
Objective To investigate the effect of dihydroartemisinin on pulmonary fibrosis and its mechanism in rats. Methods Seventy-five SD rats were randomly divided into 5 groups ： the control group, the model group, the high dibydroartemisinin group, the low dihydroartemisinin group, and the prednisone group （15 rats in each group）. Saline （9 g/L, 0.3 mL ）was injected into the rat trachea of the control group, and the rats of the rest 4 groups were injected bleomycin（3 mg/kg）. The rats in the control group and the model group received saline lavage （ 9 g/L, 3 mL）, while the rats in the high dihydroartemi-sinin group and the low dihydroartemisinin group received dihydroartemisinin lavage （ 100, 50 mg/kg）, and the rats in the prednisone group received prednisone lavage each day. Five rats in each group were sacrificed and lung tissues were removed on the 8th, 15th, and 29th day of lavage, and the degree of inflammation in lung tissue was observed by HE staining. The deposit of collagen in lung tissue was observed by Masson staining. The expressions of transforming growth factor 131 （TGF-β1）, collagen Ⅰ and collagen Ⅲ in pneumonic tissues were detected by immunohistochemistry. Results The degree of inflammation in pneumonic tissues in the high dihydroartemisinin group, the low dihydroartemisinin group, and the prednisone group were less significantly than that in the model group（ all P 〈 0.01 ）. The deposit of collagen in lung tissues in the model group was obviously increased than that of the control group at each time points（ all P 〈 0.01 ）. The deposit of collagen in lung tissues in the high dihydroartemisinin group, the low dihydroartemisinin group and the prednisone group were lower than that in the model group（ all P 〈0.01 ）, and higher than that of the control group at each time points（ all P 〈0. O1 ）. There was no significant difference between the high dihydroartemisinin group and the prednisone group （ P 〉 0.05 ）. TGF-β1, collagen Ⅰ and collagen Ⅲ in lung tissues in the high dihydroartemisinin group and the prednisone group were lower than those in the model group（ P 〈 0. O1 ）, and higher than those in the control group at each time points （ all P 〈 O. 01 ）. There was no significant difference in TGF-β1, collagen Ⅰ and collagen Ⅲ in lung tissue between the high dihydroartemisinin group and the prednisone group （ all P 〉 O. 05 ）, except that collagen Ⅲ expression in lung tissues was lower than that of the prednisone group on the 294 day（ P 〉 0.05 ）. Conclusions Dihydroartemisinin can lessen the extent of pulmonaryfibrosis in rats and its anti-fibrosis effect is dose-dependent. The anti-fibrosis effect of dihydroartemisinin may decrease the deposit of collagens in the lung tissues by inhibiting TGF-β1 expression in the lung tissues and have an effect of antifibrosis.
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2013年第16期1253-1256,共4页
Chinese Journal of Applied Clinical Pediatrics
基金
河南省卫生厅资助项目（200804056）
作者简介
通信作者：王静，Email：wangjing@zzu．edu．en
