姜黄素对矽肺纤维化的防治作用及其机制研究
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摘要
目的
     建立小鼠矽肺纤维化动物模型,经灌胃给予不同剂量姜黄素,旨在研究
     1.体内实验观察姜黄素对小鼠矽肺纤维化的影响。
     2.姜黄素对矽肺纤维化小鼠模型血清和肺匀浆中TNF-α、TGF-β1含量的影响。
     方法
     1.采用经气管一次性大量注入二氧化硅(SiO2)粉尘悬液建立小鼠矽肺模型,并给予不同剂量姜黄素灌胃。实验设假手术组、SiO2模型组、姜黄素高、中、低剂量治疗组,共五组。手术后两周各治疗组开始给药。
     2.术后四周、八周,各组分别摘眼球取血,离心取血清;然后取肺组织。
     3.病理形态学观察:HE染色用于观察肺部病理改变;MASSON染色显示胶原纤维的沉积情况以判定肺部纤维化程度。并采用图象分析系统,进行定量分析。
     4.反应纤维化肺组织细胞损伤程度相关生化指标的测定:分别测定血清和肺匀浆中,肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、转化生长因子-β1(transforminggrowth factor-β1,TGF-β1)的含量。
     5.统计学处理:用统计学软件SPSS13.0进行分析。各组均数比较采用单因素方差分析(one-way ANOVA),P<0.05表示有统计学意义;EXCEL软件绘图。
     结果
     1.成功建立了小鼠矽肺纤维化模型。
     2.小鼠吸入SiO2粉尘后,模型组肺脏有了明显损伤且肺脏内胶原纤维合成增加;与假手术组比较,肺组织匀浆、血清中TGF-β、TNF-α含量均显著升高(P<0.01)。
     3.给予姜黄素后,病理形态学观察及图象分析显示,小鼠肺脏损伤及肺脏纤维化程度减轻,给予低、中、高剂量的姜黄素组,都可以一定程度改善矽肺小鼠肺脏受损的状况。
     4.给予姜黄素后,可以不同程度地降低肺组织匀浆以及血清中TGF-β1、TNF-α的含量(P<0.05)。姜黄素的剂量和作用时间与TGF-β1、TNF-α含量呈一定程度的负相关性。
     结论
     1.姜黄素能明显减轻肺脏的损伤,改善实验性矽肺纤维化。
     2.姜黄素能降低实验性矽肺纤维化小鼠肺组织及血清中TGF-β1、TNF-α的含量。
     3.姜黄素对矽肺纤维化有一定程度的治疗作用,可能与其降低TGF-β1、TNF-α的含量有关。
OBJECTIVE
     The aim of this study was to investigate the effect and mechanism of curcumin in the pathogenesis of silicosis fibrosis in mice
     METHODS
     1.To establish the model of silicosis fibrosis in mice with SiO2.
     2.Histochemical staining:
     The mice were killed on the day of 28 and 56 after SiO2 administration,and their lung were cut off and embedded with formalin,then the pathological changes and the deposition of collagen in lung were observed by HE,MASSON staining.
     3.The indexes about fibrosis were detected through transforming growth factor-β1(TGF-β1) and tumor necrosis factor-α(TNF-α).
     4.Imaging analysis system
     HE,MASSON staining were quantitated by medical imaging analysis system.
     5.Statistics analysis
     Compare between two different groups at the same phase by T test.All statistical analyses were performed by using the software of SPSS 13.0.The plots were done with Microsoft EXCEL software.
     RESULTS
     1.Murine silicosis fibrosis model was built successfully.
     2.The lung was damaged,and deposition of collagen increased after infection.The degree of silicosis fibrosis is lower in curcumin group.
     3.The levels of TGF-β1 and TNF-αin serum and lung were lower than those in infection control group significantly(P<0.05 or P<0.01).
     CONCLUSION
     1.In a certain extent,curcumin can lessen the content of the impaired lung and cut down the degree of silicosis fibrosis.
     2.Curcumin can lower expression TGF-β1 and TNF-αin serum and lung.
     3.Curcumin has the function of protecting lung cells and anti-pulmonary fibrosis induced by SiO2 in mice.That may be related to lower expression TGF-β1 and TNF-α.
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