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蒙花苷体内外抗肺纤维化作用及其机制研究
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| 篇名： | 蒙花苷体内外抗肺纤维化作用及其机制研究 |
| TITLE： | Study on the anti-pulmonary fibrosis effect of linarin in vivo and in vitro and its mechanism |
| 摘要： | 目的 考察蒙花苷的体内外抗纤维化作用，并初步探讨其作用机制。方法将C57BL/6J小鼠随机分为正常组（羧甲基纤维素钠）、模型组（羧甲基纤维素钠）、阳性对照组（吡非尼酮，200mg/kg）和蒙花苷低、高剂量组（12.5、25mg/kg），每组8只。除正常组外，其余各组小鼠均制备肺纤维化模型。造模结束后，灌胃给药，每天1次，连续14d。观察小鼠一般情况，测定其肺指数，检测其血清中肿瘤坏死因子α（TNF-α）、转化生长因子β（1TGF-β1）水平以及肺组织中白细胞介素6（IL-6）水平；采用苏木素-伊红（HE）染色及Masson染色观察其肺组织病理学变化，并参照Ashcroft评分标准进行肺纤维化评分；检测其肺组织中α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原蛋白（CollagenⅠ）、磷酸化胞外信号调节激酶（p-ERK1/2）、TGF-β1的表达水平。使用TGF-β1刺激人胚肺成纤维细胞HFL1建立体外肺纤维化模型，实验设置正常组、模型组和蒙花苷低、中、高浓度组（3.7、7.4、14.8mg/L），培养48h后，检测细胞中α-SMA、CollagenⅠ、p-ERK1/2蛋白表达水平。结果在体内实验中，与正常组比较，模型组小鼠肺指数和TNF-α、TGF-β1、IL-6水平均显著升高（P＜0.01）；肺泡中出现大量炎症浸染及细胞纤维化等病变，且有大量胶原蛋白沉积，HE染色和Masson染色评分均显著升高（P＜0.01）；肺组织中α-SMA、CollagenⅠ、p-ERK1/2及TGF-β1蛋白表达均显著上调（P＜0.01）。与模型组比较，蒙花苷高剂量组小鼠上述指标均显著改善（P＜0.05或P＜0.01），蒙花苷低剂量组大部分指标（除肺指数外）均显著改善（P＜0.05或P＜0.01）。在体外实验中，与空白组比较，模型组细胞出现密度变大、明显增殖等变化，细胞中α-SMA、CollagenⅠ和p-ERK1/2蛋白表达均显著上调（P＜0.05或P＜0.01）。与模型组比较，蒙花苷各浓度组细胞密度变小，形态逐渐恢复正常；蒙花苷高浓度组细胞中上述蛋白及蒙花苷中浓度组细胞中p-ERK1/2蛋白表达均显著下调（P＜0.05或P＜0.01）。结论蒙花苷可能通过调控ERK及炎症相关通路，减轻炎症反应，从而发挥抗肺纤维化作用。 |
| ABSTRACT： | OBJECTIVE To investigate the anti-pulmonary fibrosis effect of linarin in vivo and in vitro， and investigate its mechanism preliminarily. METHODS C57BL/6J mice were randomly divided into normal group （carboxymethylcellulose sodium）， model group （carboxymethylcellulose sodium）， positive control group （pirfenidone， 200 mg/kg）， linarin low-dose and high-dose groups （12.5， 25 mg/kg）， with 8 mice in each group. Except for normal group， pulmonary fibrosis model was induced in other groups. After modeling， they were given relevant medicine intragastrically， once a day， for consecutive 14 d. The general situation of mice was observed， and their lung indexes were measured； the levels of tumor necrosis factor-α （TNF-α） and transforming growth factor-β1（ TGF-β1） in serum and interleukin-6 （IL-6） in lung tissue were determined. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the histopathological morphology of lung. The pulmonary fibrosis was scored according to Ashcroft score standard. The expressions of α-smooth muscle actin （α-SMA） and （type Ⅰ collagen， Collagen Ⅰ）， phosphorylated extracellular signal-regulated kinase （p-ERK1/2） and TGF-β1 in lung tissues were detected. HFL1 cells were stimulated by TGF- β1 to form pulmonary fibrosis model in vitro， which were divided into normal group， model group and linarin low-， medium- and high-concentration groups （3.7， 7.4， 14.8 mg/L）. After being cultured for 48 h， the protein expressions of α-SMA， Collagen Ⅰ and p-ERK1/2 in HFL1 cells were detected. RESULTS In vivo， compared with normal group， the lung index of model group and the levels of TNF- α， TGF- β1 and IL-6 were significantly increased （P＜0.01）. There were a large number of inflammatory infiltration and cellular fibrosis lesions in the alveoli， and a large number of collagen depositions. The scores of HE staining and Masson staining were significantly increased （P＜0.01）. The protein expressions of α-SMA， Collagen Ⅰ， p-ERK1/2 and TGF-β1 in lung tissue were up-regulated significantly （P＜0.01）. Compared with model group， above indexes of mice were improved significantly in linarin high-dose group （P＜0.05 or P＜0.01）， and most of indexes （except for lung index） were improved significantly in linarin low-dose group （P＜0.05 or P＜0.01）. In vitro， compared with blank group， the density of cells in the model group increased， and obvious proliferation and other changes occurred； protein expressions of α-SMA， Collagen Ⅰ and p-ERK1/2 were significantly up-regulated （P＜0.05 or P＜0.01）. Compared with model group， the cell density of each concentration group was decreased and the morphology gradually returned to normal； the expressions of above proteins in linarin high-concentration group and the protein expression of p-ERK1/2 in linarin medium-concentration group were down-regulated significantly（P＜0.05 or P＜0.01）. CONCLUSIONS Linarin may regulate ERK and inflammatory pathways to reduce the inflammatory response， thereby exerting anti-pulmonary fibrosis effect. |
| 期刊： | 2023年第34卷第03期 |
| 作者： | 黄梨婷；王珠强；王依婷；范卫锋；董更婷；彭伟文 |
| AUTHORS： | HUANG Liting，WANG Zhuqiang，WANG Yiting，FAN Weifeng，DONG Gengting，PENG Weiwen |
| 关键字： | 蒙花苷；肺纤维化；胞外信号调节激酶通路；炎症通路 |
| KEYWORDS： | linarin； pulmonary fibrosis； extracellular signal-regulated kinase pathway； inflammatory pathway |
| 阅读数： | 166 次 |
| 本月下载数： | 4 次 |
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