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Study on the anti-pulmonary fibrosis effect of linarin
in vivo andin vitro and its mechanism- ZHONGGUO YAOFANG Vol. 34, Issue 3, Pages: 333-338(2023)
- 作者机构：
广州中医药大学附属中山中医院药学部，广东 中山 528400
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2023.03.15
CLC： R965Published：15 February 2023，
Received：31 August 2022，
Revised：27 December 2022，
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黄梨婷,王珠强,王依婷等.蒙花苷体内外抗肺纤维化作用及其机制研究 Δ[J].中国药房,2023,34(03):333-338.
HUANG Liting,WANG Zhuqiang,WANG Yiting,et al.Study on the anti-pulmonary fibrosis effect of linarin in vivo and in vitro and its mechanism[J].ZHONGGUO YAOFANG,2023,34(03):333-338.
黄梨婷,王珠强,王依婷等.蒙花苷体内外抗肺纤维化作用及其机制研究 Δ[J].中国药房,2023,34(03):333-338. DOI： 10.6039/j.issn.1001-0408.2023.03.15.
HUANG Liting,WANG Zhuqiang,WANG Yiting,et al.Study on the anti-pulmonary fibrosis effect of linarin in vivo and in vitro and its mechanism[J].ZHONGGUO YAOFANG,2023,34(03):333-338. DOI： 10.6039/j.issn.1001-0408.2023.03.15.
摘要
目的
2
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
2
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，200 mg/kg）和蒙花苷低、高剂量组（12.5、25 mg/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14 d。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
1
（TGF-β
1
）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（Collagen Ⅰ）、磷酸化胞外信号调节激酶（p-ERK1/2）、TGF-β
1
的表达水平。使用TGF-β
1
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、14.8 mg/L），培养48 h后，检测细胞中
α
-SMA、Collagen Ⅰ、p-ERK1/2蛋白表达水平。
结果
2
在体内实验中，与正常组比较，模型组小鼠肺指数和TNF-α、TGF-β
1
、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、Collagen
Ⅰ、p-ERK1/2及TGF-β
1
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、Collagen Ⅰ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
2
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
2
To investigate the anti-pulmonary fibrosis effect of linarin
in vivo
and
in vitro
， and investigate its mechanism preliminarily.
METHODS
2
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-β
1
（TGF-β
1
） 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-β
1
in lung tissues were detected. HFL1 cells were stimulated by TGF-β
1
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
2
In vivo
， compared with normal group， the lung index of model group and the levels of TNF-α， TGF-β
1
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-β
1
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
2
Linarin may regulate ERK and inflammatory pathways to reduce the inflammatory response， thereby exerting anti-pulmonary fibrosis effect.
关键词
蒙花苷肺纤维化胞外信号调节激酶通路炎症通路
Keywords
pulmonary fibrosisextracellular signal-regulated kinase pathwayinflammatory pathway
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