Protective effect of hyperoside on paraquat-induced acute lung injury in rats

WU Zhuo; CHEN Yue; WANG Qin-yu; GU Chun-yu; CHEN Xin-jun

doi:10.11659/jjssx.02E023025

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Protective effect of hyperoside on paraquat-induced acute lung injury in rats

Basic Research | 更新时间：2024-02-02

- Protective effect of hyperoside on paraquat-induced acute lung injury in rats
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 33, Issue 2, Pages: 112-117(2024)
- 作者机构：
  
  1.陕西省人民医院医学装备部，陕西西安 710068
  2.陕西省人民医院急诊内科，陕西西安 710068
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.02E023025
  CLC： R563.9
- Published：25 February 2024，
  
  Received：06 February 2023，
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武卓,陈乐,王卿语等.金丝桃甙对百草枯诱导的大鼠急性肺损伤的保护作用[J].局解手术学杂志,2024,33(02):112-117.

WU Zhuo,CHEN Yue,WANG Qin-yu,et al.Protective effect of hyperoside on paraquat-induced acute lung injury in rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(02):112-117.
武卓,陈乐,王卿语等.金丝桃甙对百草枯诱导的大鼠急性肺损伤的保护作用[J].局解手术学杂志,2024,33(02):112-117. DOI： 10.11659/jjssx.02E023025.

WU Zhuo,CHEN Yue,WANG Qin-yu,et al.Protective effect of hyperoside on paraquat-induced acute lung injury in rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(02):112-117. DOI： 10.11659/jjssx.02E023025.

摘要

目的

探究金丝桃甙（HYP）对百草枯（PQ）诱导的大鼠急性肺损伤的保护作用及其机制。

方法

将大鼠随机分为对照组、PQ组、低剂量金丝桃甙组（HYP-L组）、中剂量金丝桃甙组（HYP-M组）和高剂量金丝桃甙组（HYP-H组），每组12只。给予相应处理7 d后，检测各组大鼠支气管肺泡灌洗液（BALF）中的白细胞介素（IL）-1β、IL-6和巨噬细胞炎性蛋白-2（MIP-2）水平，以及肺组织中的丙二醛（MDA）和超氧化物歧化酶（SOD）水平。通过苏木精-伊红（HE）染色和Masson三色染色评估大鼠肺损伤和纤维化程度。通过Western blot检测肺组织中E-cadherin、α平滑肌肌动蛋白（α-SMA）、Vimentin及核因子红细胞2相关因子2（Nrf2）、核因子-κB（NF-κB） p65、p-NF-κB p65、转化生长因子-β1（TGF-β1）、Smad3和p-Smad3蛋白的表达水平。

结果

与对照组比较，PQ组大鼠BALF中的IL-1β、IL-6和MIP-2水平升高（

0.05），肺组织中SOD水平降低（

0.05），而MDA水平升高（

0.05），肺组织出现明显损伤和纤维化（

0.05）。与PQ组比较，HYP-L组、HYP-M组和HYP-H组大鼠BALF中的IL-1β、IL-6和MIP-2水平降低（

0.05），肺组织中SOD水平升高（

0.05），而MDA水平降低（

0.05），肺组织损伤减轻，纤维化评分降低（

0.05）。与对照组比较，PQ组大鼠肺组织中E-cadherin的表达水平降低（

0.05），α-SMA和Vimentin的表达水平升高（

0.05），Nrf2的蛋白表达水平降低（

0.05），TGF-β1的蛋白表达水平以及NF-κB p65和Smad3蛋白的磷酸化水平均升高（

0.05）。与PQ组比较，HYP-L组、HYP-M组和HYP-H组大鼠肺组织中E-cadherin的表达水平升高（

0.05），α-SMA和Vimentin的表达水平降低（

0.05），Nrf2的蛋白表达水平升高（

0.05），TGF-β1的蛋白表达水平以及NF-κB p65和Smad3蛋白的磷酸化水平降低（

0.05）。

结论

金丝桃甙有效减轻了百草枯诱导的大鼠急性肺损伤，其可能通过调节Nrf2、NF-κB和TGF-β1/Smad2/3信号通路减轻肺部氧化应激、炎症和纤维化。

Abstract

Objective

To investigate the protective effect and mechanism of hyperoside （HYP） on paraquat （PQ）-induced acute lung injury in rats.

Methods

Rats were randomly divided into the control group，the PQ group，the low-dose hyperoside group （HYP-L group），the middle-dose hyperoside group （HYP-M group） and the high-dose hyperoside group （HYP-H group），with 12 rats in each group. After 7 days of corresponding treatment，the levels of interleukin （IL）-1β，IL-6 and macrophage inflammatory protein-2 （MIP-2） in bronchoalveolar lavage fluid （BALF） of rats in each group，as well as the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） in lung tissue were detected. The degree of lung injury and fibrosis of rats were evaluated by hematoxylin-eosin （HE） staining and Masson's

trichrome staining. The expression levels of E-cadherin，α-smooth muscle actin （α-SMA），Vimentin，and protein expression levels of nuclear factor erythroid 2-related factor 2 （Nrf2），nuclear factor-κB （NF-κB） p65，p-NF-κB p65，transforming growth factor-β1 （TGF-β1），Smad3 and p-Smad3 in lung tissue were detected by Western blot.

Results

Compared with the control group，the levels of IL-1β，IL-6 and MIP-2 in BALF of rats in the PQ group increased （

0.05），the level of SOD in the lung tissue decreased，while the level of MDA increased （

0.05），and the lung tissue showed obvious damage and fibrosis （

0.05）. Compared with the PQ group，the levels of IL-1β，IL-6 and MIP-2 in BALF of rats in the HYP-L group，the HYP-M group and the HYP-H group decreased （

0.05），the levels of SOD in the lung tissue increased（

0.05），while the levels of MDA decreased （

0.05），and the lung tissue damages were alleviated，and the fibrosis score decreased （

0.05）. Compared with the control group，the expression level of E-cadherin in the lung tissue of rats in the PQ group decreased （

0.05），the expression levels of α-SMA and Vimentin increased （

0.05），the protein expression level of Nrf2 decreased （

0.05），the protein expression level of TGF-β1 and the phosphorylation levels of NF-κB p65 and Smad3 proteins increased （

0.05）. Compared with the PQ group，the expression levels of E-cadherin in the lung tissues of rats in the HYP-L group，the HYP-M group and the HYP-H group increased （

0.05），the expression levels of α-SMA and Vimentin decreased （

0.05），the protein expression levels of Nrf2 increased （

0.05），the protein expression level of TGF-β1 and the phosphorylation levels of NF-κB p65 and Smad3 proteins decreased （

0.05）.

Conclusion

Hyperoside effectively alleviates paraquat-induced acute lung injury in rats，and it may reduce lung oxidative stress，inflammation and fibrosis by regulating Nrf2，NF-κB and TGF-β1/Smad2/3 signal pathways.

关键词

百草枯金丝桃甙肺损伤氧化应激炎症纤维化

Keywords

paraquathyperosidelung injuryoxidative stressinflammationfibrosis

references

Sun Z，Yang Z，Wang M，et al.Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation［J］.Toxicol Lett，2020，333：170-183.doi：10.1016/j.toxlet. 2020.08.004http://dx.doi.org/10.1016/j.toxlet.2020.08.004.

Dinis-Oliveira RJ，Duarte JA，Sánchez-Navarro A，et al.Paraquat poisonings：mechanisms of lung toxicity，clinical features，and treatment［J］.Crit Rev Toxicol，2008，38（1）：13-71.doi：10.1080/1040844 0701669959http://dx.doi.org/10.1080/10408440701669959.

Liu X，Yang H，Liu Z.Signaling pathways involved in paraquat-induced pulmonary toxicity：molecular mechanisms and potential therapeutic drugs［J］.Int Immunopharmacol，2022，113（Pt A）：109301.doi：10.1016/j.intimp.2022.109301http://dx.doi.org/10.1016/j.intimp.2022.109301.

Tai W，Deng S，Wu W，et al.Rapamycin attenuates the paraquat-induced pulmonary fibrosisthrough activating Nrf2 pathway［J］.J Cell Physiol，2020，235（2）：1759-1768.doi：10.1002/jcp.29094http://dx.doi.org/10.1002/jcp.29094.

Jin H.Imrecoxib inhibits paraquat-induced pulmonary fibrosis through the NF-κB/Snail signaling pathway［J］.Comput Math Methods Med，2020，2020：6374014.doi：10.1155/2020/6374014http://dx.doi.org/10.1155/2020/6374014.

Bai YW，Ye MJ，Yang DL，et al.Hydrogen sulfide attenuates paraquat-induced epithelial-mesenchymal transition of human alveolar epithelial cells through regulating transforming growth factor-β1/Smad2/3 signaling pathway［J］.J Appl Toxicol，2019，39（3）：432-440.doi：10.1002/jat.3734http://dx.doi.org/10.1002/jat.3734.

Wang Q，Wei HC，Zhou SJ，et al.Hyperoside：A review on its sources，biological activities，and molecular mechanisms［J］.Phytother Res，2022，36（7）：2779-2802.doi：10.1002/ptr.7478http://dx.doi.org/10.1002/ptr.7478.

Wang X，Liu Y，Xiao L，et al.Hyperoside protects against pressure overload-induced cardiac remodeling via the AKT signaling pathway［J］.Cell Physiol Biochem，2018，51（2）：827-841.doi：10.1159/000495368http://dx.doi.org/10.1159/000495368.

Guo X，Zhu C，Liu X，et al.Hyperoside protects against heart failure-induced liver fibrosis in rats［J］.Acta Histochem，2019，121（7）：804-811.doi：10.1016/j.acthis.2019.07.005http://dx.doi.org/10.1016/j.acthis.2019.07.005.

Yan Y，Feng Y，Li W，et al.Protective effects of quercetin and hyperoside on renal fibrosis in rats with unilateral ureteral obstruction［J］.Exp Ther Med，2014，8（3）：727-730.doi：10.3892/etm.2014.1841http://dx.doi.org/10.3892/etm.2014.1841.

Huang J，Tong X，Zhang L，et al.Hyperoside attenuates bleomycin-induced pulmonary fibrosis development in mice［J］.Front Pharmacol，2020，11：550955.doi：10.3389/fphar.2020.550955http://dx.doi.org/10.3389/fphar.2020.550955.

Zou L，Chen S，Li L，et al.The protective effect of hyperoside on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2［J］.Exp Toxicol Pathol，2017，69（7）：451-460.doi：10.1016/j.etp.2017.04.001http://dx.doi.org/10.1016/j.etp.2017.04.001.

Ashcroft T，Simpson JM，Timbrell V.Simple method of estimating severity of pulmonary fibrosis on a numerical scale［J］.J Clin Pathol，1988，41（4）：467-470.doi：10.1136/jcp.41.4.467http://dx.doi.org/10.1136/jcp.41.4.467.

Podder B，Kim YS，Zerin T，et al.Antioxidant effect of silymarin on paraquat-induced human lung adenocarcinoma A549 cell line［J］.Food Chem Toxicol，2012，50（9）：3206-3214.doi：10.1016/j.fct.2012.06.007http://dx.doi.org/10.1016/j.fct.2012.06.007.

Zhu Y，Meng X，Yang W，et al.HIF-1α promotes paraquat induced acute lung injury and implicates a role NF-κB and Rac2 activity［J］.Toxicology，2023，483：153388.doi：10.1016/j.tox.2022.153388http://dx.doi.org/10.1016/j.tox.2022.153388.

Klueh U，Antar O，Qiao Y，et al.Role of interleukin-1/interleukin-1 receptor antagonist family of cytokines in long-term continuous glucose monitoring in vivo［J］.J Diabetes Sci Technol，2013，7（6）：1538-1546.doi：10.1177/193229681300700614http://dx.doi.org/10.1177/193229681300700614.

Miao JW，Liu LJ，Huang J.Interleukin-6-induced epithelial-mesenchymal transition through signal transducer and activator of transcription 3 in human cervical carcinoma［J］.Int J Oncol，2014，45（1）：165-176.doi：10.3892/ijo.2014.2422http://dx.doi.org/10.3892/ijo.2014.2422.

Fu PK，Yang CY，Tsai TH，et al.Moutan cortex radicis improves lipopolysaccharide-induced acute lung injury in rats through anti-inflammation［J］.Phytomedicine，2012，19（13）：1206-1215.doi：10.1016/j.phymed.2012.07.013http://dx.doi.org/10.1016/j.phymed.2012.07.013.

Han YY，Shen P，Chang WX.Involvement of epithelial-to-mesenchymal transition and associated transforming growth factor-β/Smad signaling in paraquat-induced pulmonary fibrosis［J］.Mol Med Rep，2015，12（6）：7979-7984.doi：10.3892/mmr.2015.4454http://dx.doi.org/10.3892/mmr.2015.4454.

Kim YS，Podder B，Song HY.Cytoprotective effect of alpha-lipoic acid on paraquat-exposed human bronchial epithelial cells via activation of nuclear factor erythroid related factor-2 pathway［J］.Biol Pharm Bull，2013，36（5）：802-811.doi：10.1248/bpb.b12-00977http://dx.doi.org/10.1248/bpb.b12-00977.

Jiang Z，Wang J，Liu C，et al.Hyperoside alleviated N-acetyl-para-amino-phenol-induced acute hepatic injury via Nrf2 activation［J］.Int J Clin Exp Pathol，2019，12（1）：64-76.

Kwon SH，Lee SR，Park YJ，et al.Suppression of 6-hydroxydopamine-induced oxidative stress by hyperoside via activation of Nrf2/HO-1 signaling in dopaminergic neurons［J］.Int J Mol Sci，2019，20（23）：5832.doi：10.3390/ijms20235832http://dx.doi.org/10.3390/ijms20235832.

Xie T，Yuan J，Mei L，et al.Hyperoside ameliorates TNF‑α‑induced inflammation，ECM degradation and ER stress‑mediated apoptosis via the SIRT1/NF‑κB and Nrf2/ARE signaling pathways in vitro［J］.Mol Med Rep，2022，26（2）：260.doi：10.3892/mmr.2022.12776http://dx.doi.org/10.3892/mmr.2022.12776.

Chen T，Wang R，Jiang W，et al.Protective effect of astragaloside IV against paraquat-induced lung injury in mice by suppressing rho signaling［J］.Inflammation，2016，39（1）：483-492.doi：10.1007/s10753-015-0272-4http://dx.doi.org/10.1007/s10753-015-0272-4.

Chen X，Famurewa AC，Tang J，et al.Hyperoside attenuates neuroinflammation，cognitive impairment and oxidative stress via suppressing TNF-α/NF-κB/caspase-3 signaling in type 2 diabetes rats［J］.Nutr Neurosci，2022，25（8）：1774-1784.doi：10.1080/1028415X.2021.1901047http://dx.doi.org/10.1080/1028415X.2021.1901047.

Xu T，Wu X，Zhou Z，et al.Hyperoside ameliorates periodontitis in rats by promoting osteogenic differentiation of BMSCs via activation of the NF-κB pathway［J］.FEBS Open Bio，2020，10（9）：1843-1855.doi：10.1002/2211-5463.12937http://dx.doi.org/10.1002/2211-5463.12937.

Lovisa S，LeBleu VS，Tampe B，et al.Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis［J］.Nat Med，2015，21（9）：998-1009.doi：10.1038/nm.3902http://dx.doi.org/10.1038/nm.3902.

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