Effect of <italic style="font-style: italic">Wenfei Huaxian Granule </italic>（温肺化纤颗粒） on Lung Injury in Mice with Pulmonary Fibrosis based on Endoplasmic Reticulum Stress Signaling Pathway

Guoshuang ZHU; Mingliang QIU; Shiwen KE; Shaofeng LI; Lisha MO; Lei XU; Liangji LIU

doi:10.13288/j.11-2166/r.2021.22.012

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Effect of Wenfei Huaxian Granule （温肺化纤颗粒） on Lung Injury in Mice with Pulmonary Fibrosis based on Endoplasmic Reticulum Stress Signaling Pathway

更新时间：2021-11-29

- Effect of Wenfei Huaxian Granule （温肺化纤颗粒） on Lung Injury in Mice with Pulmonary Fibrosis based on Endoplasmic Reticulum Stress Signaling Pathway
- Journal of Traditional Chinese Medicine Vol. 62, Issue 22, Pages: 1988-1995(2021)
- 作者机构：
  
  1.江西中医药大学中医学院，江西省南昌市湾里区梅岭大道1688号，330004
  2.江西中医药大学附属医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2021.22.012
  CLC：
- Received：28 June 2021，
  
  Revised：2021-09-10，
  
  Published：17 November 2021
- 稿件说明：
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朱国双,邱明亮,柯诗文等.基于内质网应激信号通路探讨温肺化纤颗粒对肺纤维化模型小鼠肺损伤的影响[J].中医杂志,2021,62(22):1988-1995.

ZHU Guoshuang,QIU Mingliang,KE Shiwen,et al.Effect of Wenfei Huaxian Granule （温肺化纤颗粒） on Lung Injury in Mice with Pulmonary Fibrosis based on Endoplasmic Reticulum Stress Signaling Pathway[J].Journal of Traditional Chinese Medicine,2021,62(22):1988-1995.
朱国双,邱明亮,柯诗文等.基于内质网应激信号通路探讨温肺化纤颗粒对肺纤维化模型小鼠肺损伤的影响[J].中医杂志,2021,62(22):1988-1995. DOI： 10.13288/j.11-2166/r.2021.22.012.

ZHU Guoshuang,QIU Mingliang,KE Shiwen,et al.Effect of Wenfei Huaxian Granule （温肺化纤颗粒） on Lung Injury in Mice with Pulmonary Fibrosis based on Endoplasmic Reticulum Stress Signaling Pathway[J].Journal of Traditional Chinese Medicine,2021,62(22):1988-1995. DOI： 10.13288/j.11-2166/r.2021.22.012.

摘要

目的

探讨温肺化纤颗粒治疗肺纤维化的可能作用机制。

方法

将50只昆明小鼠随机分为空白对照组、模型组及温肺化纤颗粒低、中、高剂量组，每组10只。除空白对照组外，其余各组小鼠通过气管内滴注博来霉素构建肺纤维化模型。造模后，温肺化纤颗粒低、中、高剂量组小鼠分别给予温肺化纤颗粒混悬液2.925、5.85和11.7 g/（kg·d）灌胃，空白对照组和模型组给予生理盐水0.1 ml/10 g灌胃，连续28天。末次灌胃24h后采用HE和Masson染色观察小鼠肺组织病理损伤；Real-time PCR检测小鼠肺组织克老素（Klotho）、转化生长因子β1（TGF-β1）、α平滑肌肌动蛋白（α-SMA）、葡萄糖调节蛋白78（GRP78）、C/EBP 同源蛋白（CHOP） mRNA表达；Western blot法检测小鼠肺组织Klotho、GRP78、CHOP、B淋巴细胞瘤2相关X（Bax）、B淋巴细胞瘤2（Bcl-2）蛋白表达；免疫组化法观察肺组织TGF-β1、α-SMA蛋白表达。

结果

与空白对照组比较，模型组小鼠肺脏病理切片显示肺泡间隔增厚、病变区肺泡结构受到破坏，可见明显的蓝色胶原纤维沉积。肺组织中TGF-β1、α-SMA、GRP78、CHOP mRNA表达明显升高，Klotho mRNA表达明显降低（

＜0.01），TGF-β1、α-SMA、GRP78、CHOP、Bax蛋白表达明显增加，Klotho、Bcl-2蛋白表达明显减少（

＜0.01）。与模型组比较，温肺化纤颗粒各剂量组小鼠肺脏损伤减轻、肺泡间隔稍增厚、病变肺泡结构破坏减轻，小鼠肺脏中蓝色胶原纤维沉积减少，肺组织中TGF-β1、α-SMA、GRP78、CHOP mRNA表达明显降低，Klotho mRNA表达明显升高（

＜0.01），温肺化纤颗粒中、高剂量组GRP78、CHOP、Bax蛋白表达明显降低，温肺化纤颗粒各剂量组Klotho、Bcl-2蛋白表达明显升高（

＜0.01）；与温肺化纤颗粒低、高剂量组比较，温肺化纤颗粒中剂量组蓝色胶原纤维沉积最少，α-SMA、GRP78、CHOP mRNA降低，Klotho mRNA表达升高，Bax、GRP78、CHOP蛋白表达降低，Bcl-2蛋白表达升高（

＜0.05或

＜0.01）。

结论

温肺化纤颗粒具有抑制肺纤维化的作用，其机制可能是通过抑制内质网应激介导的凋亡发生，从而减少上皮间质转化。

Abstract

Objective

To investigate the possible mechanism of

Wenfei Huaxian Granule

（温肺化纤颗粒， WHG） in treating pulmonary fibrosis （PF）.

Methods

Fifty Kunming mice were randomly divided into blank control group， model group， WHG low， medium and high dose groups， with 10 mice in each group. Except for the blank control group， bleomycin were instilled into the trachea of the mice to develop PF models. After modelling， the suspension of WHG at the dose of 2.925 g/（kg·d）， 5.85 g/（kg·d） and 11.7 g/（kg·d） were given by gavage to the mice in WHG low， medium and high dose groups， respectively， while the blank control group and the model group were given 0.1mL/10g of normal saline by gavage； the administration in all the groups lasted for 28 days. HE and Masson staining were used to detect the pathological changes of lung in mice 24h after the last administration； real-time PCR was used to detect the Klotho， transforming growth factor β1 （TGF-β1）， α-smooth muscle actin （α-SMA）， glucose regulatory protein 78 （GRP78） and C/EBP homologous protein （CHOP） mRNA expression； the expressions of Klotho， GRP78， CHOP， B lymphoma 2 related X （Bax） and B lymphoma 2 （Bcl-2） protein were detected by Western blotting； TGF-β1 and α-SMA protein expression in the lung tissues were detected by immunohistochemistry.

Results

Compared to those in the blank group， the alveolar septum in the model group was thickened； the alveolar structure in the lesion area was damaged， and obvious deposition of blue collagen fibers was observed. The expression of TGF-β1， α-SMA， GRP78 and CHOP mRNA increased significantly （

＜0.01）， while Klotho mRNA decreased significantly （

＜0.01）； the expression of TGF-β1， α-SMA， GRP78， CHOP and Bax protein increased significantly （

＜0.01）， while the expression of Klotho and Bcl-2 protein decreased significantly （

＜0.01）. Compared to those in the model group， the lung injury， alveolar septum thickening， alveolar structure damage and deposition of blue collagen fibers in the lung of mice in WHG low， medium and high dose groups were improved； the expression of TGF-β1， α-SMA， GRP78 and CHOP mRNA decreased significantly （

＜0.01）， while Klotho mRNA expression increased significantly （

＜0.01）； the expression of GRP78， CHOP and Bax proteins in the WHG medium and high dose groups decreased significantly （

＜0.01）， and the expression of Klotho and Bcl-2 proteins in all the dose groups of WHG increased significantly （

＜0.01）. When compared between different doses of WHG， the medium dose group had the least blue collagen fiber deposition， the lowest expression of α-SMA， GRP78， and CHOP mRNA， the highest expression of Klotho mRNA，the lowest expression of Bax， GRP78 and CHOP proteins， and the highest expression of Bcl-2 protein （

＜0.05 or

＜0.01）.

Conclusion

WHG can inhibit the PF， and its mechanism maybe related to the inhibition of endoplasmic reticulum stress-induced apoptosis， thereby reducing epithelial-mesenchymal transition.

关键词

Keywords

references

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Effect of Wenfei Huaxian Granule （温肺化纤颗粒） on Lung Injury in Mice with Pulmonary Fibrosis based on Endoplasmic Reticulum Stress Signaling Pathway

DOI：10.13288/j.11-2166/r.2021.22.012

摘要

Abstract

关键词

Keywords

references