Effect of <italic style="font-style: italic">Bufei Yishen Formula</italic> （补肺益肾方） on the Efferocytosis of Alveolar Macrophages and PPAR γ Pathway in Chronic Obstructive Pulmonary Disease Model Mice

Yingshuo WU; Yiwan SHANG; Danhua MENG; Zhexu ZHOU; Xing CHEN; Yaosong WU; Shanshan REN; Yan LIU; Yulong CHEN

doi:10.13288/j.11-2166/r.2021.23.012

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Effect of Bufei Yishen Formula （补肺益肾方） on the Efferocytosis of Alveolar Macrophages and PPAR γ Pathway in Chronic Obstructive Pulmonary Disease Model Mice

更新时间：2021-11-29

- Effect of Bufei Yishen Formula （补肺益肾方） on the Efferocytosis of Alveolar Macrophages and PPAR γ Pathway in Chronic Obstructive Pulmonary Disease Model Mice
- Journal of Traditional Chinese Medicine Vol. 62, Issue 23, Pages: 2084-2091(2021)
- 作者机构：
  
  河南中医药大学，河南省郑州市金水路126号，450000
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2021.23.012
  CLC：
- Received：11 June 2021，
  
  Revised：2021-08-29，
  
  Published：02 December 2021
- 稿件说明：
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武颖烁,尚艺婉,孟丹华等.补肺益肾方对慢性阻塞性肺疾病模型小鼠肺泡巨噬细胞胞葬功能及PPARγ通路的影响[J].中医杂志,2021,62(23):2084-2091.

WU Yingshuo,SHANG Yiwan,MENG Danhua,et al.Effect of Bufei Yishen Formula （补肺益肾方） on the Efferocytosis of Alveolar Macrophages and PPAR γ Pathway in Chronic Obstructive Pulmonary Disease Model Mice[J].Journal of Traditional Chinese Medicine,2021,62(23):2084-2091.
武颖烁,尚艺婉,孟丹华等.补肺益肾方对慢性阻塞性肺疾病模型小鼠肺泡巨噬细胞胞葬功能及PPARγ通路的影响[J].中医杂志,2021,62(23):2084-2091. DOI： 10.13288/j.11-2166/r.2021.23.012.

WU Yingshuo,SHANG Yiwan,MENG Danhua,et al.Effect of Bufei Yishen Formula （补肺益肾方） on the Efferocytosis of Alveolar Macrophages and PPAR γ Pathway in Chronic Obstructive Pulmonary Disease Model Mice[J].Journal of Traditional Chinese Medicine,2021,62(23):2084-2091. DOI： 10.13288/j.11-2166/r.2021.23.012.

摘要

目的

探究补肺益肾方治疗慢性阻塞性肺疾病（COPD）的可能作用机制。

方法

60只C57BL/6小鼠随机分为空白组、模型组、补肺益肾组、抑制剂组、抑制剂合补肺益肾组，每组12只。除空白组外其余各组小鼠采用香烟烟雾熏吸8周的方法制备小鼠COPD模型。造模后补肺益肾组给予补肺益肾方溶液5.31 g/（kg·d）灌胃，腹腔注射生理盐水（雄鼠0.20 ml/次，雌鼠0.15 ml/次）；抑制剂组给予过氧化物酶增殖物激活受体γ（PPARγ）通路抑制剂GW9662 1 mg/（kg·d）腹腔注射，灌胃生理盐水（雄鼠0.25 ml/次，雌鼠0.20 ml/次）；抑制剂合补肺益肾组给予补肺益肾方溶液灌胃和腹腔注射GW9662（剂量同上）；空白组与模型组小鼠采用生理盐水灌胃及腹腔注射（剂量同上）。各组均每日1次，每周6次。4周后检测小鼠体质量、肺功能指标［包括最终潮气量（TV）、每分钟呼气量（MV）、呼气峰流速（PEF）、50%潮气量呼气流量（EF50）］，肺组织匀浆中肿瘤坏死因子α（TNF-α）、白细胞介素（IL-4）含量，肺泡巨噬细胞胞葬能力、肺组织细胞凋亡指数及巨噬细胞CD163、诱导型一氧化氮合酶（iNOS）、PPARγ表达。HE染色观察肺组织病理变化。

结果

与空白组比较，模型组小鼠体质量、肺功能指标、肺泡巨噬细胞胞葬能力降低，肺组织匀浆中TNF-α、IL-4含量及肺组织凋亡指数上升，肺泡巨噬细胞CD163、iNOS表达上升，PPARγ表达降低，差异均有统计学意义（

＜0.01）。与模型组比较，补肺益肾组小鼠体质量、肺功能明显改善，肺组织匀浆中TNF-α、IL-4含量，巨噬细胞CD163、iNOS表达及肺组织细胞凋亡指数显著下降，肺泡巨噬细胞胞葬能力及PPARγ表达上升（

＜0.05或

＜0.01）；而抑制剂组、抑制剂合补肺益肾组小鼠体质量、肺功能指标、肺泡巨噬细胞胞葬能力、肺组织凋亡指数与CD163、PPARγ表达差异均无统计学意义（

＞0.05），肺组织匀浆中TNF-α、IL-4含量上升（

＜0.05或

＜0.01）。

结论

补肺益肾方可能通过调控COPD模型小鼠肺泡巨噬细胞胞葬功能及PPARγ通路起到治疗COPD的作用。

Abstract

Objective

To explore the possible mechanim of

Bufei Yishen Formula

（补肺益肾方， BYF） in the treatment of chronic obstructive pulmonary disease （COPD）.

Methods

Sixty C57BL/6 mice were randomly divided into blank group， model group， BYF group， inhibitor group， and combination （inhibitor combined with BYF） group， with 12 mice in each group. Except for the blank group， mice were immersed in cigarette smoke for 8 weeks to develop the COPD models. After modeling， the BYF group was given 5.31 g/（kg·d） BYF solution by gavage and normal saline （male 0.2 ml， female 0.15 ml each time） by intraperitoneal injection； inhibitor group was given 1 mg/（kg·d） GW9662， the inhibitor of peroxidase proliferator activated receptor gamma （PPARγ） pathway， by intraperitoneal injection and normal saline （male 0.25 ml， female 0.2 ml each time） by gavage； the combination group was given BYF solution （5.31 g/kg·d） by gavage and GW9662 （1 mg/kg·d） by intraperitoneal injection； the blank group and model group were given normal saline by gavage and by intraperitoneal injection with the same dosage as other groups； all administrations were given once daily， six times a week. After four weeks， the body weight of mice， the lung function indicators including final tidal volume （TV）， exhaled minute ventilation （MV）， peak expiratory flow （PEF）， and mid-tidal expiratory flow （EF50）， the content of tumor necrosis factor alpha （TNF-α） and interleukin-4 （IL-4） in lung tissue homogenate， the efferocytosis of alveolar macrophages， the lung tissue cells apoptotic index， and the expression of of macrophage CD163， inducible nitric oxide synthase （iNOS）， and PPARγ were assessed. HE staining was used to observe pathological changes of lung tissue.

Results

Compared to those in the blank group， the body weight of mice， the lung function indicators， and the efferocytosis of alveolar macrophages in the model group significantly decreased； the content of TNF-α and IL-4， the lung tissue cells apoptotic index， as well as the expression of CD163 and iNOS in alveolar macrophages increased significantly； and the expression of PPARγ significantly decreased （

＜0.01）. Compared to those in the model group， the body weight and the lung function indicators in the BYF group were significantly improved； the content of TNF-α and IL-4， the expression of CD163 and iNOS in pulmonary macrophages， and the lung tissue cells apoptotic index significantly decreased； and the efferocytosis of alveolar macrophages and the expression of PPARγ significantly increased （

＜0.05 or

＜0.01）. There were no significant differences in the body weight of mice， the lung function indicators， the efferocytosis of alveolar macrophages， the lung tissue cells apoptotic index， and the expression of CD163 and PPARγ between the model group and the inhibitor group and the combination group （

＞0.05）； but increased content of TNF-α and IL-4 were found in the inhibitor and the combination group （

＜0.05 or

＜0.01）.

Conclusion

BYF may act the role of treating COPD by regulating the efferocytosis of alveolar macrophages and the PPARγ pathway.

关键词

Keywords

references

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Effect of Bufei Yishen Formula （补肺益肾方） on the Efferocytosis of Alveolar Macrophages and PPAR γ Pathway in Chronic Obstructive Pulmonary Disease Model Mice

DOI：10.13288/j.11-2166/r.2021.23.012

摘要

Abstract

关键词

Keywords

references