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. 2022 Sep;38(5):559-563.
doi: 10.12047/j.cjap.6316.2022.104.

[Effects of Bu Zhong Yi Qi decoction on CIH-induced interstitial lung fibrosis in mice]

[Article in Chinese]
Yi Tang  1   2 , Bing-Bing Liu  1   2 , Qi Chen  1   2 , Ting-Ting Li  1   2 , En-Sheng Ji  1   2 , Jie-Ru Li  1   2
Affiliations
Free article

[Effects of Bu Zhong Yi Qi decoction on CIH-induced interstitial lung fibrosis in mice]

[Article in Chinese]
Yi Tang et al. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Sep.
Free article

Abstract
in English, Chinese

Objective: To investigate the effects of chronic intermittent hypoxia (CIH) on the expression of transforming growth factor-β (TGF-β), P-samd3, serum laminin (LN) and hyaluronidase (HA) in mouse lung tissues and the protective effects of Bu Zhong Yi Qi decoction on lung interstitial deposition damage in CIH mice.

Methods: Fifty SPF-grade C57BL mice were randomly divided into five groups (n=10): blank control group, CIH model group, and CIH+ low, medium and high doses of Bu Zhong Yi Qi decoction group. Mice were placed under normoxia or CIH conditions, respectively. The Chinese medicine group was given the corresponding doses of drugs. HE staining was performed to assess pathological changes and Masson staining was performed to assess collagen deposition. Western blot was performed to detect the expressions of channel proteins such as TGF-β1, P-smad3 and down stream α-SMA and Collagen I. ELISA was performed to detect the serum levels of TGF-β1, LN and HA.

Results: HE staining showed alveolar collapse, septal thickening and epithelial cell necrosis in CIH mice, Masson showed massive collagen fiber proliferation and deposition in lung interstitium, while the above changes in lung tissues were significantly improved in the CIH + Bu Zhong Yi Qi decoction groups compared with the CIH group. TGF-β1, P-smad3 and Collagen I, Collagen Ⅲ, and α-SMA expression levels were increased compared with the blank control group (P＜0.05), and the expressions of TGF-β1 and LN in serum were upregulated (P＜0.05). The expressions of TGF-β1, P-smad3, Collagen I protein and SMA-α in the lung tissues of the CIH+ Bu Zhong Yi Qi decoction groups were downregulated significantly compared with those of the CIH group (P＜0.05), and the improvement of multiple indexes in the CIH+high-dose CIH intervention group was better than those of the low-dose group (P＜0.05).

Conclusion: Bu Zhong Yi Qi decoction can inhibit alveolar structural changes and excessive collagen deposition in the interstitium of CIH mice, and then improve lung function in CIH mice. The mechanism may be related to the down-regulation of protein expression related to TGF-β/smads signaling pathway by Bu Zhong Yi Qi decoction.

目的: 观察慢性间歇性低氧(CIH)对小鼠肺组织转化生长因子-β(TGF-β)、P-samd3和血清层粘连蛋白(LN)、 透明质酸(HA)、表达的影响以及补中益气汤对CIH小鼠肺间质沉积损害的干预作用。方法: 随机将50只SPF级C57BL小鼠分为5组(n=10):空白对照组、 CIH模型组、CIH+低、中、高剂量补中益气汤组。分别置于常氧或CIH条件下,中药组给予对应剂量药物。在第35日无创肺功能检测后处死。HE染色评估病理学改变,Masson染色行胶原沉积评估;Western blot法检测TGF-β1、P-smad3等通道蛋白和下游α-SMA、Collagen I的蛋白表达水平;ELISA法检测血清中TGF-β1、LN、HA的质量浓度。结果: HE染色显示,CIH小鼠肺泡塌陷,肺间隔增厚,上皮细胞坏死;Masson显示,CIH小鼠肺间质大量胶原纤维增生、沉积,而补中益气汤干预组肺组织上述改变较CIH模型组明显减轻。CIH模型组肺组织中TGF-β1、P-smad3及Collagen I、Collagen Ⅲ、α-SMA蛋白表达水平与空白对照组相比明显上调(P＜0.05),血清中TGF-β1、LN的表达明显上调(P＜0.05)。补中益气汤干预组肺组织中TGF-β1、P-smad3、Collagen I蛋白及SMA-α的表达水平相较于CIH组有明显下调(P＜0.05)。结论: 补中益气汤可抑制CIH小鼠肺泡结构改变和肺间质的胶原过度沉积。其机制可能与补中益气汤下调TGF-β/smads信号通路的相关蛋白表达有关。.

Keywords: Bu Zhong Yi Qi decoction; P-smad3; TGF-β1; chronic intermittent hypoxia; mice; pulmonary fibrosis; type I collagen.

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