Youguiwan Reduces Airway Inflammation in COPD Rats with Syndrome of Kidney-Yang Deficiency by Inhibiting Leptin/JAK2/STAT3 Signaling Pathway
10.13422/j.cnki.syfjx.20240522
- VernacularTitle:右归丸调节Leptin/JAK2/STAT3信号通路抑制肾阳虚COPD大鼠气道炎症
- Author:
Lan ZHENG
1
;
Zeyuan LUO
2
;
Min XIAO
3
;
Xiaocui JIANG
3
;
Yuhao MENG
4
;
Siyi CHEN
2
;
Jing ZHOU
1
Author Information
1. First Clinical College， Hubei University of Chinese Medicine， Wuhan 430061， China
2. College of Traditional Chinese Medicine， Hubei University of Chinese Medicine， Wuhan 430061， China
3. Hubei Shizhen Laboratory， Wuhan 430061， China
4. College of Basic Medical Sciences， Hubei University of Chinese Medicine， Wuhan 430065， China
- Publication Type:Journal Article
- Keywords:
chronic obstructive pulmonary disease （COPD）;
Youguiwan;
interleukin-17A （IL-17A）;
leptin;
Janus kinase 2/signal transducer and activator of transcription 3
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(14):17-26
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of Youguiwan on the leptin/Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） due to kidney-Yang deficiency. MethodForty rats were modeled for COPD with the syndrome of kidney-Yang deficiency by intratracheal instillation of lipopolysaccharide on day 1 and day 14 and continuous fumigation for 6 weeks， during which hydrocortisone was injected intramuscularly at an interval of 3 days. The modeled rats were randomized into model， high- （11.7 g·kg-1）， medium- （5.85 g·kg-1）， and low-dose （2.93 g·kg-1） Youguiwan， and aminophylline （0.054 g·kg-1） group. In addition， 8 SD rats were set as the blank group. After the completion of modeling， the rats in each group were administrated with the corresponding drug by gavage for 28 consecutive days. After the last administration， samples were collected. A lung function analyzer was used to evaluate the lung function of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-17A （IL-17A）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF）. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung tissue， and Masson staining was employed to observe the deposition of blue collagen fibers around bronchi in the lung tissue and calculate the inflammation score. The immunofluorescence assay was employed to measure the protein content of collagen type Ⅰ （ColⅠ） and α-smooth muscle actin （α-SMA） in the bronchi. The protein and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed decreased lung function （P<0.01）， elevated levels of IL-6， IL-17A， and TNF-α in the BALF （P<0.01）， and increased lung inflammation score， deposition of subcutaneous collagen fibers in the airway， and ColⅠ and α-SMA proteins （P<0.01）. Furthermore， the modeling up-regulated the proteins and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue （P<0.01） and enhanced the phosphorylation of JAK2 and STAT3 （P<0.01）. Compared with the model group， high- and medium-dose Youguiwan improved the lung function， decreased the inflammation score， reduced collagen fiber deposition and ColⅠ and α-SMA proteins， lowered the levels of IL-6， IL-17A， and TNF-α in the BALF， down-regulated the mRNA and protein levels of leptin， JAK2， STAT3， and IL-17A， and weakened the phosphorylation of JAK2 and STAT3 （P<0.05， P<0.01）. The aminophylline group had higher IL-17A and TNF-α levels than the high-dose Youguiwan group， lower IL-17A level than the medium and low-dose Youguiwan groups， and lower TNF-α level than the low-dose Youguiwan group. Compared with the aminophylline group， the high- and medium-dose Youguiwan groups showed reduced deposition of collagen fibers and protein levels of ColⅠ and α-SMA around the bronchi in the lung tissue （P<0.05， P<0.01）， decreased inflammation score， and down-regulated protein and mRNA levels of leptin， JAK2， STAT3， and IL-17A in the lung tissue. ConclusionYouguiwan can prevent airway remodeling by inhibiting IL-17A to reduce inflammation and collagen deposition in COPD rats， which may be related to the inhibition of the leptin/JAK2/STAT3 signaling pathway.
