Anti-inflammatory Mechanism of Modified Erchentang on Chronic Obstructive Pulmonary Disease Through Jagged1/Notch1/Hes1 Signaling Pathway
10.13422/j.cnki.syfjx.20230109
- VernacularTitle:二陈汤加味通过Jagged1/Notch1/Hes1信号通路对慢性阻塞性肺疾病的抗炎机制
- Author:
Lizhi SHANG
1
;
Shu JI
1
;
Yaoyang LI
1
;
Wenhao HU
2
;
Wenying XIE
1
;
Zhuang CHEN
1
;
Gaoyang LIU
1
;
Haofan SHANG
1
;
Hongwei WANG
1
Author Information
1. Henan University of Chinese Medicine,Zhengzhou 450046,China
2. Henan Second Provincial People's Hospital,Zhengzhou 451191,China
- Publication Type:Journal Article
- Keywords:
chronic obstructive pulmonary disease (COPD);
Erchentang;
Notch1 signaling pathway;
adhesion molecule
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(9):109-118
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of modified Erchentang on the expression of key molecules in the Jagged1/Notch1/Hes1 signaling pathway in lung tissues of rats with chronic obstructive pulmonary disease (COPD) and explore its anti-inflammatory effect and molecular mechanism on COPD through the Jagged1/Notch1/Hes1 signaling pathway. MethodSixty SD rats were randomly divided into normal group, model group, low-, medium-, and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), and γ-secretase inhibitor DAPT group (0.02 g·kg-1), with 10 rats in each group. The COPD model was induced in rats by cigarette smoking combined with intratracheal instillation of lipopolysaccharide (LPS). Rats were treated with corresponding drugs by gavage, while those in the normal group and the model group were treated with the same amount of normal saline by gavage. The serum levels of Notch1, soluble intercellular adhesion molecule-1 (sICAM-1), activated leukocyte cell adhesion molecule (ALCAM), and soluble vascular adhesion molecule-1 (sVCAM-1) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of Jagged1, Notch1, and Hes1 was detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The protein expression of Jagged1, Notch1, Notch1 intracellular domain (NICD1), and Hes1 in lung tissues of rats was detected by immunohistochemistry (IHC). ResultCompared with the normal group, the model group showed increased serum content of Notch1, sICAM-1, ALCAM, and sVCAM-1 (P<0.01), increased mRNA expression of Jagged1, Notch1, and Hes1 in lung tissues (P<0.01), and increased protein expression of Jagged1, Notch1, NICD1, and Hes1 (P<0.01). Compared with the model group, the medium- and high-dose modified Erchentang groups and the DAPT group showed decreased serum content of Notch1, sICAM-1, ALCAM, and sVCAM-1 (P<0.05, P<0.05), down-regulated mRNA expression of Jagged1, Notch1, and Hes1 (P<0.05, P<0.01), and reduced protein expression of Jagged1, Notch1, NICD1, and Hes1(P<0.05, P<0.01). ConclusionModified Erchentang may inhibit the inflammatory response in the lung of COPD rats, and its mechanism may be related to the resistance of inflammatory injury in the lung by decreasing the mRNA expression of Jagged1, Notch1, and Hes1 and inhibiting the release of Notch1, sICAM-1, ALCAM, and sVCAM-1.