Mechanism of Modified Erchentang on COPD Inflammation Based on TNF-α/TNFR1/RIPKs Pathway / 中国实验方剂学杂志

ABSTRACT

ObjectiveBased on tumor necrosis factor alpha （TNF-α）/tumor necrosis factor receptor 1 （TNFR1）/receptor-interacting protein kinases （RIPKs） signaling pathway， this paper aims to study the effect of modified Erchentang on inflammation in rats with chronic obstructive pulmonary disease （COPD） and explore its mechanism of action. MethodA total of 60 SD rats were randomly divided into normal group， model group， high， medium， and low-dose groups （20， 10， 5 g·kg-1·d-1） of modified Erchentang， and Xiaokechuan group （3.5 mL·kg-1·d-1）， with 10 rats in each group. The COPD rat model was established by cigarette smoke combined with lipopolysaccharide （LPS）. The normal group and model group were given the same amount of normal saline for 21 days by gavage administration. The contents of TNF-α and TNFR1 in bronchoalveolar lavage fluid （BALF） of rats were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expressions of RIPK1， RIPK3， and mixed lineage kinase domain-like （MLKL） in the lung tissue. The protein expressions of RIPK1， RIPK3， and MLKL in the lung tissue were detected by Western blot. The pathological changes in lung tissue were observed by hematoxylin-eosin （HE） staining. ResultCompared with the normal group， the contents of TNF-α and TNFR1 in BALF of the model group were significantly increased （P<0.01）， and the mRNA and protein expression levels of RIPK1， RIPK3， and MLKL in the lung tissue were significantly increased （P<0.01）. Compared with the model group， the contents of TNF-α and TNFR1 in BALF of high， medium， and low-dose groups of modified Erchentang and Xiaokechuan group were decreased （P<0.01）. The mRNA and protein expression levels of RIPK1， RIPK3， and MLKL in the lung tissue were decreased to different degrees （P<0.05， P<0.01）. ConclusionModified Erchentang can effectively improve the inflammatory response of lung tissue in COPD rats， and the mechanism may be by inhibiting the activation of the TNF-α/TNFR1/RIPKs signaling pathway.