Pathogenesis of Airway Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Intervention of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD） is one of the most common chronic diseases of the respiratory system in the clinic. The disease has a long course and is difficult to cure， which seriously threatens human health. Airway mucus hypersecretion （AMH） is an independent risk factor for COPD and has a significant impact on the development and prognosis of the disease. The review finds that the abnormal proliferation of goblet cells and the excessive secretion of mucin are the direct causes of AMH. The pathogenesis of AMH may be closely related to the inhalation of heterogeneous particles， airway inflammation， the imbalance of mucin/water salt ratio， and the regulation of related signaling pathways. Traditional Chinese medicine （TCM） believes that AMH of COPD belongs to the category of lung distension with phlegm-fluid retention syndrome， and the disease is mainly treated from phlegm on the basis of lung distension. This article summarizes the relevant research in the field of TCM in recent years and finds that the single TCM that effectively intervened AMH of COPD is mainly phlegm-resolving TCM， and the main active ingredients of TCM are flavonoids， terpenoids， phenols， and alkaloids. The main TCM compounds are mainly designed to remove heat-phlegm， warmly resolve cold-phlegm， dry dampness to eliminate phlegm， invigorate Qi， promote blood circulation and dispel phlegm， and invigorate lung， spleen， and kidney. Its mechanism of action may be direct inhibition or indirect inhibition of airway epithelial goblet cell metaplasia and mucin expression by inhibiting airway inflammation， regulating aquaporins to correct the imbalance of mucin/water salt ratio， and regulating signaling pathways， so as to reduce mucus oversecretion in COPD. However， there are still some problems. For example， the research mainly focuses on TCM compounds instead of the single TCM or its effective components. The research on the mechanism of action is not thorough enough， and the research results are not interoperable. The clinical transformation rate of basic research is insufficient. This article systematically reviews the research status of AMH in the treatment of COPD with TCM and puts forward some thoughts on the existing problems， so as to provide a reference for clinical rational medication and in-depth research.

Progress on risk factors involved in airway mucus hypersecretion in children with community acquired pneumonia / 国际儿科学杂志

Airway mucus hypersecretion is one of the pathological changes in children with community acquired pneumonia（CAP），and affects the severity，progression and prognosis of CAP.Diagnosis of airway mucus hypersecretion currently relies on fiberoptic bronchoscopy. To predict the risk of airway mucus hypersecretion and to take early action to avoid serious consequences such as plastic bronchitis and hypoxia and respiratory failure，the article summarizes the relationship between age，clinical characteristics and laboratory indices and the formation of airway mucus hypersecretion in children with CAP. Among them，age，pathogenic species，fever peak and fever range，neutrophil ratio，C-reactive protein，lactate dehydrogenase，D-dimer，serum 25（OH）D，and some interleukins，interferons，and acquired immune indicators have an early warning effect on the development of airway mucus hypersecretion in children with CAP.

Linggui Zhugantang Treats Chronic Bronchitis in Rats via PLA2-TRPV1/TRPA1 Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect and mechanism of Linggui Zhugantang in treating chronic bronchitis （CB） induced by exposure to cigarette smoke combined with tracheal instillation of lipopolysaccharide （LPS）. MethodSixty SPF-grade SD rats were randomly divided into normal， model， dexamethasone （1 mg·kg-1）， and high-， medium-， and low-dose （30.06， 15.03， 7.515 g·kg-1， respectively） Linggui Zhugantang groups by the body weight stratification method， with 10 rats in each group. Each group was administrated with 200 μL LPS （1 g·L-1） by tracheal instillation on days 1 and 14， respectively， while the normal group was administrated with an equal volume of normal saline. Except the normal group， the other groups were exposed to cigarette smoke on days 2-13 and 15-30 （10 cigarettes/time/30 min， twice/day） for the modeling of CB. The rats were administrated with corresponding drugs by gavage for 30 consecutive days from day 2 of modeling， and the mental status， behavior， and body weights of the rats were observed and measured. The wet/dry mass ratio （W/D） of the left lung was measured 30 days after modeling. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung and bronchial tissues. The bronchial mucus secretion and goblet cell proliferation were observed by Alcian blue-periodic acid Schiff （AB-PAS） staining. The levels of mucin 5AC （MUC5AC）， interleukin （IL）-13， IL-6， and tumor necrosis factor （TNF）-α in the serum were determined by enzyme-linked immunosorbent assay. The expression of phospholipase A2 （PLA2）， transient receptor potential vanilloid receptor 1 （TRPV1）， and transient receptor potential ankyrin 1 （TRPA1） in the lung tissue was quantitatively analyzed by immunohistochemistry and Western blot. ResultCompared with the normal group， the model group showcased abnormal mental status and behaviors， bloody secretion in the nose and mouth， the mortality rate of 40%， decreased body weight， severe lung bronchial structure damage， a large number of inflammatory mediators and inflammatory cell infiltration in the tube wall， hyperemia， edema， and fibroplasia， massive proliferation of goblet cells， excessive secretion and accumulation of mucus， stenosis and deformation of the lumen， and aggravation of pulmonary edema （P<0.01）. In addition， the model group had higher levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and higher expression of PLA2 in the lung tissue than the normal group （P<0.01）. Compared with the model group， the medication groups showed normal mental status and behaviors， reduced mortality rate， stable weight gain， reduced lung and bronchial injuries， decreased goblet cell proliferation and mucus secretion， and alleviated pulmonary edema （P<0.01）. Furthermore， Linggui Zhugantang lowered the levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and down-regulated the protein levels of PLA2， TRPV1， and TRPA1 in the lung tissue （P<0.01）. ConclusionLinggui Zhugantang can reduce the pulmonary inflammation and airway mucus hypersecretion in the rat model of chronic bronchitis. It may exert the effects of reducing inflammation and resolving phlegm by regulating the PLA2-TRPV1/TRPA1 pathway.

Effect of Bufei Yishen Prescription on Airway Mucus Hypersecretion and Notch3 and HES1 Expression in Lung Tissues of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

ObjectiveTo observe the effects of Bufei Yishen prescription on airway mucus hypersecretion and Notch signaling pathway related protein Notch3 and enhancer of split homologue 1 （HES1） in rats with chronic obstructive pulmonary disease （COPD） and to explore its action mechanism. MethodForty-eight SD rats were randomly divided into the control group， model group， Bufei Yishen prescription group， and aminophylline （APL） group，with 12 rats in each group. The stable COPD rat model was established via cigarette smoking exposure combined with Klebsiella bacterial infection for 12 weeks， and the corresponding drugs （3.7 g·kg-1·d-1 Bufei Yishen prescription and 54 mg·kg-1·d-1 APL） were administered by gavage during the next eight weeks. After the last administration at week 20， the lung tissue was sampled for observing the pathological changes and the rat lung function was detected. The tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and mucoprotein 5AC （MUC5AC） in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues were assayed. ResultCompared with the control group， the model group exhibited significantly weakened pulmonary function （P<0.05，P<0.01）， reduced average number of alveoli （P<0.01）， elevated mean linear intercept （P<0.01）， and up-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and Notch3， HES1， and MUC5AC mRNA and protein expression in lung tissue （P<0.05，P<0.01）. Compared with the model group， Bufei Yishen prescription and APL remarkably enhanced pulmonary function， alleviated its pathological injury （P<0.05，P<0.01）， and down-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues （P<0.05，P<0.01）. ConclusionThe mechanism of Bufei Yishen prescription in inhibiting airway mucus hypersecretion of COPD rats was related to its regulation of Notch3 and HES1.

Experimental study of the effects of Yunpi-Xiefei-Huatan Decoction on the expression of EGFR and MUC5AC in lung tissue of asthmatic rat model / 国际中医中药杂志

Objective:To observe the effect of Yunpi-Xiefei-Huatan Decoction on airway mucus hypersecretion of asthmatic rats and its regulation on epidermal growth factor receptor (EGFR) / mucin 5AC (MUC5AC) signal pathway. Methods:Seventy SD rats were randomly divided into normal group, model group, high dose group, medium dose group, low dose group, western medicine group and combined group, with 10 rats in each group. Except the normal group, the other groups were sensitized with 1 ml ovalbumin and aluminum hydroxide mixture to establish the asthma rat model. On the 16th day of the experiment, the high, medium and low dose groups were given Yunpi-Xiefei-Huatan Decoction of 40, 20, 10 g/kg, respectively, the western medicine group was given carboxymethylstein tablets of 150 mg/kg, and the combined group was given Yunpi-Xiefei-Huatan Decoction of 20 g/kg and carboxymethylstein tablets of 150 mg/kg, once a day, for 4 weeks. The levels of tumor necrosis factor (TNF-α) and interleukin-13 (IL-13) in serum of rats were detected by Enzyme-linked Immunosorbent Assay (ELISA), the total number and classification of leukocytes in BALF were observed by Wright Giemsa staining, the pathological changes of lung tissue were observed by glycogen staining (PAS). The protein expression of epidermal growth factor receptor (EGFR) and MUC5AC (MUC5AC) were detected by Western blotting, and the mRNA expression of EGFR and MUC5AC was detected by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Results:Compared with the model group, the level of IL-13 and TNF-α in the high, medium and low dose groups of traditional Chinese medicine, western medicine group and combined group was significantly decreased ( P<0.05). The levels of WBC, eosinophils and neutrophils in rat alveolar lavage fluid were significantly decreased ( P<0.05). The expression of EGFR (0.466 ± 0.023, 0.354 ± 0.047, 0.667 ± 0.066, 0.553 ± 0.065, 0.290 ± 0.033 vs. 0.782 ± 0.047) and MUC5AC (0.424 ± 0.022, 0.313 ± 0.033, 0.603 ± 0.051, 0.495 ± 0.041, 0.243 ± 0.024 vs. 0.806 ± 0.090) significantly decreased ( P<0.05), the m RNA expression of EGFR (2.302 ± 0.321, 2.549 ± 0.623, 3.084 ± 0.453, 2.585 ± 0.314, 1.810 ± 0.379 vs. 4.101 ± 0.567), MUC5AC (3.243 ± 0.742, 3.283 ± 1.064, 4.419 ± 0.572, 3.817 ± 0.637, 2.469 ± 0.424 vs. 5.840 ± 0.661) in the high, medium and low dose groups, western medicine group and combined group was significantly decreased ( P<0.05). Conclusion:Yunpi-Xiefei-Huatan Decoction ccould inhibit asthma, and its mechanism mightbe related to the EGFR/MUC5AC signaling pathway.

Effects of Qingjin Huatan Decoction on EGFR/MAPK Signaling Pathway of Airway Mucus Hypersecretion Rats with Chronic Obstructive Pulmonary Disease / 中国中医药信息杂志

Objective To observe the effects of Qingjin Huatan Decoction on EGFR/MAPK signaling pathway of airway mucus hypersecretion rats with chronic obstructive pulmonary disease (COPD). Methods Intratracheal instillation of LPS combined with smudging method was used to establish COPD airway mucus hypersecretion rat models. Experimental rats were randomly divided into blank group, model group, Qingjin Huatan Decoction group and clarithromycin group. The blank group was normally fed, while the other three groups were given NS, Qingjin Huatan Decoction, and clarithromycin respectively for gavage, once a day for 30 days. All rats were killed on the 31st day, and pathological changes of lung tissue and mucous glands hyperplasia were observed by HE staining method. The gene expressions of EGFR and MUC5AC in lung tissue were detected by RT-PCR method. The protein expressions of P-EGFR, P-ERK, P-JNK, P-p38 and MUC5AC in pulmonary tissue and airway epithelium were detected by immunohistochemical method. Results Compared with the blank group, mucous glands hyperplasia on airway epithelium, protein expressions of P-EGFR, P-ERK, P-JNK, P-p38 and MUC5AC on airway epithelium significantly increased in the model group (P<0.01); gene expression of MUC5AC of lung tissue increased (P<0.05). Compared with the model group, mucous glands hyperplasia on airway epithelium, P-p38, P-ERK and MUC5AC protein expression on airway epithelium in Qingjin Huatan Decoction group significantly decreased (P<0.05, P<0.01); the protein expression of P-JNK increased significantly (P<0.01). EGFR and MUC5AC mRNA in lung tissue in Qingjin Huatan Decoction group decreased significantly (P<0.01). Conclusion Qingjin Huatan Decoction can reduce airway mucus hepersecrection of COPD by inhibiting ERK and p38 signal pathway on EGFR downstream.

Effects ofJiedu QingfeiMixture on Expressions of NE and MUC5AC in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease / 中国中医药信息杂志

Objective To explore the mechanism ofJiedu Qingfei Mixture for airway mucus hypersecretion of rat models with chronic obstructive pulmonary disease (COPD).Methods Airway instilling lipopolysaccharide combining fuming method was used to establish COPD models. Forty clean level Wistar strain rats were randomly divided into blank control group, model group,Jiedu Qingfei group, and clarithromycin group. Model group, Jiedu Qingfei group, and clarithromycin group were given normal saline,Jiedu Qingfei Mixture, and clarithromycin by gavage respectively, while the blank control group was raised normally for 30 d. All rats were killed on the 31st day for taking lung tissue (6 rats from each group were chosen randomly). Pathological changes of lung tissue and mucous glands hyperplasia were observed by HE staining method. NE and MUC5AC mRNA expression on lung tissue were detected by RT-PCR method. Protein expressions of NE and MUC5AC on pulmonary tissue and airway epithelium were detected by immunohistochemical method.Results Compared with blank control group, mucous glands hyperplasia on airway epithelium, mRNA expression of NE and MUC5AC in lung tissue, and protein expressions of NE and MUCA5C on airway epithelium in the model group significantly increased (P<0.05,P<0.01). Compared with model group, mucous glands hyperplasia on airway epithelium inJiedu Qingfei group significantly decreased (P<0.01), as same as clarithromycin group;Jiedu Qingfei group showed better effects on down-regulating NE and MUC5AC mRNA expression in lung tissue compared with clarithromycin group. MUC5AC protein expression on airway epithelium inJiedu Qingfei group significantly decreased (P<0.05), as same as clarithromycin group.Jiedu Qingfei group and clarithromycin group had no difference on NE protein expression in airway epithelium compared with model group.Conclusion Jiedu Qingfei group Mixture can reduce airway mucus hypersecretion of COPD by down-regulating MUC5AC expression through neutrophil elastase.