Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Using trace elements of magnetite to constrain the origin of the Pingchuan hydrothermal low-Ti magnetite deposit in the Panxi area, SW China

The Pingchuan iron deposit, located in the Yanyuan region of Sichuan Province, SW China, has an ore reserve of 40 Mt with ~60 wt% Fe. Its genesis is still poorly understood. The Pingchuan iron deposit has a paragenetic sequence of an early Fe-oxide–Pyrite stage(Ⅰ) and a late Fe-oxide–pyrrhotite stage(Ⅱ). Stage Ⅰ magnetite grains are generally fragmented, euhedral–subhedral, largesized crystals accompanying with slightly postdated pyrite.Stage Ⅱ magnetite grains are mostly unfragmented, anhedral, relatively small-sized grains that co-exist with pyrrhotite. Combined with micro-textural features and previously-obtained geochronological data, we consider that these two stages of iron mineralization in the Pingchuan deposit correspond to the Permian ELIP magmatism and Cenozoic fault activity event. Both the Stage Ⅰ and Ⅱ magnetites are characterized with overall lower contents of trace elements(including Cr, Ti, V, and Ni) than the ELIP magmatic magnetite, which suggests a hydrothermal origin for them. ‘‘Skarn-like'' enrichment in Sn, Mn, and Zn in the Stage Ⅰ magnetite grains indicate significant material contributions from carbonate wall-rocks due to water–rock interaction in ore-forming processes. Stage Ⅱ magnetite grains contain higher Mn concentrations than Stage Ⅰ magnetite grains, which possibly implies more contribution from carbonate rocks. In multiple-element diagrams, the Stage Ⅰ magnetite shows systematic similarities to Kiruna-type magnetite rather than those from other types of deposits. Combined with geological features and previous studies on oxygen isotopes, we conclude that hydrothermal fluids have played a key role in the generation of the Pingchuan low-Ti iron deposit.

Effect of Pingchuan granule on typeⅡinnate lymphocytes and M2 polarization of macrophages in asthmatic mice

Objective:To observe the effect of Pingchuan granule on the number of typeⅡinnate lymphocytes(ILC2)and M2 polarization of macrophages in the lung tissue of asthmatic mice;Methods:Ovalbumin sensitized and challenged asthmatic mouse models were established,and then Pingchuan granules or IL-33 neutralizing antibody were given to intervene.The pathological morphology of lung tissue was observed by HE,PAS and Masson staining,and the expressions of IL-4,IL-5,IL-13 and IL-33 in BALF and lung tissue were detected by ELISA and qRT-PCR,Flow cytometry was used to detect the number of type II innate lymphocytes and type M2 macrophages in lung tissue.Western blot was used to detect the protein expression levels of ST-2,FIZZ1 and Arg-1 in lung tissue;Results:Compared with the control group,the inflammation score,PAS score and collagen staining area of the model group were significantly increased,the expressions of IL-4,IL-5,IL-13 and IL-33 in BALF and lung tissue were significantly increased,the number of ILC2 and M2 macrophages,the expression of ST-2,FIZZ1 and Arg-1 protein in lung tissue were significantly increased,and the differences were statistically significant(P<0.05);Compared with the model group,Pingchuan granule could significantly reduce the inflammation score,PAS score and collagen staining area of asthmatic mice,down-regulate the expression of IL-4,IL-5,IL-13 and IL-33 in BALF and lung tissue,reduce the number of ILC2 and M2 macrophages,and the expression of ST-2,FIZZ1 and Arg-1 protein in lung tissue(P<0.05);Conclusion:Pingchuan granule improve the airway remodeling of asthma by inhibiting the polarization of M2 macrophages mediated by ILC2.

Clinical Study of Acupoint Application of Jiezi Fangxiao Ointment Combined with Pingchuan Prescription in the Treatment of Pediatric Asthma

[Objectives]To study the clinical effect of Acupoint Application of Jiezi Fangxiao Ointment combined with Pingchuan Prescription in the treatment of pediatric asthma.[Methods]A total of 40 children with asthma admitted to the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2017 to September 2018 were selected as the research subjects,and divided into control group and observation group according to random classification method,with 20 cases in each group.Among which the control group was given routine symptomatic treatment,the observation group was treated with Acupoint Application of Jiezi Fangxiao Ointment combined with Pingchuan Prescription on the basis of the control group.After 4 weeks of continuous treatment,the clinical efficacy was observed and the changes of traditional Chinese medicine symptom scores,forced expiratory volume in the first second(FEV1),maximum expiratory flow(PEF),forced vital capacity(FVC),peripheral blood eosinophils(EOS)and interleukin-17(IL-17)were compared between the two groups before and after treatment.[Results]After treatment,the traditional Chinese medicine(TCM)scores such as asthma,cough,expectoration,chest tightness,dyspnea and wheezing sound of lungs in the two groups were significantly improved,and the improvement in the observation group was superior to that in the control group.The difference was statistically significant(P<0.05).FEV1,PEF and FVC in the two groups were significantly improved after treatment,and the improvement in the observation group was superior to that in the control group.The difference was statistically significant(P<0.05);after treatment,the levels of EOS and IL-17 decreased in both groups,and the improvement in the observation group was superior to that in the control group,the difference was statistically significant(P<0.05).[Conclusions]The clinical effects of Acupoint Application of Jiezi Fangxiao Ointment combined with Pingchuan Prescription in the treatment of infantile asthma were obvious,which can significantly improve the TCM symptoms scores,pulmonary function and immune function of patients.

Clinical Observation of Huagai Pingchuan Decoction Combined with Seretide in the Treatment of Asthma

Objective:To study the clinical effect of the Huagai Pingchuan decoction combined with Seretide in the treatment of asthma.Methods:138 cases of asthma patients in our hospital were separated into the control group and the experimental group.The control group was given Seretide alone,while the experimental group was treated with Huagai Pingchuan decoction combined with Seretide.Results:After treatment,the wheezing symptoms remission time of the experimental group was shorter than control group,the performance of serum inflammatory factors and lung function indexes were better than control group,P<0.05 with significant difference.Conclusion:Huagai Pingchuan decoction combined with Seretide is more effec-tive in the treatment of asthma.

Pingchuan formula(平喘方) improves allergic asthma in mice through inhibiting nuclear factor-kappa B/mitogen-activated protein kinase signaling pathway

OBJECTIVE:To examine the role and decipher the mechanism of Pingchuan formula(平喘方,PCF)in treating allergic asthma.METHODS:The mice were treated with saline,dexamethasone(DXM)and PCF for 1 week after the asthma model was established and their respiratory function including respiratory resistance(RI),pulmonary dynamic compliance(Cdyn)and maximum voluntary ventilation(MVV)were measured.In addition,cellular changes in bronchoalveolar lavage fluid(BALF)and pathological changes in lung biopsy as well as the expression level ofα-smooth muscle actin(α-SMA),transforming growth factor-beta1(TGF-β1)in BALF and interleukin-5(IL-5),interleukin-13(IL-13),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),nuclear factor-kappa B-p65(NF-κBp65),inhibitor-αof nuclear transcription factorκB(IκBα),p38 mitogen-activated protein kinase(p38 MAPK),c-jun n-terminal kinase(JNK)and its phosphorylated proteins in lung tissue were also examined and compared among different groups.RESULTS:Our data suggested that the respiratory functions were significantly improved and the pathological changes ameliorated in the DXM group and the PCF group compared to the model group.Both DXM and PCF effectively decreased the number of eosinophils,lymphocytes,and neutrophils in BAL as well as the secretion ofα-SMA and TGF-β1,IL-5,IL-13,while increased the expression of TNF-αand IFN-γ.Furthermore,our study indicated that the NF-κBp65,IκBα,p38 MAPK and JNK pathways were inhibited under the treatment of PCF.CONCLUSION:Our data indicated that PCF can attenuate the inflammatory response in asthma through inhibiting the NF-κB/MAPK signaling pathway.This study not only supported the use of PCF in allergic asthma in clinic but also shed light upon afurther understanding of the disease pathogenesis.

Randomized Controlled Trial on Treatment of Bronchial Asthma of Qi-deficiency Cold Syndrome Type by Pingchuan Yiqi Granule (平喘益气颗粒)

Objective： To evaluate the effect and safety of Pingchuan Yiqi Granule （平喘益气颗粒, PYG） in treating bronchial asthma of qi-deficiency cold syndrome type （BS-QDC）. Methods： With the randomized, positive agent parallel controlled design adopted, the 80 subjects enrolled were assigned in the ratio of 3：1 to two groups, the 60 patients in the trial group were treated with PYG and the 20 in the control group treated with Ruyi Dingchuan Pill （如意定喘丸,RDP）, with the therapeutic course consisting of 7 days for both groups. The clinical effects, effects on TCM syndrome and the changes of lung function after treatment were observed. Results： The effect of the treatment on asthma in the trial group： clinically controlled rate was 6.67%, markedly effective rate 51.67%, improved rate 33.33% and ineffective rate 8.33%; and the corresponding rates in the control group were 5.00%, 50.00%, 30.00%, and 15.00% respectively. Comparison between the two groups showed insignificant difference （P〉0.05）. The effect on TCM syndrome in the treated group： clinically controlled rate was 11.67%, markedly effective rate 58.33%, effective rate 21.67% and ineffective rate 8.33%; and those in the control group were 10.00%, 50.00%, 30.00% and 10.00% respectively, also showing insignificant difference between the two groups （P〉0.05）. Lung function test showed that the change on forced expiratory volume in 1 second （FEV1） after treatment in the trial group was of statistical significance （P〈0.05）, but no significant difference was shown in the change of peak expiratory flow （PEE P〉0.05）; while the changes in the control group were just the opposite, showing insignificance in FEV1 （P〉0.05） but significance in PEF （P〈0.05）. Comparison of the therapeutic effect on lung function between the two groups showed no significant difference （P〉0.05）. No adverse reaction was found in either group in the course of treatment. Conclusion： PYG used to treat BS-QDC is effective and safe, it＇s effect is similar to that of RDP.