Therapeutic effect of emodin on constipation induced by loperamide in mice

AIM: To study the therapeutic effect of emodin on loperamide-induced constipation in mice. METHODS: The constipation model of mice was established by lopebutamine treatment, and the effects of emodin on defecation frequency, fecal water content and intestinal transit time of the mice during the observation period were detected. Inflammatory infiltration in colon tissue of the mice was observed by HE staining. Serum nitric oxide (NO) content was detected by commercially available kit. The expression of vasoactive intestinal peptide receptor 1 (VIPR1) and 5-hydroxytryptamine type 4 receptor (5-HT₄ receptor) in mouse colon was determined by immunohistochemistry. The effects of emodin on the expression of transient receptor potential cation channel subfamily V member 1 (TRPV1), glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nitric oxide synthase (NOS), c-Kit and their ligand stem cell factor (SCF) were detected by Western blot. RESULTS: Emodin significantly increased the number of defecation and fecal water content in the mice during the observation period, and significantly reduced the intestinal transit time and serum NO level in the mice (P<0.05). The results of HE staining showed that emodin significantly reduced the infiltration of colonic inflammation induced by loperamide. Emodin can significantly reduce the increase in VIPR1 induced by loperamine and increased the expression of 5-HT₄ receptor (P<0.01). Emodin increased the expression levels of GDNF and BDNF, reduced the expression levels of TRPV1 and NOS in the colon tissues of loperamine-induced constipation in mice, and significantly increased the expression of c-Kit and SCF (P<0.05 or P<0.01). CONCLUSION: Emodin promotes the defecation behavior of mice with loperamine-induced constipation by increasing intestinal peristalsis and activating a series of smooth muscle contraction-related factors.     

Effect of arachidonylethanolamide in paraventricular nucleus on cardiac function and sympathetic nerve activity in rats with heart failure

AIM:To determine the roles of the arachidonylethanolamide (AEA) in the paraventricular nucleus (PVN) in cardiac function and sympathetic activity in the rats with chronic heart failure (CHF). METHODS:Chronic heart failure was induced by left coronary ligation in Wistar rats and was confirmed using echocardiography. The rats with CHF and the sham-operated controls (sham group) were treated for 4 weeks with a continuous PVN infusion of AEA, cal-cium-calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) selective inhibitor KN-93, transient receptor potential vanilloid type 1 (TRPV1) channel blocker capsazepine (CPZ), intracellular calcium chelator BAPTA-AM, small-conductance calcium-activated potassium channel (SK channel) blocker apamin and artificial cerebrospinal fluid (vehicle). Sympathetic drive indexes and cardiac function were detected. NG108 cells were incubated with AEA, and then the intracellular cal-cium concentration was measured by fluorometry. The protein expression levels of CaMKⅡ, SK₂ and phosphorylated TRPV1 were determined by Western blot. RESULTS:Compared with sham group, the left ventricular end-diastolic pressure (LVEDP) increased significantly, while peak rate of rise/decline of left ventricular pressure (±dp/dt_max) and ejection fraction (EF) decreased significantly in the CHF group. The concentrations of AEA and intracellular calcium, and the protein levels of CaMKⅡ, SK₂ and phosphorylated TRPV1 in PVN were significantly lower in CHF rats. Compared with the vehicle group, the mortality and sympathetic drive were decreased significantly and cardiac function was improved after treatment with AEA in CHF group. However, PVN perfusion of KN-93, CPZ, BAPTA-AM or apamin contributed to the sympathetic drive and deteriorated the cardiac function. AEA dose-dependently increased intracellular calcium ion concentration, and the protein levels of CaMKⅡ, SK₂ and phosphorylated TRPV1 in NG108 cells. CONCLUSION:AEA in the PVN may be involved in the improvement of cardiac function and sympathetic overdrive via CaMKⅡ/TRPV1/Ca²⁺/SK₂ pathway in rats with CHF.     

Propofol inhibits LPS-induced inflammatory response in microglia via TRPV1 ion channels

AIM:To investigate the effects of propofol (P) on the inflammatory response of microglia induced by lipopolysaccharide (LPS) and the mechanisms. METHODS:Mouse microglia BV2 cells were treated with LPS at 100 μg/L to establish a neuroinflammatory injury model. The BV2 cells were divided into 4 groups:control group (C group), model group (L group), L+P group and LPS+AMG517 group (L+A group). The level of tumor necrosis factor-α (TNF-α) in the cell culture supernatant was measured by ELISA. The mRNA expression of transient receptor potential cation channel subfamily V member 1 (TRPV1) was detected by real-time PCR. The protein levels of TRPV1, TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6) and phosphorylated calcium/calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ) were determined by Western blot. The content of free Ca²⁺ in the microglia BV2 cells was detected by Fluo-3 AM assay. RESULTS:Compared with C group, the level of TNF-α was significantly increased in L group (P<0.01), but that in P group was not changed. Compared with L group, the level of TNF-α was significantly lower than that in L+P group within 4 h (P<0.01). Compared with C group, the mRNA expression of TRPV1 was significantly increased in L group (P<0.01). Compared with L group, the mRNA expression of TRPV1 was significantly down-regulated in L+P group (P<0.01).Compared with L group, the protein levels of TNF-α, IL-1β, IL-6 and p-CaMKⅡ and intracellular Ca²⁺ concentration were significantly lower than those in L+P group and L+A group (P<0.01). CONCLUSION:Propofol inhibits the inflammatory response of microglia by reducing the expression of TNF-α, IL-1 and IL-6, which may be related to the down-regulation of TRPV1 and p-CaMKⅡ and the reduction of intracellular Ca²⁺ concentration.     

Histamine receptor antagonist prevent and ameliorate airway remodeling and acid-base imbalance in asthma of guinea pig

AIM:To investigate the effect of histamine receptor antagonist on airway remodeling and acid-base imbalance in asthma of guinea pig. METHODS:Guinea pigs were divided into 5 groups: the normal control group, the asthma model group, the continued asthma model group, histamine group and histamine receptor antagonist group. For each group, the content of histamine, Na+, Cl-, PaO2, PaCO2, pH, AB, SB in serum, and thickness of airway mucosa and smooth muscle cell layer were measured and compared with each other. RESULTS:(1) According to the content of histamine in serum and thickness of airway mucosa and smooth muscle, the order was: the histamine group>continued asthma model group>the asthma model group>the normal control group (P<0.01), and the histamine receptor antagonist groupthe continued asthma model group (P<0.01), but for PaCO2, the order was conversed. Airway remodeling, increase in histamine in serum, respiratory acidosis and metabolic acidosis in asthmatic guinea pig were observed. Exogenous histamine accentuated the change, however, histamine receptor antagonist attenuated it. CONCLUSION:Histamine may take part in the airway remodeling of asthma. Histamine receptor antagonist can prevent and ameliorate airway remodeling and acid-base imbalance in asthma of guinea pig.     

Polymorphisms in IL-4 and IL-4R genes in children with allergic asthma

AIM: To determine whether interleukin 4 and interleukin 4 receptor α chain are associated with allergic asthma in children and to study the impact of such polymorphism upon plasma IgE.METHODS: Two polymorphism sites of IL-4 and IL-4R were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).RESULTS: (1)The results showed that the IL-4 promoter -589 was not associated with children allergic asthma, however, the IL-4R α chain 576RR genotype and R allele were significantly increased in the subjects with asthma in children compared with age-matched control subjects (χ2=11.84, P＜0.01; χ2=13.03, P＜0.01). The IL-4R α chain 576RR genotype was associated with higher plasma IgE. CONCLUSION: These date suggest that the IL-4R α chain R576 is a risk factor of allergic asthma in children in Chinese, and is also related with higher plasma IgE level.     

Changes in endothelin-1 and atrial natriuretic factor and the effect of atrial natriuretic factor on the change of endothelin-1 in asthmatic guinea pigs

AIM: To investigate the possible role of endothelin(ET-1) in asthma pathogenesis and the effect of atrial natriuretic factor (ANF) on changes of ET-1. METHODS: Measuring the contents of endothelin-1(ET-1),atrial natriuretic factor(ANF),cGMP in plasma and bronchoalveolar lavage fluid (BALF) of guinea pigs. RESULTS: The contents of ET-1, ANF and cGMP in asthma group were higher than that of the control group; There was a significant negative correlation between ET-1 and ANF( r=-0.638,P <0.05) in plasma of the asthma group, and a significantly negative correlation between ET-1 and ANF( r=-0.921,P <0.01) in BALF of the asthma group. There was a significantly positive correlation between ANF and cGMP( r=0.848,P <0.01) in plasma of the asthma group,and a significantly positive correlation between ANF and cGMP ( r=0.831,P <0.01) in BALF of the asthma group. The levels ET-1 in the asthma+rat ANF(rANF) group were lower than those in the asthma group,and the levels of cGMP in the asthma+rat ANF(rANF) group were higher than those in the asthma group after ceasing to infuse rANF for guinea pigs for 30 minutes.CONCLUSION: ET-1 might play an important role in the pathogenesis of asthma.ANF might inhibit production of ET-1.     

Isorhamnetin inhibits ovalbumin-induced pulmonary inflammation in asthmatic mice

AIM To investigate the effect of isorhamnetin on pulmonary inflammation in asthmatic mice and to analyze its primary mechanism. METHODS BALB/c mice were randomly divided into normal control group, asthma model group, isorhamnetin low-dose （50 mg/kg） treatment group and isorhamnetin high-dose （150 mg/kg） treatment group. Ovalbumin （OVA） was used to establish a mouse asthma model. HE staining and PAS staining were used to observe the pathological changes of lung tissue. The contents of cysteinyl leukotriene1 （CysLT1）, cystelinyl leukotriene receptor 1 （CysLTR1）, interleukin-4 （IL-4）, IL-5, IL-13 and tumor necrosis factor-α （TNF-α） in bronchoalveolar lavage fluid （BALF） were measured by ELISA. The expression of nuclear factor of activated T cells 4（NFATc4） in lung tissue was detected by immunohistochemical staining. The protein expression of NFATc4, intercellular cell adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule-1 （VCAM-1） was determined by Western blot. RESULTS Isorhamnetin improved histopathological changes in OVA-induced asthma model mice, reduced the contents of CysLT1, CysLTR1, IL-4, IL-5, IL-13 and TNF-α in BALF, and reduced NFATc4, ICAM-1 and VCAM-1 expression in lung tissue （P<0.05）. CONCLUSION Isorhamnetin inhibits the inflammatory response of lung tissue in asthmatic model mice, and the mechanism may be related to the inhibition of the calcineurin/NFATc4 signaling pathway.     

Effect of TRPV1 activation on lipopolysaccharide-induced lung inflammatory injury in mice

AIM:To investigate the effects of transient receptor potential cation channel subfamily V member 1 (TRPV1) activation by capsaicin on the inflammation and its underlying mechanisms in lipopolysaccharide (LPS)-induced lung injury in mice. METHODS:A total of 108 specific pathogen-free male ICR mice were randomly divided into 6 groups: normal control group, capsaicin (CAP) control group, capsazepine (CAPZ) control group, endotoxemia group, CAP treatment group and CAPZ treatment group. LPS was intraperitoneally injected 30 min after the subcutaneous injection of CAP or CAPZ. After modeling, the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-10, substance P (SP) and calcitonin gene-related peptide (CGRP) in the lung were measured by ELISA. The expression of Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) in the lung tissue was assessed by Western blotting. The pathological changes of the lung tissue were observed under light microscope. RESULTS:The expression of TNF-α, IL-6, IL-10 and NF-κB in the lung tissues at 3 h, 8 h and 16 h was dramatically higher in endotoxemia group than that in normal control group. Compared with endotoxemia group, the levels of TNF-α, IL-6 and nuclear NF-κB in CAP treatment group at 3 h, 8 h and 16 h were obviously decreased, but the level of IL-10 was increased. The changes of the factors mentioned above in CAPZ treatment group were absolutely adverse to those in CAP treatment group. The levels of SP and CGRP were significantly higher in endotoxemia group and CAP control group than those in normal control group, but those in CAPZ control group were lower. Compared with endotoxemia group, SP and CGRP were markedly increased in CAP treatment group and were obviously decreased in CAPZ treatment group. The level of TLR4 in endotoxemia group was distinctly higher than that in normal control group at 3 h, 8 h and 16 h. However, as compared with endotoxemia group, the expression of TLR4 in CAP treatment group and CAPZ treatment group didn’t change much. At 8 h and 16 h after modeling, the degree of lung damage was also decreased in CAP treatment group as compared with endotoxemia group, while that in CAPZ treatment group was aggravated. CONCLUSION: TRPV1 activation obviously inhibits the increase in TNF-α, IL-6 and NF-κB in the lung tissue of endotoxemia mice, and promotes the increase in the anti-inflammatory factor IL-10, as well as the levels of SP and CGRP, but has no effect on the expression of TLR4.     

Expression of VDUP1 in peripheral eosinophil of asthmatic patients and its relation with eosinophil activation

AIM: To investigate the expression of vitamin D3 up-regulated protein 1 (VDUP1) in peripheral eosinophils of asthma patients and its relation with eosinophil activation.METHODS: 10 normal volunteers and 31 mild to moderate asthma patients were selected. Symptom severity, pulmonary function index, induced sputum eosinophil counts were recorded. Then, gene and protein expressions of VDUP1 and β-actin were evaluated by RT-PCR and Western blotting, respectively. In addition, eosinophils were incubated with IL-5, both VDUP1 and β-actin were amplified by RT-PCR. The eosinophil cationic protein (ECP) of supernatant and serum were also detected by ELISA assay. RESULTS: There was a significant decrease in expression of VDUP1 in asthma attack patients without treatment compared with normal volunteers and patients in remission. In contrast, no significant difference between the patients in remission and normal volunteers was observed. In patients with asthma attacks, a negative relationship between expression intensity of VDUP1 and EOS% in induced sputum and serum ECP concentration was also observed. The expression of VDUP1 in eosinophils was decreased by IL-5 stimulation, simultaneously, the ECP in supernatant was increased. CONCLUSION: The expression of VDUP1 in eosinophils decreases in asthma patients, and is negatively associated with serum ECP and induced sputum EOS%. EOS activation by IL-5 may be related to VDUP1 pathway.     

IgE-FcεRI crosslink accelerates atherosclerosis development in allergic asthmatic mice

AIM:To investigate whether allergic asthma accelerates the development of atherosclerosis in mice related to Th2 cells and interleukin-4 (IL-4), and the roles of activation of macrophages by immunoglobulin E (IgE)-Fc ε receptor I (FcεRI) crosslink during the process. METHODS:Six-week-old ApoE^-/- mice were sensitized and challenged by ovalbumin to establish the allergic asthma model, and then assigned to 3 groups:control group, asthmatic placebo group and asthmatic IL-4 monoclonal antibody (mAb) intervention group (intervention for 8 weeks). The lesion area was measured by oil red O staining. The percentages of Th2 cells in the splenocytes of the mice were analyzed by flow cytometry. The mRNA expression of IL-4 and the macrophage-related inflammatory factors, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and IL-6, in the spleen was detected by real-time PCR. Local IgE and FcεRIα expression in the plaque was evaluated by immunofluorescence/immunohistochemical staining, and the circulating IL-4 and IgE were measured by ELISA. RESULTS:Accompanied by aggravated atherogenesis in asthmatic ApoE^-/- mice, the proportion of Th2 cells and IL-4 mRNA in the spleen, IgE and FcεRIα expression in the aortic root, and the mRNA expression of MCP-1, MIP-1α and IL-6 were markedly increased. After 8-week treatment with IL-4 mAb, the lesion area in the aortic root of asthmatic ApoE^-/- mice was markedly decreased, the elevated IgE and FcεRIα expression was significantly decreased, and the mRNA expression of macrophage-related inflammatory factors was also decreased. CONCLUSION:Allergic asthma accelerates the atherosclerosis in ApoE^-/- mice, which is associated with the increased Th2 cells and IL-4, and the activation of macrophages by IgE-FcεRI crosslink.     

Advance in biological properties of IL-38 and its role in pulmonary diseases

Interleukin-38 （IL-38） is the most recently discovered cytokine of the IL-1 family and is an IL-36 receptor inhibitor. IL-38 is mainly expressed in human immune organs and associated with a variety of diseases. In the process of apoptosis and necrosis caused by injury or inflammation， researchers have studied quiet a lot about the kinase， cleavage sites， activity regulatory mechanism， signal transduction ligand， transduction mode and potential receptors of IL-38， but many mechanisms are still unknown. This article reviews the role of IL-38 in the pathogenesis and progression of lung tumors， asthma and interstitial lung disease. We also discussed the role of IL-38 in the treatment of these diseases， the possible relationship between IL-38 and tuberculosis， and the direction of future studies on the mechanism of IL-38 action.     

Association analysis of FcεRⅠβ gene with allergic asthma in Chinese

AIM: To investigate the linkage between the polymorphism of -109 and Glu237 in the high-affinity IgE receptorβ(FcεRⅠβ) gene and susceptibilty of allergic asthma in adults in a Chinese population. METHODS: Allergic asthma sample in adult and age-and sex-matched control were studied. A-109C/T and a coding variant Glu237Gly in FcεRⅠβ were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: (1)The genotype frequencies were 0.415 for -109T/T, 0.491 for-109T/C and 0.094 for -109C/C in allergic asthma in adults. No significant difference in the distribution of-109C/T polymorphism was found between allergic asthma adult subjects and healthy control subjects. However, a homozygosity for the-109T allele was associated with increased total plasma IgE levels in subjects with allergic asthma (F=7.213, P<0.01). (2)The allele frequency of Gly237 in the patients and control was 0.245 and 0.142, respectively. There was a significant association between Gly/Gly genotype and allergic asthma in adults among allergic asthma patients. Gly237 was significantly associated with high IgE. CONCLUSIONS: It suggests that Gly237 vaviant of the FcεRⅠβ gene is involved in the development of allergic asthma. The-109C/T and Glu237Gly polymorphisms are two of the genetic factors identified, which affects total plasma IgE levels in adult allergic asthma in Han of Hubei province.     

Effects of CpG-oligodeoxynucleotides and dexamethasone on airway remodeling and expression of MMP-9 and TIMP-1 in murine model of chronic asthma

AIM: To observe the changes of airway inflammation and remodeling in a murine model of chronic asthma with CpG- oligodeoxynucleotides(CpG ODN) and dexamethasone (DXM) treatments.METHODS: BALB/c mice were sensitized and repeatedly challenged with ovalbumin.Pathological slides were prepared from left lung and stained with hematoxylin-eosin.WAmus (smooth muscle area),Wamuc (mucous area) and WAi (inner wall area) of the airway were measured and standardized by Pbm (basement membrane perimeter). The areas of collagen Ⅰand Ⅲ in the lung tissue were determined by using a Sirius red-polarizing microscopy morphometry method.Expressions of matrix metalloprotease-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by immunohistochemistry.RESULTS: WAmus/Pbm,WAmuc/Pbm and WAi/Pbm decreased significantly in CpG ODN and DXM treated group when compared with asthma group (P<0.05).No statistical significance between CpG ODN and DXM treated group was observed (P>0.05).Collagen deposition in asthma group increased more than that in CpG ODN and DXM treated group (P<0.05).The expressions of MMP-9 and TIMP-1 were much higher in asthma group than those in CpG ODN and DXM treated group (P<0.05).It had no statistical significance between CpG ODN and DXM treated group (P>0.05).CONCLUSION: Airway remodeling occurrs in the chronic asthma.Early intervention with steroid or CpG might partially inhibit its process via lowering expressions of MMP-9 and TIMP-1 in chronic asthma.     

Effects of ginsenoside Rh1 on expression of inflammatory factors in mouse asthma model

AIM: To observe the effects of ginsenoside Rh1 on the levels of inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), and the pathological changes of the lung tissues in an experimentally induced mouse asthma model. METHODS: Male BALB/c mice (n=40) were divided into 4 groups:normal control group, asthma mo-del group, and low-dose (40 mg·kg^-1·d^-1) and high-dose (80 mg·kg^-1·d^-1) ginsenoside Rh1 groups. The bronchial asthma mouse model was established by the method of ovalbumin induction and excitation, and during the excitation period, the mice were daily treated with ginsenoside Rh1 for 2 weeks. At 24 h after the final dose of ginsenoside Rh1, the mice were sacrificed. The number of eosinophils (EOS) and the concentrations of interleukin (IL)-4, IL-5 and interferon (IFN)-γ in BALF were determined. The levels of IgG and IgE in serum were measured, and the expression of transforming growth factor (TGF)-β1 and the pathological changes in lung tissues were evaluated. RESULTS: Ginsenoside Rh1 inhibited the increases in the number of EOS and the concentrations of IL-4, IL-5, IFN-γ and IgE, reversed the increased expression of TGF-β1, and improved the pathological changes of the lung tissues in asthmatic mice. CONCLUSION: Ginsenoside Rh1 improves the immuno-inflammatory profile and pathological changes in the experimentally induced mouse asthma model, implying its potential therapeutic effect on asthma.     

Ca2+-activated chloride channels and airway mucus overproduction in asthma

Ca2+-activated chloride channels (CaCC, CLCA) are a new family of chloride channels discovered recently, which are related to Ca2+-sensitive chloride ions transport, and there were several members identified currently in different biologic bodies. New studies have shown that its member gob-5 in murine （its human counterpart is CaCC1） plays a pivotal role in airway goblet cell metaplasia, mucus overproduction, MUC5AC gene expression as well as airway hyperresponsiveness (AHR) in asthma, and is a key molecule in the induction of murine asthma and an asthma-related gene. Inhibition of their function and/or their signaling pathway may therefore provide a new therapeutic strategy for asthma.     

Role of calcineurin in airway remodeling in guinea pig model of asthma

AIM:To investigate the role of calcineurin (CaN) in airway remodeling in guinea pig model of asthma.METHODS:Male guinea pigs were randomly divided into three groups: control, asthma group and CsA group. The following parameters were measured: 1. The protein content, cell count and differential count of BALF; 2. The amount of [³H]-TdR incorporation into central airway smooth muscle; 3. The mean thickness of airway wall and airway smooth muscle of small airwaysl; 4.CaN activity of trachea and lung tissue.RESULTS:1. The protein content, cell count and eosinophil of BALF in CsA group were 46%, 51% and 60% lower than those in asthma group, respectively (P＜0.01); 2. [³H]-TdR incorporation in CsA group was 22% lower than that in asthma group (P＜0.05);3. The mean thickness of airway wall and airway smooth muscle were 34% and 37% less in CsA group than those in asthma group, respectively (P＜0.01); 4. CaN activity of lung tissue and trachea were 52% and 44% lower in CsA group than those in asthma group, respectively (P＜0.01).CONCLUSION:CsA reduced airway remodeling in guinea pig model of asthma, indicating the role of CaN in the airway remodeling.     

Effects of eosinophils deletion on sPLA2-X in bronchial asthma model mice

AIM To investigate the association between soluble phospholipase A2-X（sPLA2-X） and eosinophils in bronchial asthma, and to provide new insight and strategies for the treatment of bronchial asthma. METHODS Female Babl/c mice （n=48） of SPF grade and 6~8 weeks old were divided into 4 groups （with 12 in each group： healthy control group,asthma control group, eosinophil deletion group, and asthma /eosinophil deletion isotype control group）. The mouse model of bronchial asthma was constructed. The mice in healthy control group were intraperitoneally injected with saline on days 0, 7, and 14. The mice in other groups were intraperitoneally injected with 50 μg OVA and 2 mg aluminum hydroxide gel（soluble in 200 μL saline.On the 21st d and 26 th d, eosinophil deletion antibody （anti-CCR3） and isotype control were intraperitoneally injected and intranasally respectively, and then the lungs function test was conducted within 48 h after the end of nebulization.Half of the mice in each group were subjected to whole lung lavage, the remaining half were used for lung tissue section with HE staining, the whole blood was used to measure serum IgE, the supernatant of broncho alveolar lavage fluid （BALF） was used to measure cytokines, and total number of cells in the bronchoalveolar lavage fluid was analyzed for cell classification and flow cytometry. RESULTS （1）Compared with asthma control group,the airway and alveolar inflammatory responses in asthma/eosinophil deletion group was significantly alleviated.（2） Compared with asthma control group, anti-CCR3 successfully deleted eosinophils, and the percentage of eosinophils in bronchoalveolar lavage fluid in asthma/eosinophil deletion group was significantly reduced （P<0.05）.（3） The airway hyperresponsiveness in asthma/eosinophil deletion group was significantly decreased as compared with asthma control group（P<0.05）.（4） The levels of sPLA2-X in the serum and BALF was significantly reduced in asthma/eosinophil deletion group as compared with asthma control group（P<0.05）.（5）Compared with asthma control group,the levels of IL-4, IL-5, and IL-13 in the BALF of the mice in asthma/eosinophil deletion group were significantly reduced, and the serum level of IgE was also decreased （P<0.05）. CONCLUSION Eosinophils in bronchial asthma are importantly associated with sPLA2-X.     

Role of neutrophil elastase and myeloperoxidase in asthma of rats

AIM:To observe the changes of polymorphonuclear leukocytes (PMN), neutrophil elastase (NE) and myeloperoxidase (MPO) expression in rat asthma. METHODS:Eighteen rats were randomly divided into two groups on average, including asthma group and control group. The rat model of asthma was established by the ovalbumin (OVA) challenge methods. Blood PMN were isolated andpurified. The protein expression of MPO were detected by immunohistochemistry and chromatometry techniques. NE was detected by ELISA. RESULTS:(1) Immunohistochemistry showed that the levels of MPO expression around bronchus and in purified PMN in asthma group were significantly increased compared with those in control group (P<0.01). Activities of MPO were significantly increased in bronchoalveolar lavage fluid (BALF) and lung tissue in asthma group compared with those in control group (P<0.05, P<0.01). (2) Levels of NE were significantly increased in BALF and PMN in asthma group compared with control group (P<0.01). (3) Number of PMN were significantly higher in BALF, bronchus and lung tissue in asthma group than those in control group (P<0.01). CONCLUSION:Levels of PMN counting and expression of MPO and NEare significantly increased in experimental asthma rats. PMN may be involved in inflammation in asthma via increasing the levels of NE and MPO.