Phosphodiesterase 3 inhibitor attenuates cough response in a sensitized guinea pig model

AIM: To investigate the effects of selective phosphodiesterase 3 inhibitor olprinone on cough response in guinea pigs sensitized and challenged with ovalbumin.METHODS: Forty sensitized guinea pigs were randomly divided into control (n=10), challenged (n=10), olprinone (n=10) and aminophylline group (n=10). Two hours after challenged with the aerosol of 1% ovalbumin or saline, animals were intraperitoneally injected either with saline, 25 mg/kg of olprinone or 25 mg/kg aminophylline. At 24 h, the injection was repeated with 2.5 mg/kg and 25 mg/kg olprinone or 2.5 mg/kg and 25 mg/kg aminophylline respectively in olprinone and aminophylline group, cough response to inhaled capsaicin and airway responsiveness to methacholine (PC150) were measured. Then, total cell number and differential counts were analyzed in bronchoalveolar lavage fluid. RESULTS: The cough frequency was (5±2) times/3 min in control group and (24±3) times/3 min in challenged group (P<0.05), while PC150 was (659±57) mg/L in control group and (238±67) mg/L in challenged group (P<0.05). 25 mg/kg olprinone significantly inhibited the augmented cough response and airway hyperresponsiveness, the cough frequency and PC150 were (15±2) times/3 min and (580±45) mg/L (P<0.05), which differed significantly from (18±2) times/3 min and (438±52) mg/L in aminophilline group (P<0.05). However, olprinone failed to reverse the elevated total cell number and percentage of eosinophils in bronchoalveolar lavage fluid from guinea pigs challenged with ovalbumin (P>0.05).CONCLUSION: Phosphodiesterase 3 inhibitor attenuates cough response associated with eosinophilic airway inflammation by bronchodilatory effect.     

Effect of tachykinin on cough response in an ovalbumin-sensitized guinea pig model

AIM: To investigate the role of tachykinin in airway in cough response in guinea pigs sensitized and challenged with ovalbumin. METHODS: 20 normal and 20 sensitized guinea pigs were challenged with the aerosol of ovalbumin. twenty-four hours later, cough response to inhaled capsaicin was measured after the normal and sensitized guinea pigs (10 of each) introperitoneally injected either with 0.1 mg/kg, 0.3 mg/kg and 1.0 mg/kg of NK1 antagonist SR140333 or NK2 antagonist SR48968, respectively. Specific airway resistance was recorded with noninvasive technique. RESULTS: Cough response increased in sensitized guinea pigs compared with control ［(19.5±5.7） times/3 min vs （9.3±1.2） times/3 min, P<0.05］. SR48968FR decreased the cough response by 30% in control guinea pigs (P<0.05), but SR140333 did not. Both prevented an increase in airway resistance after the inhalation of capsaicin. However, SR48968FR and SR140333 inhibited increased cough response ［(9.9±4.7） times/3 min, （8.0±1.6） times/3 min, P<0.05］ and airway resistance induced by the inhalation of capsaicin. CONCLUSION: Neurokinin (NK) antagonist inhibits increased cough response in guinea pigs sensitized and challenged with ovalbumin. Tachykinin may be an important mediator in cough associated with eosinophilic airway inflammation.     

Effect of BCG on experimental asthma in a guinea pigmodel of allergen sensitization

AIM: To examine the effect of bacillus calmette-guerin (BCG) on experimental asthma in guinea pigs. METHODS: Guinea pigs were sensitized with BCG and then with ovalbumin (ip). Two weeks later, guinea pigs were challenged with ovalbumin (OVA) aerosol inhalation. Thirty one Guinea pigs were divided into three groups at random control group,OVA-treated group, BCG and OVA-treated group.RESULTS: Ovalbumin inhalation caused a marked airway infiltration of eosinophils and all the animals exhibit asthmatic symptoms. Pretreatment with BCG induced typical increase in lymphocytes and monocytes in peripheral blood and in bronchoalveolar lavage fluid (BALF). BCG markedly inhibited eosinophil infiltration and attenuated the asthmatic symptoms. CONCLUSION: These data suggest that BCG exerts an inhibitory effect on asthmatic inflammation.     

Effects of hypoxia inhalation therapy on the number of eosinophil and CD4+T-lymphocyte in remission stage in asthmatic guinea pigs

AIM:To explore the mechanism underlying the therapeutic effects of hypoxia inhalation on asthma. METHODS:Guinea pigs were randomized into the normal group(NG), asthmatic group(AG) and the hypoxia inhalation-treated group(HITG). The model of asthma was established in the latter two groups through sensitization and induction with 10% ovalbumin(OA) and 1% OA, respectively. The animals in HITG were treated with hypoxia inhalation (13.0%±0.5% O₂/N₂ mixed gas). The content of serum cortisol, the number of eosinophils(EOS) and percentage of hypodense eosinophils(HEOS) in bronchoalveolar lavage fluid(BALF),the number of CD₄⁺T-lymphocyte in peripheral blood(PB) and the tension of airway muscle were determined. RESULTS:(1)The content of serum cortisol was significantly higher in NG and HITG than in AG(P＜0.01); (2)The number of EOS and percentage of HEOS in BALF was significantly lower in HITG than in AG(P＜0.01); (3) The number of CD₄⁺T-lymphocyte in PB was significantly higher in AG than in HITG(P＜0.01).CONCLUSION:After treatment with hypoxia inhalation, the content of serum cortisol in asthmatic guinea pigs was significantly increased to result in marked decreased of the number of EOS, the percentage of HEOS in BALF, and the number of CD₄⁺T-lymphocyte in PB, thus result in the tension of airway muscle and alleviation of the airway hyperresponsiveness. All these may be beneficial to preventing the relapse of asthma.     

Therapeutic effects of hypobaric hypoxia on asthma in guinea pigs

AIM:To explore the mechanismof the therapeutic effect of hypobaric hypoxia on allergic asthmas guinea pigs.METHODS:After the model of asthma was established with oval bumin(OA)challenge i n OA sensitized guinea pigs,the ani mals were randomized i nto the asthmas group(AG),the alleviative group(ALG)and hypobaric hypoxiatreated group(HHTG).The levels of plasma cortisol and endothelin(ET),ET in bronchoalveolar lavage fl ui d(BALF)were deter mi ned by radioi mmunoassay.The pul monary pathological changes were observed with optical microscope.RESULTS:(1)Infiltration of eosinophils(EOS)in alveolar septumwas found in AGand ALG,while it was re-duced in HHTG.(2)The level of plasma cortisol was significantly higher in AGthanin normal control group(NCG)(P<0.01).But it was significantly lower in ALGthani n NCG(P<0.01),there was no difference in plasma cortisol level between HHTG and NCG.(3)The content of ET in plasma was significantly higher in ALGthanthat i n NCG,AG and HHTG(P<0.01),and ET level in BALF was significantly higher in AG than that in NCG,ALG and HHTG(P<0.05),however,no significant difference was found among the latter three groups, respectively.CONCLUSION:After the treatment with hypobaric hypoxia,the ET levels of the plasma and BALF were decreaced and the content of plasma cortisol was increaced,and infiltration of EOS in alveolar septum was decreaced in asthmatic gui nea pigs.That may be one of the mechanisms by which hypobavic hypoxia prevents and cures asthma.     

Effects of mitogen activated protein kinase on γ-glutamylcysteine synthase in lung of guinea pigs with bronchial asthma

AIM: To investigate the effects of mitogen activated protein kinase on γ-glutamylcysteine synthase (γ-GCS) in lung of guinea pigs with bronchial asthma.METHODS: Twenty adult male guinea pigs were divided into asthmatic group and control group (10 in each group).Asthmatic model was established by ovalbumin intraperitoneal injection combined with inhalation.The numbers of total and inflammation cells in bronchoalveolar lavage fluid (BALF) were measured.The γ-GCS-h mRNA in lung tissue was examined by in situ hybridization and RT-PCR.Immunohistochemistry was used to detecte the expression of γ-GCS,phosphorylated extracellular signal regulated kinase (p-ERK),phosphrylated c-Jun amino terminal kinase (p-JNK) and phosphorylated p38 (p-p38) in lung tissues.Western blotting was conducted to determine the expressions of p-ERK,p-JNK and p-p38 in lung tissue.The activity of γ-GCS was measured by coupled enzyme assay.RESULTS: (1) The total cell number and number of eosinophils in BALF of asthmatic group were significantly higher than those in control group (P<0.01).(2) Immunohistochemistry indicated that the p-ERK,p-p38,p-JNK and γ-GCS were stronger expressed in asthmatic group than those in control group (P<0.01).Western blotting also discovered that the expressions of p-ERK,p-JNK and p-p38 in lung tissue of asthmatic group were stronger than those in control group.(3) Both in situ hybridization and RT-PCR analysis showed that the expression of γ-GCS-h mRNA was more positive in asthmatic group compared with control group (P <0.01).(4) The activity of γ-GCS of asthmatic group was significantly higher than that in control group (P<0.01).(5) Linear correlation analysis indicated that in lung tissue of guinea pig with asthma,p-ERK and p-p38 markedly positive correlated with γ-GCS-h mRAN and γ-GCS protein.No relationship between p-JNK and γ-GCS-h mRAN,γ-GCS protein was observed.CONCLUSION: The expressions of p-ERK,p-p38,p-JNK and γ-GCS increase in lung of guinea pigs with bronchial asthma.p-ERK and p-p38 may positively regulate the expression of γ-GCS.     

Expression of PPARγ, Nrf2 and γ-GCS-h in inflammatory cells in bronchoalveolar lavage fluid of guinea pigs with bronchial asthma

AIM: To investigate the expression of PPARγ and Nrf2/γ-GCS-h in inflammatory cells in bronchoalveolar lavage fluid(BALF) of guinea pig with bronchial asthma of acute episode, and to explore the roles of PPARγ on Nrf2/γ-GCS-h expression. METHODS: Forty adult male guinea pigs were randomly divided into 4 groups (10 guinea pigs in each group): control group (group A), asthmatic group (group B), dexamethasone treatment group (group C) and rogridone treatment group (group D). The asthmatic model was established by an ovalbumin challenge method. BALF was collected, and the total cell count and the proportion of the inflammatory cells were measured. After centrifugation, the concentrations of ROS and MDA in the clear supernatant were detected. The methods of in situ hybridization and immunohistochemistry were used for detecting the expression of PPARγ and Nrf2/γ-GCS-h at mRNA and protein levels. RESULTS: The proportion of eosinophils (EOS) in BALF in group B was significantly higher than that in groups A, C and D (P<0.01). The concentrations of ROS and MDA in BALF of group B was the highest. The difference of ROS and MDA was statistically significant (all P<0.05) as compared to the control. The results of immunohistochemistry and in situ hybridization indicated that the A value was the lowest in group B as compared to that in groups A, C and D (all P<0.01). In group B, the positive correlations were observed between PPARγ and Nrf2/γ-GCS-h, between γ-GCS-h and Nrf2. A negative correlation between the proportion of EOS in BALF and the expression of PPARγ and Nrf2/γ-GCS-h was also observed (all P<0.05). CONCLUSION: In acute asthmatic models induced by ovalbumin, the expression of PPARγ and Nrf2/γ-GCS-h is decreased, and PPARγ may up-regulate the expression of Nrf2/γ-GCS-h to inhibit the inflammatory and oxidative reactions, indicating a new way for prevention and treatment of bronchial asthma.     

Effect of airway remodeling on airway responsiveness in asthmatic guinea pigs

AIM: To establish a guinea pig asthma model and to evaluate the effect of airway remodeling on airway responsiveness. METHODS: The guinea pig asthma model was established by ovalbumin (OVA) sensitization and challenge repeatedly. Bronchial provocation tests were conducted through intravenous injection of acetylcholine. The airway morphologic parameters were measured by computer image analysis system. White blood cells and the differential count in bronchoalveolar lavage fluid (BALF) were examined. RESULTS: The resistance of airway was increased significantly after 4 weeks of OVA exposure, but the increase disappeared upon prolonged exposure. After 8 weeks of OVA exposure, fiber tissue in large airway was increased, and the thickness of smooth muscle layer of small airway was enlarged, as compared with that in control animals. CONCLUSION: Airway responsiveness has changed after prolonged OVA exposure in guinea pigs. This change is related to airway remodeling.     

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.     

Effects of 5-HT and electrolytes on the airway remodeling of bronchial asthma in guinea pigs

AIM: To explore the effects of 5-HT and electrolytes on the airway remodeling in guinea pigs with bronchial asthma.METHODS: 70 guinea pigs were divided into 7 groups: control group, model group, continued model group, 5-HT group, anti-5-HT group, high Mg2+ group, low Mg2+ group.Remodeling model was established with ovalbumin.RESULTS: ① In model group, 5-HT of serum and thickness of airway walls were significantly increased compared with control group (P<0.05,P<0.01).② In continued model group, 5-HT and thickness of airway walls were significantly increased compared with model group (P<0.05, P<0.01).③ In 5-HT group, thicknesses of airway walls were significantly increased compared with continued model group (P<0.05).④ In anti-5-HT group, thicknesses of airway walls were significantly decreased compared with continued model group (P<0.05).⑤ In high Mg2+ group, thicknesses of airway walls were significantly decreased compared with continued model group (P<0.05).⑥ In low Mg2+ group, thickness of airway smooth muscle was significantly increased compared with continued model group (P<0.05).⑦ With the aggravation or alleviation of airway remodeling, concentration of Ca2+ in serum was upward or downward.However, concentration of PO3-4 was downward or upward.⑧ Veriety of Na+, K+, Cl- was no significant difference among groups.⑨ Concentration of 5-HT in serum was corrected with that of Ca2+.CONCLUSIONS: ① 5-HT mediates airway remodeling of asthma in guinea pigs whereas Mg2+ may play a regulatory role.② Increase in Ca2+ and decrease in PO3+4 may promote the airway remodeling of asthma whereas Na+, K+, Cl- may not play any role.③ Concentration of 5-HT in serum was corrected with that of Ca2+ in airway remodeling of asthma.     

Effect of intranasal treatment with Toll-like receptor 9 ligand CpG oligodeoxynucleotides on airway inflammation in mice with allergic combined airway disease

AIM: To investigate the therapeutic effect of intranasal administration of CpG oligodeoxynucleotides (CpG-ODN), compared with intradermal administration, on lower airway inflammation in ovalbumin (OVA)-induced allergic combined airway disease (ACAD) mouse model.METHODS: Totally 30 female BALB/c mice aged from 6 to 8 weeks were randomly divided into control group, allergic rhinitis model group (AR group), ACAD group, ACAD intranasally treated with CpG-ODN group (CpG i.n. group) and ACAD intradermally treated with CpG-ODN group (CpG i.d. group). The mice were sensitized and challenged with OVA. Treatment with CpG-ODN was also performed during challenge, either intranasally or intradermally. Immunologic variables and nasal symptom were studied.RESULTS: Compared with CpG i.d. group and ACAD group, the percentage of eosinophils from bronchoalveolar lavage fluid (BALF), the levels of Th2 cytokine production in BALF and supernatants of cultured splenic lymphocytes, OVA-specific IgE from blood, peribronchial inflammation score in the lung, and nasal symptoms were significantly reduced in CpG i.n. group.CONCLUSION: Allergic rhinitis treated by CpG-ODN has a significant improvement on lower airway inflammation in ACAD mouse model; and it may be more effective when administrated intranasally than intradermally.     

Effects of M. vaccae on eosinophil apoptosis and Bcl-2 protein expression in lung tissues of asthmatic guinea pigs

AIM: To study the effects of M. vaccae on eosinophil apoptosis and Bcl-2 protein expression in lung tissues of asthmatic guinea pigs. METHODS: 30 guinea pigs were divided into normal saline (NS) group, asthma group and M. vaccae treatment group at random, every group included 10 guinea pigs. Guinea pigs in M. vaccae treatment group were injected intramuscularly with 22.5 μg M. vaccae 10 days before OVA immunization. TdT-mediated dUTP nick end labeling (TUNEL) technique was used to investigate the apoptosis of eosinophils and immunohistochemistry method was used to study the expression of Bcl-2 protein in lung tissues. RESULTS: The apoptosis index (AI) of eosinophils in lung tissues in M. vaccae treatment group was significant higher than that in asthma group ［(23.78±5.42)% vs (4.56±0.68)%, P<0.01］. The mean optical density value of Bcl-2 protein in lung tissues of M. vaccae treatment group was significant lower than that of asthma group ［(1 556.3±492.4) vs (2 321.9±751.2), P<0.05］. CONCLUSION: The apoptosis of eosinophils induced by M. vaccae in lung tissues of asthmatic guinea pigs may be due to the inhibition of Bcl-2 protein expression.     

Protective effects of hypercapnia on acute lung injury and it's mechanisms

AIM: To investigate whether hypercapnia is protective against acute lung injury (ALI) in a rabbit model, and study it's potential mechanisms. METHODS: Twenty-two healthy New Zealand white rabbits were involved in this study, and randomly allocated to control group (group C), normocapnic group (group N) and hypercapnic group (group H). Oleic acid (0.1 mL/kg) was injected intravenously to establish ALI model. Lung mechanics, hemodynamics, blood-gas analysis, the content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in lung tissue were measured. Apoptosis was analyzed after 3h mechanical ventilation. RESULTS: (1) Peak airway pressure in group H was significantly lower than that in group N (P<0.05) and the dynamic lung compliance was significantly higher than that in group N (P<0.05). (2) PaO₂ in group H was significantly higher than that in group N(P<0.05). (3) The content of MDA was significantly lower but the activity of SOD was significantly higher in group H than that in group N (P<0.05). (4) Apoptosis index in group H was significantly lower than that in group N (P<0.01). (5) Histologic damage was significantly severer in group N than group H. (6) PaCO₂ was correlated with pH, PaO₂, dynamic lung compliance, peak airway pressure and pulmonary permeability index (r=－0.928, P<0.01; r=0.511, 0.526, -0.506, -0.556, P<0.05, respectively). CONCLUSION: Hypercapnia protects lung from oleic acid-induced injury in rabbits. The mechanisms of protection might be associated with improvement of oxidation/anti-oxidation imbalance and inhibition of apoptosis.     

Inhibitory effect of ground dragon on the expression of α-SMA and FN in the lung tissue of mouse with asthma

AIM: To investigate the inhibitory effect of ground dragon on the expression of α-SMA and FN in the lung tissue with asthma. METHODS: The BALB/c mice were divided into four groups: control group (group A, n=20), asthmatic model group (group B, n=20), large-dose ground dragon treatment group (group C, n=20) and low-dose ground dragon treatment group (group D, n=20). To establish a mouse model of chronic asthma, we sensitized the mouse with 0.02% ovalbumin (OVA) by intraperitoneal injection, and stimulated the mice with 1% OVA by atomization. The treatment groups were given ground dragon before stimulation every time. After the last time of stimulation, the mice were subjected to laboratory tests. Inflammatory cells in bronchoalveolar lavage fluid were counted. Total level of IgE in serum was detected by ELISA. FN mRNA and α-SMA mRNA in the lung tissue were measured by RT-PCR and AlphaImager 2200 semi-quantitation analysis system. Expressions of FN and α-SMA were measured by the method of two-step immunohistochemistry and leica QWIN V3 analysis system. RESULTS: (1) Compared with those in group A, the expressions of α-SMA and FN in group B were significantly increased (P<0.01). Compared with group B, those in group C were significantly decreased (P<0.01), while those in group D were slightly decreased (P>0.05). (2) Compared with those in group A, the expression levels of α-SMA mRNA and FN mRNA in group B had a great increase (P<0.01). There was a notably decreases of α-SMA mRNA and FN mRNA levels in group C, compared with group B (P<0.01). However, α-SMA and FN mRNA level in group D was just a slightly decreased, compared with group B (P>0.05). CONCLUSION: The ground dragon inhibits α-SMA and FN expression in the lung tissue of mice with chronic asthma, indicating that ground dragon may inhibit airway remodeling in asthma through the inhibition of α-SMA and FN expressions.     

Effects of Maxing-Shigan decoction on airway remodeling and expression of MMP-9 and TIMP-1 in lung tissues of asthmatic mice

AIM:To investigate the effects of Maxing-Shigan decoction on airway remodeling and expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the lung tissues of asthmatic mice, and to explore its possible mechanism in treatment of asthma. METHODS:The BALB/c mice were divided into blank control group, model group, low-dose Maxing-Shigan decoction group, middle-dose Maxing-Shigan decoction group, high-dose Maxing-Shigan decoction group and positive control group. The mice were sensitized and challenged with ovalbumin to establish asthma model. The mice in blank control group and model group were given saline by oral administration before 30 min of suscitation. The mice in low-dose, middle-dose and high-dose Maxing-Shigan decoction groups were given Maxing-Shigan decoction at 5.0 g/kg, 10.0 g/kg and 20.0 g/kg, respectively, by oral administration before 30 min of suscitation. The mice in positive control group was given dexamethasone at 0.005 g/kg by oral administration before 30 min of suscitation. After consecutive administration for 7 d, the variations of airway responsiveness, the percentage of the goblet cells, the collagen deposition, and the eosinophil (EOS) counts in bronchoalveolar lavage fluid (BALF) of each group were observed. The protein levels of MMP-9 and TIMP-1 in the lung tissues were determined by ELISA and Western blot. The mRNA expression of MMP-9 and TIMP-1 was detected by RT-qPCR. RESULTS:Compared with blank control group, the airway responsiveness, the goblet cell percentage, the collagen deposition, the EOS counts in BALF, the protein levels of MMP-9 and TIMP-1, and the mRNA expression of MMP-9 and TIMP-1 were significantly increased in model group (P<0.01). Compared with model group, all of the indexes were reversed in low-dose, middle-dose and high-dose Maxing-Shigan decoction groups and positive control group (P<0.05 or P<0.01). CONCLUSION:Maxing-Shigan decoction improves airway remodeling in asthma model mice by down-regulating the expression of MMP-9 and TIMP-1.     

Effect of hydrogen sulfide on airway inflammation induced by ozone in mice

AIM: To investigate the effect of hydrogen sulfide (H₂S) on airway inflammation induced by ozone (O₃) exposure and its mechanisms.METHODS: C57BL/6 mice (n=32) were randomly divided into control group, O₃ group, NaHS+O₃ group and NaHS group. The mice in O₃ group and O₃+NaHS group were exposed to 2.14 mg/m³ O₃ for 3 h on days 1, 3 and 5, while the mice in control group and NaHS group were exposed to filtered air. NaHS (14 μmol/kg) was administered intraperitoneally to the mice in NaHS group and O₃+NaHS group 30 min before each exposure. After the last exposure for 24 h, the airway responsiveness was determined, and bronchoalveolar lavage fluid (BALF) was collected for counting inflammatory cells and measuring total protein concentration. The lung tissues were collected for observing the morphological changes with HE staining. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), malondialdehyde (MDA) and NF-κB p65 protein in the lungs were determined.RESULTS: Compared with control group, the airway responsiveness, inflammatory cells, protein concentration, inflammation score, levels of IL-6, IL-8, MDA and NF-κB p65 in O₃ group increased significantly, but these in NaHS+O₃ group decreased compared with O₃  group.CONCLUSION: The present findings suggest that H₂S attenuates O₃ induced airway inflammation by inhibiting NF-κB expression and preventing lipid peroxidation.     

Effects of hydrogen sulfide on expression of urotensin II in acute asthmatic rats

AIM: To explore the effects of exogenously applied hydrogen sulfide (H₂S)on expression of urotensin II (U-II)in rats with ovalbumin-induced acute asthma. METHODS: Twenty-four male SD rats were randomly divided into control group, asthma group and NaHS treatment group (all n=8). At the 28th day after ovalbumin sensitization, the pulmonary function was measured. The pathological changes in the lung tissues were observed. The contents of U-II in plasma, lung tissues and bronchoalveolar lavage fluid (BALF)was also detected.RESULTS: The peak expiratory flow (PEF) was(6.5±0.1)L/s,(2.9±0.7)L/s and(5.7±0.5)L/s in control group, asthma group and NaHS treatment group, respectively. No statistical difference of the plasma U-II levels was observed among the three groups. In asthma group, the content of U-II in lung tissues was(43.8±2.0)ng/L and that in BALF was(58.0±12.3)ng/L, both of which were significantly higher than those in control group . In NaHS treatment group, the content of U-II in lung tissues was(14.0±1.9)ng/L and that in BALF was(20.2±6.7)ng/L, both of which were significantly lower than those in asthma grou p (F=337.68 and F=38.433, respectiuely, both P<0.01). The pathological score of the lung tissues in asthma group was 3(2-4), significantly higher than that in control group and NaHS treatment group . The positive correlations between the contents of U-II in lung tissues or BALF and the pathological scores were observed (r=0.746,r=0.714, respectively, both P<0.01). Significantly negative correlations between the contents of U-II in lung tissues or BALF and PEF were also found (r=-0.911 and r=-0.767, respectively, both P<0.01).CONCLUSION: U-II, a mediator acting via the way of paracrine or autocrine, may play a role in the pathogenesis of asthma in this animal model. The exogenous application of H₂S may play a regulatory role in asthma through inhibiting U-II to attenuate the inflammatory responses in asthma and exert protective effect on the pulmonary functions.     

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.