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1.
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.  相似文献   

2.
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.  相似文献   

3.
AIM: To investigate the role of the molar ratio of kaliuretic peptide/atrial natriuretic peptide in elderly essential hypertension(EH). METHODS: The levels of plasma kaliuretic peptide (KP) and atrial natriuretic peptide (ANP) in 46 elderly patients with essential hypertension (EH) and 11 spontaneuos hypertension rats (SHR) were determined by radioimmunoassay. Meanwhile, the concentation of KP and ANP in myocardium of rats were observed as well. RESULTS: Compared with control group, the plasma levels of KP and ANP in EH group were no significantly different, but the molar ratio of KP/ANP were lowered significantly (P<0.05). The levels of plasma KP and ANP in SHR were significantly higher than those in Wistar-Kyoto rats (WKY)(P<0.01 and P<0.05 respectively). However, the molar ratio of KP/ANP were markedly lower(P<0.01). The concentration of KP in atrium was significantly higher than that in ventricle in SHR(P<0.01). Moreover, there are no significantly different between SHR and SKY in atrium concentration of KP. CONCLUSION: KP and the molar ratio of KP/ANP maybe play an important role in pathogenesis of elderly essential hypertension.  相似文献   

4.
AIM: To investigate the correlation between microRNA-21 (miR-21) and pulmonary hypertension(PH) in the patients with heart failure with preserved ejection fraction (HFpEF). METHODS: From January 2014 to February 2016, 102 HFpEF patients presenting to Jiangxi Provincial People's Hospital were enrolled in this study. The patients were divided into PH-HFPEF group (n=36, PASP ≥ 50 mmHg) and HFpEF group (n=40, PASP<50 mmHg). Another 36 age-and sex-matched subjects served as healthy controls. The plasma level of miR-21 and its correlations with clinic data were examined, and multivariate logistic regression analysis was performed to identify the independent predictors of PH-HFpEF. Receiver operating characteristic (ROC) curve was analyzed, and the area under the curve (AUC) was calculated. The sensitivity and specificity for PH-HFPEF diagnosis were also determined. RESULTS: Age, plasma endothelin-1 (ET-1), interleukin-6 (IL-6), brain natriuretic peptide (BNP) and left atrial diameter (LAD) were significantly higher in PH-HFPEF group than those in HFPEF group (P<0.05). The level of miR-21 was significantly increased in PH-HFPEF group compared with HFpEF group and healthy control group. In addition, the miR-21 level was correlated with PASP (r=0.267, P=0.000), plasma IL-6 (r=0.302, P=0.013) and left ventricular mass index (LVMI) (r=0.515, P=0.036). Plasma IL-6 was positively correlated with plasma ET-1 (r=0.622, P=0.002). PASP was positively correlated with plasma IL-6 (r=0.36, P=0.023), ET-1 (r=0.76, P=0.004), BNP (r=0.43,P=0.031), and LAD (r=0.39, P=0.044). ROC curve showed that the AUC of miR-21 was 0.80. Multivariate logistic regression analysis showed that miR-21, LAD and BNP were the independent predictors of PH-HFpEF. CONCLUSION: Increased plasma miR-21 level is positively correlated to PH-HFpEF, and is an independent predictor of PH-HFpEF, suggesting that plasma miR-21 might be a useful new biomarker for predicting PH in HFpEF patients.  相似文献   

5.
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.  相似文献   

6.
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.  相似文献   

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AIM:To investigate Nrf2 that regulates the expression of γ-glutamylcysteine synthetase (γ-GCS) in the inflammatory cells in bronchial asthma guinea pig bronchoalveolar lavage fluid (BALF). METHODS:Adult male guinea pigs were randomly divided into control group (group A), asthmatic group (group B) and dexamethasone group (group C). Asthmatic model was established by the method of ovalbumin challenge. MDA concentration in the lung tissue homogenate was detected. The total cell count and the proportion of inflammatory cells in BALF were measured. The methods of immunohistochemistry and in situ hybridization were used for detection of the protein and mRNA expressions of Nrf2, Bach1 and γ-GCS. RESULTS:(1) The proportion of eosinophils (EOS) in BALF and the MDA concentration of the lung tissue in group B were higher than those in group A and group C. (2) The result of in situ hybridization indicated that the A value of γ-GCS was the highest in group A compared to group B and group C, but the A value of Nrf2 and Bach1 in 3 groups has no statistical significance. (3) Immunohistochemistry indicated that the A value of γ-GCS in group B was lower than that in group A. The positive rate in cell nucleus of Nrf2 in group B was lower than that in group A and group C. The positive rate in cell nucleus of Bach1 in group B was higher than that in group A and group C. (4) The mRNA expression of γ-GCS (A value) showed positive correlation with the positive rate in cell nucleus of Nrf2 and negative correlation with the positive rate in cell nucleus. A negative correlation between the proportion of EOS in BALF of group B and the γ-GCS mRNA was observed. CONCLUSION:There is disequilibrium between oxidation and anti-oxidation in bronchial asthma guinea pig. Inflammatory reaction decreases the expression of γ-GCS in the inflammatory cells in bronchial asthma guinea pig. Dexamethasone regulates the nuclear translocation of Nrf2/Bach1 and increases the expression of γ-GCS.  相似文献   

9.
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.  相似文献   

10.
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.  相似文献   

11.
AIM AND METHODS: To explore the effects calcitonin gene-related peptide (CGRP) and endothelin-1(ET-1) on the mechanisms of hypoxic pulmonary hypertension (HPH), the contents of CGRP and ET-1 in plasma of pulmonary artery and thoracic aorta and in extractives of lung and ventricular tissues of the chronic hypoxic rats were determined by radioimmunoassay. The changes of their hemodynamic indices and right heart hypertrophy index were monitored simultaneously. RESULTS: The level of pulmonary artery plasma CGRP was significantly higher than that of thoracic aorta plasma, but just the reverse was ET-1 or the ratio of ET-1 and CGRP in control rats( P<0.01). Compared with controls, the level of pulmonary artery plasma CGRP was gradually reduced in all hypoxic rats, but ET-1 was enhanced after 7 and 14 days of hypoxia and was decreased after 21 days of hypoxia. With prolonging time exposed to hypoxia, the level of thoracic aorta plasma CGRP was markedly increased in hypoxic animals compared with controls ( P<0.05), the positive correlation significantly with increased pulmonary arterial pressure( r = -0.896, P =0.05), but the lower level of thoracic aorta plasma ET-1 showed or negative correlation with pulmonary arterial pressure. CONCLUSIONS: These data suggest that the unbalance of effects of CGRP and ET may plays an important role in regulating the resistance of pulmonary circulation and has close relation with the formation of HPH.  相似文献   

12.
AIM: To study the effects of astragali radix extract (ARE) on renal resistance to atrial natriuretic peptide (ANP) in rats with experimental nephrotic syndrome. METHODS: Male Sprague-Dawley rats were randomly divided into normal control, adriamycin nephropathy (ADR), ADR treated with ARE (2.5 g· kg-1· d-1) and ADR treated with benazepril (10 mg· kg-1· d-1). After 6 weeks, rats received intravenous infusion of 2% body weight isotonic saline. Urinary cGMP excretion (UcGMPV), plasma ANP level, renal PDE5 activity and protein expression were also detected. RESULTS: ARE increased UNaV while ACEI was not natriuretic. Nephrotic rats had a blunted natriuretic response and reduced rate of UcGMPV after volume expansion despite higher plasma ANP concentration. ARE increased UcGMPV and restored partly natriuretic response to volume expansion. The activity and protein abundance of renal PDE5 were high in nephrotic rats. ARE significantly reduced the PDE5 activity and protein expression. CONCLUSION: ARE may ameliorate the renal resistance to ANP in rats with adriamycin nephropathy by inhibiting the PDE5.  相似文献   

13.
AIM: To investigate the effects of intensity of eosinophilic airway inflammation on cough response in guinea pigs sensitized and challenged with ovalbumin. METHODS: 34 sensitized guinea pigs were challenged with the aerosol of either saline (group A, n= 7) or 0.04% (group B, n= 7), 0.2% (group C, n= 8) and 1% (group D, n= 12) of ovalbumin. 24 hours later, cough response to inhaled capsaicin and airway responsiveness to inhaled methacholine (PC150) were measured. Total cell number and differentials in bronchoalveolar lavage were analyzed. RESULTS: After challenge, one animal in group C and five animals in group D died from severe wheezing. With ascending concentration of ovalbumin, cough frequency induced by inhaled capsaicin increased from (6±2) times/3 min in group A to (22±4) times/3 min in group D( P< 0.05). PC150, which did not change in group B, increased in both group C and group D significantly in addition to an increase in total cell number and eosinophils in bronchoalveolar lavage. Cough response to inhaled capsaicin was positively correlated with total cell number ( r= 0.84, P< 0.01) and eosinophils ( r= 0.78, P< 0.01) in bronchoalveolar lavage, and negatively correlated with PC150 ( r= -0.78, P< 0.01). There was a negative correlation between PC150 and total cell number ( r= -0.80, P< 0.01) or eosinophils ( r= -0.85, P< 0.01). CONCLUSION: Cough response in sensitized guinea pigs is enhanced and finally develops into wheezing with a progress in eosinophilic airway inflammation.  相似文献   

14.
AIM:To explore the expression of nuclear factor-κB(NF-κB)in asthmatic guinea pigs,and the effect of erigeron breviscapus,a protein kinase C(PKC)inhibitor,on the expression of nuclear factor-κB(NF-κB).METHODS:48 guinea pigs were randomly divided into 6 groups(n=8).Airway resistance and eosinophilic inflammation of airway wall were examined,the expression of NF-κB in the lung tissue was detected by immunohistochemical staining.RESULTS:The expression of NF-κB was mainly found in airway epithelium,all the asthmatic animals showed significantly higher optical densities than that of the normal control group(P<0.01),and the rats subjected therapeutic treatment for two weeks showed significantly lower NF-κB expression than those of the asthmatic groups(P<0.01).Positive correlation exist between the airway resistance and the percentage of cells expressing NF-κB in epithelium,and between the amount of eosinophil in airway wall and the percentage of cells expressing NF-κB in epithelium(P<0101).CONCLUSION:The increased expression of NF-κB in airway epithelium of the asthmatic guinea pigs suggested that NF-κB may be involved in asthma.And result that the increased expression of NF-κB was inhibited significantly by the treatment of the erigeron breviscapus suggested that PKC may play a significant role in the pathogenesis of asthma through NF-κB.  相似文献   

15.
AIM:To study the changes of plasma atrial natriuretic peptide(ANP), endothelin-1 (ET-1) and serum cardiac troponin I(cTnI) levels and the effects of ANP and ET-1 on myocardium in crush injury rats.METHODS:Crush injury was produced in SD rats,the serum levels of cardiac enzyme and cardiac troponin I,plasma levels of ANP and ET-1 were studied by automated biochemical analyzer,automated chemiluminescence assay and radioimmunoassay. RESULTS:The plasma ET-1 level was much lower,the levels of plasma ANP and serum cardiac enzyme and cTnI were much higher after crush injury than those of the control group(P<0.05).CONCLUSION:ANP and ET-1 may play an important role in cardiomyocyte injury in the early stage of crush injury.  相似文献   

16.
AIM: To evaluate the relationship between endothelin-1 (ET-1)/nitric oxide (NO) and hearing impairment in type 2 diabetes mellitus (DM).METHODS: Eighty-eight type 2 diabetic patients with no signs of microangiopathy (retinopathy and nephropathy) or peripheral neuropathy, and 53 healthy subjects in the same period were enrolled in this study. Auditory function was evaluated using pure tone audiometry. Totally,type 2 DM group (n=88) and normal control group (NC, n=53) were divided into subgroups based on the presence and absence of hearing impairment. The concentration of plasma ET-1 was detected by radioimmunoassay. The concentration of serum NO was measured by the method of nitric acid reductase.RESULTS: Significantly increased plasma ET-1 and decreased serum NO were observed in diabetic patients with hearing impairment compared with those in diabetic patients without hearing impairment. The results of multivariate logistic regression analysis showed that hearing impairment in type 2 DM group was significantly associated with elevated level of HbA1c (OR=4.525, P<0.05), LDL-C (OR=2.381,P<0.05) and plasma ET-1 (OR=6.207,P<0.01). Besides, elevated serum level of NO (OR=0.862, P<0.05) was associated with lower risk of hearing impairment in diabetics.CONCLUSION: Hearing impairment may happen earlier than other complications in diabetic patients. In addition to hyperglycemia and hyperlipemia, high level of ET-1 and low levels of NO might contribute to hearing impairment in diabetic patients.  相似文献   

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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.  相似文献   

20.
AIM:To examine the changes and clinical implications of the plasma atrial natriuretic peptide (ANP), brain natriuretic peptide(BNP) and C-type natriuretic peptide(CNP) levels in type 2 diabetic patients with vascular complications. METHODS:9 subjects without diabetes, 34 diabetic patients without vascular complications and 23 diabetic patients with vascular complications were enrolled in the study and categorized into three groups. Plasma proANP, BNP fragment and N-terminal pro-CNP (NT-proCNP) were measured by enzyme linked immunosorbent assay (ELISA). The changes and associations of the plasma natriuretic peptide levels among three groups were analyzed. RESULTS:Compared with those in the controls and diabetics without vascular complications, the plasma proANP and BNP fragment levels in diabetic patients with vascular complications increased significantly (P<0.01). However, the plasma NT-proCNP level in this group decreased significantly (P<0.01). Nevertheless, no significant differences in the plasma proANP, BNP fragment and NT-proCNP levels among three subgroups (diabetics patients with macrovascular and/or microvascular complications) were observed (P>0.05). The plasma ANP level of diabetic patients with vascular complications was corelated significantly with the BNP levels (r=0.309, P<0.05). Furthermore, the ANP and BNP levels were correlated significantly with the CNP level (r=-0.374, P<0.05; r=-0.653, P<0.01). CONCLUSION:Measurement of the plasma ANP, BNP and CNP levels together may be a simple, cost-effective and reliable way to screen for diabetic patients with vascular complications.  相似文献   

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