Allergens-induced sensitization alters airway epithelial adhesion molecules expression in mice / 生理学报

To explore the relationship between the epithelial adhesion molecules and immune responses of airway epithelium, we observed the expression of integrin β4 and intercellular adhesion molecule-1 (ICAM-1) in the mice airway epithelium after sensitization with allergens. BALB/c mice were sensitized with intraperitoneal injection of ovalbumin (OVA) or house dust mite (HDM) and then developed airway hyper-responsiveness as determined by barometric whole-body plethysmography. Both OVA and HDM sensitization led to increases of the number of peripheral leukocytes as well as inflammatory cells infiltration in lungs. OVA sensitized mice showed more severe inflammatory cells infiltration than HDM sensitized mice. Immunohistochemistry analysis of mice lung tissues revealed that sensitization with both allergens also led to a decrease of integrin β4 expression and an increase of ICAM-1 expression in airway epithelia. OVA sensitized mice showed a more significant increase of ICAM-1 expression compared with HDM sensitized mice. siRNA mediated silencing of integrin β4 gene in 16HBE cells resulted in an up-regulation of ICAM-1 expression. Our results indicate a possible role of airway epithelial adhesion molecules in allergen-induced airway immune responses.

Effects of feixin decoction on the contents of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in the rat model of hypoxic pulmonary hypertension / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of Feixin Decoction (FXD) on the hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in the rat model of hypoxic pulmonary hypertension (HPH), and to study its mechanisms for treating HPH.</p><p><b>METHODS</b>Forty healthy male SD rats were randomly divided into four groups, i. e., the normal control group, the HPH model group, the FXD group, and the Nifedipine group, 10 rats in each group. The HPH rat model was prepared using normal pressure intermittent hypoxia method. Except the normal control group, rats in the rest groups were fed in a self-made hypoxic plexiglass cabin, with the poor oxygen condition for 8 h daily for 14 successive days. Then the distilled water (at 30 mL/kg) was given by gastrogavage to rats in the normal control group and the HPH model group. FXD (at 28 g/kg) and Nifedipine (at 20 mg/kg) were given by gastrogavage to rats in the FXD group and the Nifedipine group respectively, once daily, for 14 successive days. Besides, hypoxia was continued for 14 days while medicating. The mean pulmonary artery pressure (mPAP) was detected on the second day after the last medication. The morphology of the pulmonary arteriole was detected. The ratio of pulmonary artery wall area and tube area (WA%) was determined. The protein and mRNA expressions of HIF-1alpha and VEGF were detected using immunohistochemistry and in situ hybridization technique.</p><p><b>RESULTS</b>Compared with the normal control group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly increased in the model group (P < 0.01, P < 0.05). Compared with the HPH model group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly decreased in the FXD group (P < 0.01, P < 0.05).</p><p><b>CONCLUSIONS</b>FXD down-regulated the expression of VEGF through decreasing the expression of HIF-1alpha. One of its mechanisms for treating HPH might be partially due to reversing the remodeling of pulmonary vascular smooth muscle.</p>

The expression and possible role of SENP1 in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the dynamic expression and role of SENP1 (SUMO-specific proteases-1) in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension (HPH).</p><p><b>METHODS</b>Forty adult male Wistar rats were randomly divided into 5 groups (n = 8), and exposed to normoxia (Control group) or exposed to hypoxia for 3, 7, 14 or 21 d, respectively. The HPH models were established by normobaric intermittent hypoxia. Mean pulmonary arterial pressure (mPAP), right ventricle hypertrophy index (RVHI), and vessel morphometry were measured. Reverse transcriptase-polymerase chain reaction(RT-PCR) and in situ hybridization were used to determine the mRNA expression of SENP1. Immunohistochemistry and Western blot were used to determine the protein expression of SENP1.</p><p><b>RESULTS</b>The hypoxic rats developed pulmonary vascular remodeling in pulmonary arterioles after 7 d of hypoxia exposure. Pulmonary vascular remodeling in pulmonary arterioles significantly increased after 14 d of hypoxia. The level of mPAP in hypoxic rats increased significantly after 7 d of hypoxia, reached its peak after 14 d of hypoxic exposure. RVHI was markedly increased after 14 d of hypoxia. In situ hybridization and immunohistochemical analysis showed that SENP1 mRNA and protein were positively stained in control. SENP1 mRNA expression had little changes after exposure to hypoxia compared with the control, however, SENP1 protein expression was declined gradually after 7 d of hypoxia. The results of RT-PCR and Western blot showed that the same dynamic expression of SENP1 mRNA and protein in lung tissues of rats. Linear correlation analysis showed that SENP1 protein were negatively correlated with mPAP, pulmonary vascular remodeling index and RVHI.</p><p><b>CONCLUSION</b>Under chronic hypoxia, SENP1 protein can be degradated. The dynamic expression of SENP1 protein may play a role in implicating in the development of HPH.</p>

The effect of transcription factor KLF2 in expression of gamma-GCS depend on regulation by Nrf2 in lung of rats with chronic obstructive pulmonary disease / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the expression of lung Krüppel-like transcription factor (KLF2/LKLF) in lung tissues of rats with chronic obstructive pulmonary disease (COPD) and the relationship between KLF2 and NF-E2-related factor 2 (Nrf2), and make further explore the effects of KLF2 on the expression of gamma-glutamylcysteine synthetase (gamma-GCS).</p><p><b>METHODS</b>Twenty-two male SD rats were randomly divided into a COPD group (n = 10) and a normal control group (n = 11). The rat model of COPD established by cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS), and lung tissues were obtained. The expressions of KLF2, Nrf2, gamma-GCS mRNA and protein in lung tissues were measured by immunohistochemistry (IHC), Western blot, in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR). To explore the relationship between KLF2 and Nrf2 protein,we utilize the method of co-immunoprecipitation (CO-IP).</p><p><b>RESULTS</b>IHC and Western blot showed that protein expressions of KLF2, Nrf2, gamma-GCS were higher in the lung tissues from rats with COPD than those in the control groups (all P < 0.05). The levels of KLF2, gamma-GCS mRNA were markedly increased in the COPD group (all P < 0.01) while Nrf2 mRNA expression in COPD group had no significant difference with that in control group ( P > 0.05). CO-IP result showed that KLF2 were obviously present in immunoprecipitates of Nrf2 (P < 0.01) . Linear correlation analysis showed that the level of KLF2 protein was positively correlated with the level of Nrf2 protein (P < 0.05), and KLF2, Nrf2 proteins were positively correlated with gamma-GCS mRNA and protein (all P < 0.05).</p><p><b>CONCLUSION</b>The expression of KLF2 is significantly up-regulated in COPD, which maybe up-regulate gamma-GCS mRNA expression by increasing Nrf2 expression and nuclear translocation against oxidative stress.</p>

The expression of hypoxia-inducible factor-1alpha and its hydroxylases in pulmonary arteries of patient with chronic obstructive pulmonary disease / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the expression of hypoxia-inducible factor-lalpha subunit (HIF-1alpha), HIF prolyl hydroxylase domain-containing protein(PHDs) and factor inhibiting HIF-1(FIH) in pulmonary arteries of patient with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Pulmonary specimens were obtained from patients undergoing lobectomy for lung cancer, 12 had concurrent COPD (COPD group) and 14 without COPD (control group). The ratio of vascular wall area to total vascular area (WA%) and pulmonary artery media thickness (PAMT) was observed, and HIF-1alpha and its hydroxylases(PHD1, PHD2, PHD3, FIH) mRNA and protein were detected by in situ hybridization and immunohistochemistry respectively.</p><p><b>RESULTS</b>WA% and PAMT of COPD patients(50 microm +/- 9 microm, 40% +/- 5%, were statistically different from those of the control subjects (39 microm +/- 6 microm, 31% +/- 4%, P < 0.01). Relative quantification of mRNA and protein levels (absorbance, A) showed that HIF-lalpha mRNA and protein levels in COPD group (0.230 +/- 0.036,0.275 +/- 0.039) were statistically higher than those of the control subjects (0.174 +/- 0.029, 0.102 +/- 0.015, P < 0.01 ), and that the protein level increased more markedly. PHD1 mRNA in COPD subjects (0.180 +/- 0.030) was comparable to that in control group (0.191 +/- 0.029, P > 0.05); PHD2 and PHD3 mRNA levels in COPD (0.245 +/- 0.044, 0.252 +/- 0.023) were significantly higher than those in control group(0.182 +/- 0.028, 0.127 +/- 0.017, P < 0.01). On the other hand, in COPD subjects PHD1 protein (0.104 +/- 0.015) was significantly lower(P < 0.01), whereas PHD2 protein (0.274 +/- 0.044) was significantly higher(P < 0.01) than those in control group(0.209 +/- 0.023, 0.219+/- 0.043). As for PHD3 protein, no significant changes were observed between the two groups (0.161+/- 0.023 in COPD, 0.146 +/- 0.021 in control, P > 0.05). FIH mRNA and protein both showed no differences between the two groups. Linear correlation analysis showed that HIF1alpha protein was positively correlated with WA%, PAMT, PHD2 mRNA and protein, PHD3 mRNA, and that HIF1alpha protein was negatively correlated with PHD1 protein.</p><p><b>CONCLUSION</b>PHDs may be involved in the process of hypoxic pulmonary vascular remodeling in COPD via regulation of HIF-1alpha gene expression</p>

The pathway of PI3k/Akt-aPKCiota/zeta-Nrf2 regulating the expression of gamma-glutamylcysteine synthetase in the bronchial epithelial cells of rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effect of the signal pathway of phosphoinositol-3-kinase (PI3K)/Akt-antypical protein kinase C(iotazeta) (aPKC(iotazeta))-Nuclear factor-E2 related factor (Nrf2) on gamma-glutamylcysteine synthetase (gamma-GCS) of the bronchial epithelial cells of rats after exposure to cigarette smoke extracts (CSE).</p><p><b>METHODS</b>gamma-GCS, Nrf2, p-Akt and p-aPKC(iotazeta) proteins were semi-quantified by Western blot. gamma-GCS protein expression was assessed by immunocytochemistry. gamma-GCS mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). Nrf2 protein was observed by immunofluorescence. The rate of the cells expressed p-Akt were analyzed by flow cytometry. GSH content and gamma-GCS activity were measured.</p><p><b>RESULTS</b>GSH content, Nrf2 protein of nucleus, p-aPKC(iotazeta) protein, p-Akt protein and positive cells, gamma-GCS protein and mRNA and activity were significantly increased after exposure to CSE for 3 hours. aPK(iotazeta) inhibitor RO813220 significantly reduced the expression of p-aPKC(iotazeta) protein, gamma-GCS protein and mRNA and activity, but enhanced Nrf2 protein of cytoplasm expression, had no effect on p-Akt. p-Akt inhibitor LY294002 and RO813220 + LY294002 decreased p-aPKC(iotazeta) protein, p-Akt protein and positive cells, gamma-GCS protein and mRNA and activity expression, increased Nrf2 protein of cytoplasm expression. The correlation analysises demonstrated that there were a positive correlation between Nrf2 and gamma-GCS, p-Akt, p-aPKC(iotazeta), between p-Akt and Nrf2, p-aPKC(iotazeta), gamma-GCS, between p-aPKC(iotazeta) and Nrf2, p-Akt, gamma-GCS.</p><p><b>CONCLUSION</b>CSE might upregulate gamma-GCS expression through PI3K/Akt-aPKC(iotazeta)-Nrf2 signaling pathway in the bronchial epithelial cells of rats.</p>

The roles of PPAR-gamma/PGC-1alpha to Nrf2/gamma-GCS-h in lung of guinea pigs with bronchial asthma / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h in lung of guinea pigs with bronchial asthma, and to explore the roles of them.</p><p><b>METHODS</b>Forty adult male guinea pigs were randomly divided into 4 groups: the control group (group A), asthmatic group ( group B), dexamethasone group (group C) and rogridone group (group D), 10 guinea pigs in each group. The asthmatic model was established by the ovalbumin challenge method. Expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h mRNA in lung tissue were assayed by in situ hybridization. Expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h protein were detected by immunohischemistry and by Western blot.</p><p><b>RESULTS</b>In situ hybridization showed that the expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h mRNA in lung tissue were the lowest in group B and the comparison among groups showed statistical significant (all P < 0.01). Immunohistochemistry and Western blot indicated that the value of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h protein in lung tissue were the lowest in group B, and expressed primarily in nucleus, the differences being statistically significant (all P < 0.01). There was positive correlation between PPAR-gamma and PGC-1. gamma-GCS-h mRNA also positively correlated between PPAR-gamma/PGC-1alpha and Nrf2 in nucleus, and the expression of Nrf2 was also positively correlated with PPAR-gamma/ PGC-1alpha.</p><p><b>CONCLUSION</b>In acute asthmatic models induced by ovalbumin, the expressions of PPAR-alpha/PGC-1alpha and Nrf2/gamma-GCS-h were decreased, and PPARgamma/PGC-1alpha could up-regulate the expressions of Nrf2/gamma-GCS-h to increase the antioxidant defense of tissues, thus being implicated that PPARgamma/PGC-1alpha might play important roles in the pathogenesis and prevention of asthma.</p>

The cooperation of OS-9 and PHDs in hypoxia-induced pulmonary hypertension of rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the dynamic expression of hypoxia-inducible factor 1alpha, PHDs and OS-9 in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.</p><p><b>METHODS</b>SD rats were randomly divided into 5 groups (n = 8) and exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively. RT-PCR and in situ hybridization were used to determine the expression of mRNA. Immunohistochemistry and Western blot were used to determine the expression of protein.</p><p><b>RESULTS</b>HIF-1alpha protein was poorly positive in control, markedly up-regulated after 3 d and 7 d of hypoxia (P < 0.05, vs group C), and then declined slightly after 14 d and 21 d of hypoxia. HIF-1alpha mRNA increased dramatically after 14 d of hypoxia (P < 0.05, vs group C). PHD1, PHD2 mRNA and protein was positive in group C. PHD2 mRNA and protein were up-regulated after 3 d of hypoxia (P < 0.05, vs group C), reaching its peak after 14 d of hypoxia while PHD1 protein declined after 14 d of hypoxia (P < 0.05, vs group C) without statistic mRNA changing. PHD3 mRNA and protein were detected at low level in control, markedly up-regulated after 3 d of hypoxia (P < 0.05, vs group C), and then PHD3 mRNA kept at high level while PHD3 protein declined after 14 d of hypoxia (P < 0.05, vs 7 d). OS-9 mRNA was positively in control, markedly decreased after 3 d of hypoxia (P < 0.05, vs group C), reaching its lowest lever after 14 d of hypoxia. Linear correlation analysis showed that OS-9 protein was positively correlated with OS-9 mRNA (r = 0.82, P < 0.01) and HIF-1alpha protein (r = 0.57, P < 0.01).</p><p><b>CONCLUSION</b>HIF-1alpha, PHDs and OS-9 are all involved in the pathogenesis of hypoxic pulmonary hypertension in rats. OS-9 may interact with both HIF-1alpha and PHDs to promote PHD-mediated hydroxylation of HIF-1alpha.</p>

The preventative effects of protein tyrosine kinase on the inflammation and airway remondeling in lung of guinea pigs with bronchial asthma / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of protein tyrosine kinase on the inflammation and airway remodeling in lung of guinea pigs with bronchial asthma.</p><p><b>METHODS</b>30 adult male guinea pigs were randomly divided into 3 groups (n=3): control group (C group), asthmatic group(A group)and genistein group (B group). Asthmatic model was established by ovalbumin intraperitoneal injection and ovalbumin inhalation. The total cell and the proportion of inflammatory cell in bronchial alveolar lavage fluid(BALF), inflammatory cell infiltration and index of remodeling of bronchiole were measured, respectively. The expression of p-tyrosine in lung tissue was examined by immunohistochemistry.</p><p><b>RESULTS</b>The total cell and proportion of eosinophil in BALF of A group were significantly higher than that of C group (P < 0.01), but compared with A group, the total cell and proportion of eosinophil in BALF of B group were much lower (P < 0.01). The number of eosinophile and lymphocyte of bronchiole in A group were significantly higher than that of C group (P < 0.01), but compared with A group, the number of eosinophile and lymphocyte in bronchiole of B group were much lower (P < 0.01). Compared with A group, the remodeling of bronchiole of B group was significantly relieved (P <0.01), there was no difference between B and C group (P > 0.05). Immunohistochemistry indicated that in A group the p-tyrosine was more positively expressed at the bronchial smooth muscle, bronchial epithelium, smooth muscle of vessel and inflammatory cell, especially at smooth muscle of bronchi and vessel and inflammatory cell than that of C group (P <0.01), there was no difference between B group and C group (P > 0.05).</p><p><b>CONCLUSION</b>PTK played a key role in inflammation and bronchial remodeling in lung of guinea pigs with bronchial asthma. The Protein tyrosine kinase inhibitor genistein could prevent and inhibit the inflammation and bronchial remodeling in lung of guinea pigs with bronchial asthma.</p>

Roles of NRF2 regulating gamma-glutamylcysteine synthetase in lung of rats with chronic obstructive pulmonary disease / 中国应用生理学杂志

<p><b>AIM</b>To investigate the expression and relationship of gamma-glutamylcysteine synthetase (gamma-GCS) and NF-E2-related factor2 (NRR2) in lung of rat with chronic obstructive pulmonary disease (COPD)in order to elucidate the possible important role of gamma-GCS and NRF2 in pathogenesis of COPD.</p><p><b>METHODS</b>The rat COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposed to cigarette smoke daily. The gamma-GCS activity was measured, the expression of gamma-GCS mRNA in lung was examined by in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR), the protein expressions of NRF2, gamma-GCS in lung were detected by immunohistochemical (IH) and Western blot respectively.</p><p><b>RESULTS</b>The gamma-GCS activity was higher in COPD group than that in control group. The expressions of gamma-GCS mRNA in COPD group was stronger than those in control group. ISH showed that the gamma-GCS mRNA was expressed in alveolar epithelium and bronchial smooth muscle cell in COPD. The protein expressions of NRF2, gamma-GCS were significantly higher than the control group. IH showed that NRF2, gamma-GCS proteins were expressed in alveolar and bronchial epithelium in the COPD group. There was a positive correlation between NRF2 and gamma-GCS and gamma-GCS mRNA.</p><p><b>CONCLUSION</b>NRF2 may play an important role in the mechanism of COPD oxidative stress vis up-regulation of gamma-GCS.</p>

Effects of Nrf2 on gamma-glutamylcysteine synthase in lung of guinea pigs with bronchial asthma / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of Nrf2 (Nuclear-E2 related factor) on gamma-glutamylcysteine synthase (gamma-GCS) in lung of guinea pigs with bronchial asthma.</p><p><b>METHODS</b>20 adult male guinea pigs were randomly divided into two groups (n = 10): control group (C group) and asthmatic group (A group), asthmatic model was established by ovalbumin intraperitoneal and ovalbumin inhalation. The reactive oxygen piece (ROS), reduced glutathione (GSH), oxidant glutathione (GSSG) and total GSH in lung tissue were examined respectively. Inflammatory cell infiltration and index of remodeling of bronchiole were detected. In situ hybridization detected the gamma-GCS heavy subunit (gamma-GCS h) mRNA in lung tissue. Immunohistochemistry detected the expression of Nrf2 protein and gamma-GCS protein in lung tissue. RT-PCR measured the expression of Nrf2 mRNA in lung tissue. The activity of gamma-GCS was measured by coupled enzyme assay.</p><p><b>RESULTS</b>(1) The number of eosinophils and lymphocytes in bronchiole of A group were significantly higher than that of C group (P < 0.05), the remodeling of bronchiole in A group was definite. (2) ROS (U/mg pro), GSSG (micromol/g pro) and total GSH in lung tissue of A group were significantly higher than that of C group (P < 0.01). The GSH/GSSG in lung tissue of A group was much lower than that of C group (P < 0.01), GSH in lung tissue showed no difference between A group and C group. (3) Immunohistochemistry indicated that Nrf2 protein and gamma-GCS protein were more positively expressed in A group than that in C group (P < 0.01). In situ hybridization discovered that the expression of gamma-GCS-h mRNA in lung tissue of A group was more positive than that of C group. (4) RT-PCR showed that the expression of Nrf2 mRNA was no difference between A group and C group (P > 0.05). (5) The activity of gamma-GCS of A group was (28 +/- 8)U which was significantly higher than that of C group (9 +/- 2)U (P < 0.01). (6) Linear correlation analysis indicated that in lung tissue of guinea pig with asthma there existed strongly positive relationship among ROS, GSSG and the expression of Nrf2, gamma-GCS mRNA, gamma-GCS protein, the activity of gamma-GCS, there existed strongly negative relationship among GSH/GSSG and the expression of Nrf2, gamma-GCS mRNA, gamma-GCS protein, the activity of gamma-GCS.</p><p><b>CONCLUSION</b>There existed oxidative stress in lung of guinea pigs with bronchial asthma, which possibly positively regulated gamma-GCS via up regulating transcription factor Nrf2.</p>

Effects of adrenomedullin regulating inducible nitric oxide synthase on proliferation and apoptosis in hypoxic pulmonary artery smooth muscle cells / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of hypoxia on the proliferation and apoptosis of PASMC, to evaluate the role of iNOS protein expression and ADM on the hypoxic pulmonary hypertension (HPH) pathogenesis.</p><p><b>METHODS</b>To culture rat pulmonary artery smooth muscle cell (PASMC), cultured PASMC cells were grouped into: normoxic group; hypoxic group; hypoxia + L-NAME group; hypoxia+ ADM group. Proliferation of PASMC were investigated by MTT and PCNA. Apoptosis of PASMC were examined by flow-cytometry. Westen blot was used to measure protein expression of iNOS induced by hypoxia.</p><p><b>RESULTS</b>(By MTT, the value of 24 h hypoxia was significantly higher than that in the normoxic group (P < 0.01), the value of the hypoxia + ADM was significantly lower than that in hypoxia group, the value of the hypoxia + L-NAME was significantly higher than those of hypoxic group and normoxic group (P < 0.01). (2) By immunohistochemistry, PCNA was poorly positive in PASMC, whereas positive after 24 h hypoxia (P < 0.01), ADM inhibited the expression of PCNA significantly (P < 0.01), whereas L-NAME increased the expression of PCNA significantly (P < 0.01). (3) By FCM, apoptosis index was not significantly different between the normoxic group, hypoxic group, hypoxia + L-NAME and hypoxia + ADM (P > 0.05). (4) By Western blot, iNOS expression was poorly positive in control group, positive after 4 h hypoxia (P < 0.01), increasing as the hypoxia environment continued (P < 0.01). L-NAME had no effect on iNOS protein, ADM promoted iNOS expression (P < 0.01).</p><p><b>CONCLUSION</b>(1) Hypoxia stimulates the proliferation of PASMC, and has no obvious effects on the apoptosis of PASMC. (2) Hypoxia induces the expression of iNOS, ADM can increase expression of iNOS, ADM and INOS plays a role of protection in HPH pathogenesis.</p>

Location and expression of NF-kappaB in lung of rats with chronic obstructive pulmonary disease / 中国应用生理学杂志

<p><b>AIM</b>To elucidate the location and effects of transcription factor-nuclear factor-kappaB (NF-kappaB) in lung tissues of rats with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Fourteen male Wistar rats were randomly divided into COPD model and control groups equally. The COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposure to cigarette smoke daily. We detected the NF-kappaB p65 protein in lung by immunohistochemical method, and the expression of NF-kappaB p65 mRNA in lung by in situ hybridization.</p><p><b>RESULTS</b>Immunohistochemistry, the expression of NF-kappaB p65 protein in alveolar, bronchiolar epithelium and arteriolar endothelium was significantly higher in the COPD group (0.426 +/- 0.007, 0.434 +/- 0.012 and 0.313 +/- 0.007, respectively) than those of the control group (0.115 +/- 0.006, 0.116 +/- 0.005 and 0.095 +/- 0.007, respectively, all P < 0.01). In situ hybridization showed that the expressions of NF-kappaB p65 mRNA in alveolar epithelium (0.203 +/- 0.008), bronchiolar and arteriolar smooth muscle cell (0.208 + 0. 010 and 0.206 + 0.007) of rats in the COPD group were stronger than those in the control group (0.100 +/- 0.006, 0.102 +/- 0.002 and 0.103 +/- 0.003 respectively) by semiquantitative analysis (all P < 0.01).</p><p><b>CONCLUSION</b>The expression and nuclear translocation of NF-kappaB may be the basis event of gene expression of many cytokines and inflammatory mediators, which may positively regulate gene expression of many cytokines and inflammatory mediators in various cell lines.</p>

Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypoxia-inducible factor-1alpha (HIF-1alpha) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1alpha, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1alpha and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension.</p><p><b>METHODS</b>Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry.</p><p><b>RESULTS</b>mPAP values were significantly higher than the control values after 7days of hypoxia [(18.4 +/- 0.4) mmHg, P < 0.05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1alpha protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1alpha protein was markedly increased by day 3 (0.20 +/- 0.02, P < 0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1alpha mRNA increased significantly after day 14 of hypoxia (0.20 +/- 0.02, P < 0.05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15 +/- 0.02, P < 0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1alpha mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1alpha mRNA was positively correlated with VEGF mRNA and protein (P < 0.01).</p><p><b>CONCLUSION</b>HIF-1alpha and VEGF are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats.</p>

Change of the expression of adrenomedullin in lung and effect on contraction of isolated tracheal strip of asthmatic guinea pigs / 中国应用生理学杂志

<p><b>AIM</b>To study the formation and localization of ADM mRNA in lung tissues and investigate the effects of ADM on isolated tracheal strip contraction induced by histamine in asthmatic guinea pig.</p><p><b>METHODS</b>The guinea pigs (n = 22) were randomly divided into two groups of 11 each: asthmatic group and control group. The formation and localization of ADM mRMA were observed by in site hybridization. The effect of exogenous ADM on contractions of isolated tracheal strip of the asthmatic guinea pigs to histamine was examined.</p><p><b>RESULTS</b>There were strong positive expression for ADM mRNA in airway epithelial cells (AEC), smooth muscle cells (ASMC) in asthmatic group. The control group showed significantly decreased number of ADM mRNA positive cells in lung tissues. From 10(-11) mol/L to 10(-7) mol/L, ADM may cause concentration depend pentiation of the isolated tracheal strip contraction induced by histamine of asthmatic group which was higher significantly compared the control group (P < 0.05). 10(-8) mol/L ADM reached the maximal relaxation, with the increasing of ADM, neither asthmatic nor control group can increase the relaxation.</p><p><b>CONCLUSION</b>There is ADM mRNA overproduction in AEC and ASMC and exogenous ADM may inhibit isolated tracheal strip contraction induced by histamine of asthmatic guinea pig, which may contribute to airway inflammation and hyperresponsiveness in asthma.</p>