Baicalin inhibits PDGF-induced proliferation and migration of airway smooth muscle cells.

Airway smooth muscle (ASM) cell proliferation and migration play important roles in airway remodeling in asthma. In vitro platelet-derived growth factor (PDGF) induced ASM cell proliferation and migration. Baicalin is one of flavonoid extracts from Scutellaria baicalensis, which has an anti-asthma effect. However, little is known about its role in PDGF-induced proliferation and migration in rat ASM (RASM) cells. In this study, we aimed to investigate the effects of baicalin on PDGF-induced RASM cell proliferation and migration. We also identified the signaling pathway by which baicalin influences RASM cell proliferation and migration. In the current study, we demonstrated that baicalin suppressed PDGF-induced RASM cell proliferation, arrested PDGF-induced cell-cycle progression. It also suppressed PDGF-induced RASM cell migration. Furthermore, baicalin suppressed PDGF-induced expression of phosphorylated p38, ERK1/2 and JNK in RASM cells. In summary, our study is the first to show that baicalin pretreatment can significantly inhibit PDGF-induced RASM cell proliferation and migration by suppressing the MAPK signaling pathway, and baicalin may be a useful chemotherapeutic agent for asthma.

[Changes of ophthalmic blood flow in obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To observe the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) blood flow and the changes of eye vascular auto-regulation in patients with obstructive sleep apnea-hypopnea syndrome (OSAS). METHODS: It was a case-control study. Fifteen health overweight male adult (as normal control) and 42 patients with OSAS were randomly selected from examination center and sleep detection center, respectively. The OSAS patients were divided into mild (14 patients) and moderate and severe (28 patients) groups based on the apnea-hypopnea index (AHI). All subjects filled the sleep questionnaire and carried out polysomnogram monitoring all night for at least 7 hours. Fasting peripheral venous blood was collected at 7 AM on next day. The end-tidal CO(2) (ETCO(2)), intraocular pressure and color doppler sonography were examined next day to record the data in the inspection process before and after Mueller maneuver. Doppler ultrasound measurement of ocular blood flow diameter and blood flow velocity values were described in the median (max, min) and compared with Kruskal-Wallis test. And then two groups were compared with Bonferroni t test. Ocular blood flow velocity of patients with OSAS and PSG monitoring indicators were analyzed using partial correlation analysis. RESULTS: OA inner diameter in moderate and severe OSAS group [0.08 (0.15, 0.06) cm] was lower than that in healthy control [0.15 (0.26, 0.11) cm] and the difference was statistically significant (P = 0.000). PCA inner diameter in moderate and severe OSAS group [0.10 (0.13, 0.07) cm] were higher than that in healthy controls [0.05 (0.09, 0.04) cm]. CRA peak systolic velocity (PSV) in moderate and severe OSAS group [16.50 (19.40, 13.10) cm/s] was greater than that in healthy controls [11.30 (16.70, 8.20) cm/s]. The differences between these two groups were statistically significant (PCA inner diameter: P = 0.000, CRA-PSV: P = 0.001). The difference of CRA end diastolic velocity (EDV) between the moderate and severe group [8.90 (9.90, 5.10) cm/s], mild group [7.00 (8.30, 4.50) cm/s] and healthy control group [5.50 (7.40, 3.40) cm/s] was statistically significant (χ(2) = 14.45, P < 0.05). PCA-PSV [32.50 (43.10, 19.10) cm/s] and PCA-EDV [12.80 (15.20, 5.70) cm/s] in the moderate and severe group were higher than those in healthy control group [22.60 (32.20, 12.40) cm/s] and [7.20 (11.20, 3.90) cm/s], as well as those in the mild group [24.00 (30.70, 13.30) cm/s] and [8.00 (9.90, 3.90) cm/s]. These differences were statistically significant (PCA-PSV: P = 0.000, 0.002; PCA-EDV: P = 0.000, 0.001). The diameter of OA and PCA correlated negatively with ETCO(2) (r = -0.41, -0.34; P < 0.05); CRA-PSV was correlated with SaO2 min (r = -0.37, P < 0.05). CRA-EDV was correlated with ETCO(2) and SaO2 mean (r = 0.57, -0.39; P < 0.05). PCA-PSV was correlated with SaO2 min and MAI (r = -0.34, 0.56; P < 0.05). PCA-EDV was correlated SaO2 min and MAI (r = -0.29, 0.61; P < 0.05). CONCLUSIONS: The diameter and blood flow of OA, PCA and CRA change in OSAS patients. Compared with non-OSAS patients, the autoregulation function of PCA and CRA is weakened in OSAS patients.

Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression.

BACKGROUND: The signal transducer and activator of transcription 6 (STAT6) expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 (Th2) cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore, antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation. METHODS: In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide (ASODN) overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA (pANTI-STAT6), then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma. RESULTS: In vitro, we showed suppression of STAT6 expression and interleukin (IL)-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate (FITC)-labeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production. CONCLUSION: These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.

[The association between polymorphism of beta(1)-adrenoceptor genes and cardiovascular complication in obstructive sleep apnea-hypopnea syndrome patients in Han population].

OBJECTIVE: To investigate the association between polymorphism of beta(1)-adrenoceptor genes and cardiovascular complication in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. METHOD: The Gly389Arg polymorphism of beta(1)-adrenoceptor genes was identified by polymerase chain reaction-restricted fragment length polymorphism assay in 192 OSAHS patients of "Han" population of China. The effect of polymorphisms in the OSAHS group on parameters of polysomnography and cardiovascular complication was analyzed. Analysis of variance, t test and chi-square test were used for statistics. RESULT: The distributions with CC genotype were significantly higher than those with CG/GG genotype. The frequencies with C allele were significantly higher than those with G allele. The OSAHS patients with CC genotype had higher percentage of time of oxygen saturation lower than 90% (T90) and longer apnea time (Tmax) than those with CG/GG genotype. The lowest saturation of blood oxygen (minSaO2) in patients with CC genotype was significantly lower than that in patients with CG/GG genotype. Cardiovascular diseases (P < 0.05) except sinus bradycardia were more common in patients with the CC genotype(P < 0.05). CONCLUSION: The Gly389Arg CC genotype of beta(1)-adrenoceptor genes may be involved in cardiovascular complication in OSAHS, and the C allele may be an important candidate gene.

[Restoration of pathological changes of emphysema by angiogenesis factors: experiment of rats].

OBJECTIVE: To investigate whether intratracheal administration of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) restore the pulmonary function and pathology in emphysema, and research the mechanism of they restored pulmonary emphysema, and the pathogenesis of pulmonary emphysema. METHODS: Twenty-four Wistar rats were randomized into the 4 equal groups: bFGF group [receiving a single intratracheal instillation of porcine pancreatic elastase (PPE) 250 U/kg, and 4 weeks later receiving intratracheal instillation of bFGF 400 U once a week for 3 weeks), VEGF group (receiving a single intratracheal instillation of PPE 250 U/kg, and 4 weeks later receiving intratracheal instillation of VEGF 2 microg once a week for 3 weeks), control group [receiving a single intratracheal instillation of PPE 250 U/kg, and 4 weeks later receiving intratracheal instillation of normal saline (NS) once a week for 3 weeks], and normal group (receiving intratracheal instillation of NS in above-mentioned pattern). Four weeks after treatment, arterial blood sample was collected from the abdominal aorta to undergo blood gas analysis for assessment pulmonary function, and then the rata were killed with their lungs taken out to undergo pathological examination. Immunohistochemistry was performed to detect the CD34, markers of pulmonary capillary endothelial cells. RESULTS: There were no significant differences in the artery blood gas analysis among the four groups (all P > 0.05). The levels of mean alveoli number (MAN) of the bFGF and VEGF groups were (43 +/- 8)/HP and (44 +/- 9)/HP] respectively, both significantly higher than that of the control group [(30 +/- 6)/HP, both P < 0.01]. The levels of mean linear intercept (MLI) of the bFGF and VEGF groups were (196 +/- 38) microm and (194 +/- 38) microm respectively, both significantly lower than that of the control group [(288 +/- 68) microm, both P < 0.01). the mean alveoli area (MAA) level of the bFGF and VEGF groups were (9856 +/- 1864) microm(2) and (9804 +/- 1929) microm(2) respectively, both significantly lower than that of the control group [(14,525 +/- 3408) microm(2), both P < 0.01]. The percentages of CD34(+) cells of the bFGF and VEGF groups were (3.7 +/- 1.3)% and (2.6 +/- 1.2)% respectively, both significantly higher than that of the control group [(0.8 +/- 0.7)%, both P < 0.05). CONCLUSION: bFGF and VEGF can restore the pathological changes of experimental emphysema. The damage of pulmonary capillary may play an important role in the pathogenesis of pulmonary emphysema.

[The effects of bilirubin concentration on laminin and epidermal growth factor expression in lung tissue and type II pneumocytes in smoking rats model].

OBJECTIVE: To explore the effects of bilirubin on expression of laminin (Ln) and epidermal growth factor (EGF) in lung tissue and in type II pneumocytes (ATII) in smoking rats. METHODS: 36 healthy Wistar rats were randomly divided into three groups: a normal group, a smoking-induced emphysema model group (model group), and a bilirubin group (n = 12, for each group). According to XU San-lin method, rats both in the model group and the bilirubin group were exposed to smoke for a total of 6 months. Rats in the bilirubin group were pretreated with indirect bilirubin (20 mg.kg(-1).d(-1)) before exposed to smoke once a day. All animals were sacrificed six months later. ATIIwere isolated, purified and cultured. Ln in ATII culture medium was determined by radioimmunoassay (RIA). We detected Ln in lung tissue with indirect immunofluorescence technique and EGF with immunochemistry. RESULTS: In the model group, Ln content in ATII culture medium and in lung tissue [(5.0 +/- 0.3) mg/ml, 5.67 +/- 0.26] increased significantly compared with those in the normal group [(3.2 +/- 0.5) mg/ml, 2.01 +/- 0.74; P < 0.05, respectively]. In the bilirubin group, the two indexes [(3.9 +/- 0.7) mg/ml, 4.18 +/- 0.63] decreased significantly compared with those in the model group (P < 0.05, respectively), which was higher than the normal group (P < 0.05). Expression of EGF in lung tissue of the model group (0.43 +/- 0.09) increased significantly compared with that of the normal group (0.14 +/- 0.02; P < 0.05). The expression of EGF in the bilirubin group (0.34 +/- 0.03) decreased significantly compared with the model group (P < 0.05), which was higher than that of the normal group. CONCLUSIONS: Bilirubin was shown to be able to promote the reconstruction of extracellular matrix by decreasing the expression of Ln and EGF in lung tissue and in ATII in the development of emphysema.

[Epidemiological studies of sleep apnea-hypopnea syndrome: a questionnaire survey of Taiyuan].

OBJECTIVE: To obtain the epidemiological data of sleep apnea-hypopnea sydrome (SAHS) in Taiyuan. METHODS: A questionnaire survey was performed in 6 028 people living in Taiyuan. The prevalence of SAHS was estimated by a two-stage procedure. In the first stage, stratified cluster disproportional random sampling survey was performed in Taiyuan. 6 028 questionnaires were send to random sample of defined population in the 4 sites selected from 2 districts. The response rate was 85.11%. During the second stage 476 of those highly suspected of having SAHS (ESS >/= 9) underwent all-night polysomnographic (PSG) studies. RESULTS: From the study population, 179 were diagnosed as having SAHS. The overall prevalence was 3.5% (male 4.7% and female 1.9%). CONCLUSION: The prevalence of SAHS was 3.5% among Taiyuan.