[The regulative effcets of A2a adenosine receptor on expression of SOCS-3 in rats of hypoxic pulmonary hypertension].
Zhonghua Jie He He Hu Xi Za Zhi
; 39(6): 469-73, 2016 Jun.
Article
em Zh
| MEDLINE
| ID: mdl-27289578
ABSTRACT
OBJECTIVE:
To study the regulative effects and mechanism of A2aAR on expression of suppressor of cytokinesignaling-3(SOCS-3) in hypoxic pulmonary hypertension rats.METHODS:
Sprague-Daeley rats were randomly divided into 3 groups a normal control group, a hypoxia group, and a hypoxia with selective agonists of A2aAR group. Animals in the hypoxia groups were housed in a chamber with 8%- 11% O2 and 1%-3% CO2 for 8 hours (8 00 AM to 4 00 PM) daily for 28 days. They were treated intraperitoneally with either 4 ml/kg weight of normal saline or 0.2 mg/kg weight of CGS-21680 30 minutes before exposure to hypoxia. Four weeks later, mean pulmonary artery pressure (mPAP), mean carotid arterial pressure (mCAP) and right ventricular rate [RV/(LV+ S)] were measured. The expression of A2aAR and SOCS-3 in pulmonary arterioles was measured by immunohistochemistry. The expression of A2aAR mRNA and SOCS-3 mRNA in lung tissues were measured by real time RT-PCR. The expression of A2aAR protein and SOCS-3 protein in lung tissues were measured by Western blot.RESULTS:
The mPAP in the hypoxia group was [(20.9±3.9)mmHg, 1 mmHg=0.133 kPa], significantly higher than the normal control group [(12.6±6.6)mmHg](P<0.01). The mPAP in CGS-21680 group was [ (14.8±3.8)mmHg], significantly lower than the hypoxia group(P<0.01). RV/(LV+ S) in the hypoxia group was [(35.2±2.0)%] , significantly higher than the normal control group [(29.6±2.7)%] (P<0.01). RV/(LV+ S) in the CGS-21680 group was [(28.3±8.8)%], significantly lower than the hypoxia group(P<0.01). WA/TA in the hypoxia group was (73±5, P<0.01), significantly higher than the normal control group. WA/TA in CGS21680 group was (54±3, P<0.01), significantly lower than the hypoxia group. A2aAR and SOCS-3 expressions on pulmonary arterioles in the hypoxia group were (0.134±0.034) and (0.119±0.011), both significantly higher than the normal group(P<0.01); and CGS-21680 treatment further increased their expressions. The mRNA expression of both molecules showed a 1.5-fold increase after 28-day hypoxia exposure. A2aAR activation by CGS-21680 treatment in hypoxia-exposed rats further increased the expression levels of A2aAR and SOCS-3 to about 2-fold higher than the normal controls. Furthermore, protein levels of A2aAR and SOCS-3 in the lung tissue were determined using Western blot. A similar increase was observed in hypoxia-induced pulmonary hypertension, and CGS-21680 treatment group showed the highest levels of these 2 proteins.CONCLUSION:
A2aAR activation prevents hypoxia-induced pulmonary hypertension, and its mechanisms are related to the activation of A2aAR SOCS-3 signaling pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores A2 de Adenosina
/
Proteína 3 Supressora da Sinalização de Citocinas
/
Hipertensão Pulmonar
Limite:
Animals
Idioma:
Zh
Ano de publicação:
2016
Tipo de documento:
Article