腺苷A_1受体激动剂拮抗大鼠慢性低氧所致右心室肥厚的实验研究

Effects of A_1 adenosine receptor agonists on RGS_4 in hypoxia-induced right ventricular hypertrophy in rats

目的通过外周途径持续给予腺苷A1受体激动剂2-氯环戊腺苷(CPA),观察其拮抗低氧致右心室肥厚的作用和机制。方法将24只SD大鼠随机分为3组:A组(常氧组)、B组(慢性低氧组)、C组(慢性低氧+CPA治疗组)。B、C组于缺氧箱中喂养。于实验第8天予皮下埋泵给予CPA。于第21天处死大鼠,检测右心室/(左心室+室间隔)[RV/(LV+S)]、右心室/体重(RV/BW)比值;采用RT-PCR及Western-blot法检测RGS4基因及蛋白表达。结果慢性缺氧组与常氧组相比,RV/(LV+S)、RV/BW比值明显增高(分别P<0.01,P<0.05),而RGS4的mRNA及蛋白表达水平明显下降(均P<0.01);CPA处理后RV/(LV+S)、RV/BW比值明显低于缺氧组(分别P<0.01,P<0.05),而RGS4的mRNA及蛋白表达水平明显增高(P均<0.01)。结论外周途径应用CPA能拮抗慢性缺氧所致右心肥厚,其机制可能是通过上调RGS4表达从而抑制G蛋白介导的信号通路。

Objective To investigate the attenuated effects of 2-chloro-N6-cyclopentyladenosine （CPA） on right ventricular hypertrophy （RVH） induced by.chronic hypoxia in rats by subcutaneous route and the mechanism. Methods Used randomized block design based on different brood, 24 rats were divided into three groups.. C.. treatment group with CAP, B.. chronic hypoxia group and A： normal control group. The rats in CAP-treated group and chronic hypoxia group were exposed to normobaric chronic hypoxia. On the 21st day of the experiment, the changes of RV weight to left ventricle and interventricular septum weight ratio FRV/（LV ＋ S）], the RV weight to body weight ratio （RV/BW）, the expression levels of RGS4 mRNA and protein were observed. Results RV/（LV ＋ S） and RV/BW in chronic hypoxia group were higher than in normal control group （both P〈0.01） and the CPA-treated group （P〈0.01, P〈0.05, respectively）. The expression levels of RGS4 mRNA and protein in RV of chronic hypoxia group were lower than in the normal control group （both P〈0. 01） and higher than in the CAP-treated group （both P〈0.01）. Conclusion Continuous administration of CPA by subcutaneous route can attenuate myo- cardial hypertrophy and increase the gene expression of RGS4 in RVH induced by chronic hypoxia in rats. CPA can suppress the development of RVH through inhibiting the G protein-mediated signaling pathway.