腺苷2B受体激动剂对大鼠高原肺水肿的治疗作用

Therapeutic Effect of Adenosine 2B Receptor Agonist on High-Altitude Pulmonary Edema in Rats

目的研究腺苷2B受体激动剂BAY60-6583对高原肺水肿的治疗作用。方法24只SD雄性大鼠随机分为平原对照组(Control组)、高原肺水肿模型组(HAPE组)和BAY60-6583干预组(BAY组),每组8只。除Control组外,HAPE组及BAY组均以10 m/s的速度上升至模拟海拔6000 m高度并维持48 h。出舱后BAY组腹腔注射BAY60-6583[2 mg/(kg·d)],Control组及HAPE组腹腔注射等体积溶媒,持续3 d。大鼠麻醉后收集血液和组织标本,取肺叶HE染色观察肺组织病理变化,测定肺含水量、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、肿瘤坏死因子-α(TNF-α)含量、白介素(IL)-6含量、环磷酸腺苷(cAMP)含量和上皮Na+通道α亚基(ENaC-α)的基因相对表达量与蛋白含量。结果与Control组相比,HAPE组肺组织出现明显病理学变化,肺含水量升高,TNF-α、IL-6和MDA含量升高,SOD活性和ENaC-α明显降低(P<0.05);与HAPE组相比,BAY组肺组织病理学变化明显改善,肺组织含水量明显降低,TNF-α、IL-6和MDA含量降低,SOD活性、cAMP和ENaC-α明显升高(P<0.05)。结论BAY60-6583可能通过降低肺含水量、TNF-α、IL-6和MDA含量,提高SOD活性、c AMP水平和ENa C-α的含量,以减轻大鼠高原低氧环境所致的肺水肿。

Objective To study the therapeutic effect of adenosine 2 B receptor agonist BAY60-6583 on high-altitude pulmonary edema.Methods 24 male SD rats were randomly divided into plain control group(Control group),high-altitude pulmonary edema model group(HAPE group)and BAY60-6583 intervention group(BAY group),with 8 rats in each group.Except for the Control group,rats in HAPE and BAY group were raised to simulated altitude of 6000 m at a speed of 10 m/s for 48 hours.After exiting,rats in BAY group were intraperitoneally injected with BAY60-6583[2 mg/(kg·d)],and rats in Control and HAPE groups were intraperitoneally injected with equal volume of solvent for 3 days.Blood and tissue samples were collected after anesthesia.Pulmonary pathological changes were observed by HE staining.The water content of lung tissue,SOD activity,contents of MDA,TNF-α,IL-6,cAMP,and content of epithelial Na+channelαsubunit(ENaC-α)were detected.Results Compared with Control group,HAPE group showed significant pathological changes in lung tissue,with increased contents of lung water,TNF-α,IL-6 and MDA,decreased SOD activity and ENaC-αexpressions(P<0.05).Compared with HAPE group,pulmonary histopathological changes in BAY group were significantly improved,accompanied with declined water contents of lung tissue,declined contents of TNF-α,IL-6,MDA,and elevated SOD activity,cAMP and ENaC-αcontents(P<0.05).Conclusion BAY60-6583 may alleviate pulmonary edema caused by high-altitude hypoxia environment in rats by decreasing contents of lung water,TNF-α,IL-6,MDA,and increasing SOD activity,contents of cAMP and ENaC-α.