色甘酸钠对肺动脉高压大鼠肥大细胞功能的抑制作用

摘要

Objective To investigate the inhibitory effects of cromoglicate sodium on the mast cells in rats with lung arterial hypertrophy, and to investigate the correlation between the function of mast cells and pulmonary vascular re-modeling.Methods The constriction operation on the openings above coronary aorta ( supracoronary aortic banding) was performed on male adult SD rats to establish the PH-LHD rat models.Cromoglicate sodium was given to the treatment group, while replaced saline was given to the rats in model group and sham operation group.Pulmonary vascular remode-ling, and mast cell aggregation and degranulation were observed, while peripheral MCP-1 and IL-6 were assessed using ELISA.Results Mast cell accumulation around pulmonary arterioles was observed on the 36th day, which was alleviated by cromoglicate sodium treatment.The peripheral MCP-1 and IL-6 were significantly elevated in model group when comparing with those in the other 2 groups, which was significantly reduced by cromoglicate sodium treatment ( P <0.05 ) .Conclusion Mast cell accumulation and degranulation around pulmonary arterioles with diameter between 20 and 50 μm plays important role in the pathogenesis of pulmonary hypertension.Membrane stabilizer, cromoglicate sodium, can reduce the inflammatory factors, including MCP-1 and IL-6, thus to inhibit the function of mast cells.%目的：观察色甘酸钠对肺动脉高压大鼠血管周边肥大细胞聚集的抑制作用，评价其时间相关性，找寻肥大细胞稳定剂治疗的最佳时机。方法选取18只雄性未成年SD大鼠，随机分对照组、假手术组和模型组，对照组大鼠未做任何处理，当天即进入实验程序；假手术组大鼠行假手术后64 d进入实验程序；模型组大鼠通过实施升主动脉缩窄手术来制备“左心疾病所致的肺动脉高压”模型，手术前5 d至造模术后第15、22、36、50天，分别腹腔注射色甘酸钠25 mg／（ kg· d），假手术组和对照组从腹腔注射等剂量的生理盐水。结果20～50μm肺血管周边，在第36天时均发生明显的肥大细胞聚集现象，采用色苷酸钠干预后肥大细胞功能受到抑制；模型组血清MCP－1和IL－6明显较其他组升高，而采用色苷酸钠干预后水平明显下降，其差异均有统计学意义（ P＜0.05）。结论20～50μm肺细血管周围肥大细胞的聚集及脱颗粒是肺动脉高压的重要变化，采用细胞膜稳定剂色苷酸钠可以降低炎症因子MCP－1和IL－6水平，抑制肥大细胞功能。