阿魏酸钠对慢性低氧大鼠肺血管重建的影响及作用机制

摘要

Objective To investigate the effect of sodium ferulate on vascular morphologic indexes of pul-monary,expression of p53 and PCNA, cell proliferation and apoptosis in chronic hypoxic rats. Methods Thirty healthy Spraque-Dawley male rats were randomly divided into three groups: normal control group (n = 10), chronic hypoxic group (n = 10) and hypoxia plus sodium ferulate treatment group (n = 10). The model of chronic hypoxic pulmonary hypertension was established by exposing rats to normobaric hypoxic conditions for 8 hours one day in 3 weeks continually. Effects of sodium ferulate on vascular morphologic indexes of pulmonary, expression of P53 and PCNA, cell proliferation and apoptosis in pulmonary tissue of HPH rats were observed. Results After 21 days, rats in chronic hypoxic group in MT%, MA%, PI, expression of p53 are obviously higher than normal control group (P < 0.01 ), in VA%, AI are distinctly higher than normal control group (P < 0.01);Rats of hypoxia plus sodium ferulate treatment group in MT%, MA%, PI and expression of p53 are obviously decreased than chronic hypoxic group (P < 0.01 or P < 0.05 ), in VA% and AI are increased higher than chronic hypoxic group (P < 0.01);Ex-cept that VA% ,AI and expression of p53 have meaning (P < 0.01 or P < 0.05 ), other indexes have no meaning compared with normal control group (P > 0.05). Conclusion Sodium ferulate can refrain persistently from the de-velopment of pulmonary vascular remodeling efficiently in chronic hypoxic rats. The mechanism may be related to in-hibiting the protein expression of p53 and PCNA, enhancing cell proliferation and decreasing cell apoptosis.%目的 研究阿魏酸钠对慢性低氧大鼠肺血管形态、p53及PCNA蛋白表达及细胞增殖与凋亡的影响.方法 30只雄性SD大鼠采用随机单位组设计方法分为对照组、低氧组和联合治疗组,每组10只.采用常压间断低氧8h/d,连续21d的方法复制慢性低氧性肺动脉高压模型.对照组吸入空气(其他条件与低氧组相同).联合治疗组大鼠腹腔注射15 ms/(kg·d)的阿魏酸钠.观察阿魏酸钠对慢性低氧大鼠肺血管形态学指标、p53及增殖细胞核抗原PCNA基因蛋白表达、细胞的增殖与凋亡的影响.结果 低氧21 d后,低氧组管壁厚度占血管外径的百分比、管壁面积占血管总面积的百分比、增殖指数及p53基因表达较对照组均明显升高(P<0.01),管腔面积占血管总面积的百分比、凋亡指数较对照组明显降低(P<0.01);联合治疗组管壁面积占血管总面积的百分比、管壁厚度占血管外径的百分比、增殖指数及p53基因表达与低氧组相比明显降低,差别有统计学意义(P<0.01或P<0.05).管腔面积占血管总面积的百分比、凋亡指数与低氧组相比明显升高,差别有统计学意义(P<0.01);联合治疗组除管腔面积占血管总面积的百分比、凋亡指数及p53基因表达与对照组差异有统计学意义(P<0.01或P<0.05)外,其他指标与对照组比较差异均无统计学意义(P>0.05).结论 阿魏酸钠可抑制慢性低氧大鼠肺血管重建,其机制可能与抑制p53及PCNA基因的表达,导致细胞增殖被抑制、细胞凋亡被促进等有关.