【摘要】 目的观察JNK信号通路对阻塞性睡眠呼吸暂停(OSA)合并高血压的调控模式。方法选取生长发育正常大鼠36只,随机分为常氧对照组、常氧干预组、间歇性低氧组、间歇性低氧干预组,每组9只。JNK阻滞剂对两干预组大鼠进行灌胃,后将间歇性低氧组大鼠进放置在低压氧舱内,制作OSA大鼠模型;使用血压计测量各组大鼠12周的平均动脉血压,并在12周末处死大鼠,予大鼠腹主动脉行HE染色查看病理学结果,采用RT-PCR法和Western blot法检测腹主动脉JNK-1的m RNA和蛋白的表达水平。结果 (1)与常氧对照组比较,间歇性低氧组大鼠血压升高(P<0.05);与间歇性低氧组比较,间歇性低氧干预组大鼠血压下降(P<0.05);(2)与间歇性低氧组比较,间歇性低氧干预组中腹主动脉中膜血管平滑肌细胞(VSMCs)数量下降(P<0.05),血管管壁厚度无增加,未见纤维蛋白堆积,无明显内皮细胞表型转化表现,与常氧干预组大鼠比较,间歇性低氧干预组大鼠腹主动脉中膜VSMC层数未增加或减少(P>0.05);(3)与常氧对照组比较,JNK-1mRNA在间歇性低氧组中表达升高(P<0.05);与间歇性低氧组比较,干预组JNK-1mRNA表达量降低(P<0.05);(4)与常氧对照组比较,间歇性低氧组JNK-1蛋白表达水平增加(P<0.05);与间歇性低氧组比较,干预组蛋白表达水平降低(P<0.05)。结论间歇性低氧可引起高血压,并介导大鼠腹主动脉出现血管重构,可能与JNK信号通路的激活有关。更多还原

【Abstract】 Objective To study the model of JNK pathway on obstructive sleep apnea with hypertension.Methods Thirty-six rats with normal growth and development were randomly divided into normoxia control group, normoxia intervention group, intermittent hypoxia group and intermittent hypoxia intervention group, with 9 rats in each group. JNK inhibitor was administered intragastrically to rats in the two intervention groups, and then rats in the intermittent hypoxia group were placed in the low pressure oxygen chamber to make OSA rat model. The mean arterial blood pressure of rats in each group at 12 weeks was measured by a sphygmomanometer, and the rats were sacrificed at the end of 12 weeks. The abdominal aorta of rats was stained with HE to examine the pathological results. The mRNA and protein expression levels of JNK-1 in the abdominal aorta were detected by RTPCR and Western blot.Results(1)Compared with normoxia control group, the blood pressure of rats in intermittent hypoxia group increased( P<0.05);compared with the intermittent hypoxia group, the blood pressure of rats in the intermittent hypoxia intervention group decreased( P <0.05).(2)Compared with the intermittent hypoxia group, the number of vascular smooth muscle cells(VSMCs) in the middle abdominal aorta in the intermittent hypoxia intervention group decreased(P<0.05), there was no increase in vessel wall thickness, no fibrin accumulation, and no obvious phenotypic transformation of endothelial cells; compared with rats in the normoxic intervention group, the number of VSMC layers in the abdominal aorta of rats in the intermittent hypoxia intervention group did not increase or decrease(P>0.05).(3)Compared with normoxic control group, the expression of JNK-1 mRNA in intermittent hypoxia group increased(P <0.05);compared with the intermittent hypoxia group, the expression of JNK-1 mRNA in the intervention group decreased(P<0.05).(4)Compared with normoxia group, the expression of JNK-1 protein in intermittent hypoxia group was increased(P<0.05); compared with intermittent hypoxia group, protein expression in intervention group decreased( P<0.05).Conclusion Intermittent hypoxia can cause hypertension and mediate vascular remodeling in rat abdominal aorta, which may be related to the activation of JNK signaling pathway.更多还原