藏、汉族OSAHS患者血液流变学指标以及PI3K/AKT/NF-κB p65信号通路中HIF-1α/2α表达的差异性研究

Differences of hemorheology indexes and expression of HIF-1α/2αin PI3K/Akt/NF-kB p65 signaling pathway between Tibetan and Han OSAHS patients

目的探讨藏、汉族阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)患者的血液流变学指标与外周血单个核细胞中低氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)/低氧诱导因子2α(hypoxia-inducible factor-2α,HIF-2α)表达的差异性。方法选取藏、汉族OSAHS的重度患者各30例,同时选取同时期的健康体检者藏、汉族各30例。采用全血黏度仪检测各组受试者的全血黏度高剪切率、全血黏度低剪切率、血浆黏度比、红细胞聚集指数和红细胞比容。用实时逆转录聚合酶链反应和蛋白免疫印迹分别检测外周血单个核细胞中磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)、丝氨酸/苏氨酸激酶(serine/threonine kinase,AKT)、核因子κB(nuclear factor-κB,NF-κB)p65、HIF-1α和HIF-2α的mRNA和蛋白水平。结果藏族OSAHS患者的血液流变学指标水平均显著高于藏族健康人和汉族OSAHS患者(均P<0.05),汉族OSAHS患者的血液流变学指标水平均显著高于汉族健康人(均P<0.05)。藏族OSAHS患者外周血单个核细胞的PI3K、AKT、NF-κB p65和HIF-1αmRNA和蛋白水平水平均显著高于藏族健康人和汉族OSAHS患者(均P<0.05),汉族OSAHS患者HIF-1αmRNA和蛋白水平水平均显著高于汉族健康人(均P<0.05),而HIF-2αmRNA和蛋白水平均显著低于汉族健康人(均P<0.05)。结论OSAHS患者的外周血单个核细胞HIF-1α水平上调和HIF-2α水平下调依赖于PI3K/AKT/NF-κB p65信号通路的激活,且藏族OSAHS患者的血液流变学水平高于汉族OSAHS患者。

Objective To explore the difference between the hemorheology levels and the expression of hypoxia inducible factor 1α/2α(HIF-1α/2α)in the peripheral blood mononuclear cells of the Tibetan and Han patients with obstructive sleep apnea hypopnea syndrome(OSAHS).Methods This research recruited 30 high-risk Tibetan and Han patients with OSAHS,and 30 Tibetan and Han healthy volunteers at the same period.The whole blood viscometer was used to detect the high shear rate of whole blood viscosity,low shear rate of whole blood viscosity,plasma viscosity ratio,red blood cell aggregation index,and hematocrit in each group.RT-qPCR and Western blot assays were used to detect the mRNA and protein levels of phosphoinositide 3-kinase(PI3K),serine/threonine kinase(AKT),nuclear factor-κB(NF-κB)p65,HIF-1αand HIF-2αin peripheral blood mononuclear cells.Results The hemorheology level of Tibetan OSAHS patients was significantly higher than that of healthy Tibetans and Han OSAHS patients(P<0.05),and the hemorheology level of Han OSAHS patients was significantly higher than that of Han healthy people(P<0.05).The mRNA and protein levels of PI3K,AKT,NF-κB p65 and HIF-1αin the peripheral blood mononuclear cells of Tibetan OSAHS patients were significantly higher than those of the healthy Tibetans or Han people,and these indexes of the Han OSAHS patients were significantly higher than those of the Han healthy people(all P<0.05),while HIF-2αmRNA and protein levels were significantly lower than those of healthy Han people(all P<0.05).Conclusion The upregulation of HIF-1αlevel and downregulation of HIF-2αexpression in peripheral blood mononuclear cells of OSAHS patients depend on the activation of the PI3K/AKT/NF-κB p65 signaling pathway,and the hemorheological level of Tibetan OSAHS patients is higher than that of Han OSAHS patients.