摘要:
为探讨内源性二氧化硫(SO2)对动脉血压的影响及其信号转导通路,采用大鼠颈动、静脉插管技术研究SO2对动脉压调节作用,通过离体血管环灌流试验观察SO2对NE引起的主动脉血管环收缩作用的影响,用生物化学方法与实时定量RT-PCR技术研究SO2对离体血管一氧化氮(NO)生成、一氧化氮合酶(NOS)活性和基因表达的调节作用。结果表明:(1)静脉注入SO2(20和60μmol·kg-1体重)可立即引起大鼠动脉血压剂量依赖性显著下降,而相同剂量的亚硫酸钠和亚硫酸氢钠混合液(摩尔比为3:1)未见影响;(2)SO2对NE的缩血管功能有显著抑制作用,使NE的量效曲线右移;(3)SO2能迅速促进内皮NOS(eNOS)的基因表达,增强eNOS的活性,但对诱导型NOS(iNOS)的活性未见影响;(4)SO2可迅速且显著增加主动脉组织的NO产量。此外,我们以前的研究也指出,低浓度SO2可引起内皮细胞膜BKCa离子通道开放。由此结论:内源性SO2是一种血管活性因子,对整体血压和血管张力具有调节作用;SO2对血管BKCa→eNOS→NO→cGMP信号通路的上调可能是其主要的作用机制。
Abstract:
To explore effects of endogenous sulfur dioxide(SO2) on arterial blood pressure of rat and its signal transduction mechanisms,rat arterial blood pressure and heart rate were measured with the carotid and jugular catheterization via MedLab bio-signal collection system.Effects of SO2 on vasoconstriction induced by NE(Noradrenaline) were investigated using rat thoracic aortic ring perfusion technique.Effects of SO2 on nitric oxide synthase(NOS) activity,endothelial NOS(eNOS) gene expression,nitric oxide(NO) biosynthesis in rat vascular tissues were studied with biochemical methods and real-time RT-PCR technique.Results are as follows:(1) The venous transfusion of SO2(20,60μmol·kg-1w.t.) lowered immediately blood pressure in a dose-dependent manner in rats.However,at same dosages solution of sodium sulfite and sodium bisulfite mixture(3:1,molar ratio),it could not cause any change;(2) The vasoconstriction induced by NE was significantly depressed by SO2 and the concentration-effect curve was shifted to the right;(3) SO2 could immediately potentiate expression of eNOS gene and increase activity of eNOS,but did not induced NOS(iNOS);(4) SO2 enhanced immediately NO formation in aortic tissue.Furthermore,our previous findings indicated that SO2 at low concentrations could cause opening of BKCa on vascular endothelium cell membrane.It was concluded that SO2 was a vasoactive factor,it might regulate vascular tone and blood pressure in vivo by the mechanisms which SO2 upregulated BKCa→eNOS→NO→cGMP signal pathway.
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