硫化氢对自发性高血压大鼠血管炎症反应的调节作用

Hypotensive effects of hydrogen sulfide via attenuating vascular inflammation in spontaneously hypertensive rats

目的探讨新型气体信号分子硫化氢（H2S）对自发性高血压大鼠（SHR）血管炎症反应的调节作用。方法4周龄Wistar-Kyoto（WKY）雄性大鼠和SHR雄性大鼠分为4组：WKY大鼠对照组、SHR对照组、SHR＋硫氢化钠（NariS，H2S供体）组及SHR＋炔丙基甘氨酸（PPG，H2S生成关键酶抑制剂）组，饲养至9周。尾容积法测清醒时大鼠血压，免疫组织化学方法检测主动脉内皮细胞膜细胞间黏附分子-1（ICAM-1）、核转录因子-κB p65（NF-κB p65）和核转录因子抑制因子-α（IκB-α）的蛋白表达，原位杂交分析检测主动脉内皮细胞ICAM-1 mRNA的表达。结果SHR对照组血压显著高于WKY对照组（P〈0．05），主动脉内皮细胞ICAM-1、ICAM-1 mRNA、胞核NF-κB p65明显高（P均〈0．01），胞浆IκB-α蛋白表达明显低（P〈0．01）。SHR＋NariS组血压显著低于SHR对照组，主动脉内皮细胞ICAM-1、ICAM-1 mRNA、胞核NF-κB p65蛋白表达明显低（P〈0．05），胞浆IκB-α蛋白表达明显增高（P〈0．05），SHR＋PPG组主动脉内皮细胞ICAM-1、ICAM-1 mRNA、胞核NF-κB p65蛋白表达更高（P〈0．05），胞浆IκB-α蛋白表达显著低（P〈0．05）。结论H2S可通过抑制SHR血管炎症发挥抗高血压效应。H2S的抗血管炎症效应可能通过上调IκB-α的表达，降低NF-κB p65的表达，抑制ICAM-1 mRNA的转录和蛋白表达实现。

Objective To investigate the effects of hydrogen sulfide （H2S） on vascular inflammation and blood pressure in spontaneously hypertensive rats （SHR）. Methods Four weeks old male SHR rats were treated with saline （control, n = 7） , sodium hydrosulfide （NariS, a H2S donor, n = 7 ） and propargylglycine （ PPG, endogenous H2S production inhibitor, n = 6） for 5 weeks. Age-natched male Wistar Kyoto （WKY） rats served as normotensive controls （ n = 8 ）. Five weeks later, systolic blood pressure （SBP） was measured in conscious and quiet rats by means of the standard tail-cuff method. The protein expressions of intercellular adhesive molecule-1 （ ICAM-1 ）, nuclear transcriptional factor-κB p65 （ NF-κB p65） and inhibitor of nuclear transcriptional factor-κB （IκB-α） in thoracic aorta of rats were detected by immunohistochemical assay, while the expression of ICAM-1 mRNA in thoracic aorta of rats were investigated by in situ hybridization. Results SBP of control SHR rats was significantly higher than that of WKY rats （ P 〈 0.05 ） accompanied by significantly upregulated expressions of ICAM-1 mRNA, ICAM-1 protein, NF-κB 1365 protein in aortic endothelial cells （ all P 〈 0. 01 ）, while the expression of IκB-α protein in aortic endothelial cells in SHR control group was significantly lower than that of WKY control group （P 〈 0. 01 ）. NariS treated SHR rats showed significantly reduced SBP and downregulated expressions of ICAM-1 mRNA, ICAM-1, NF-κB p65 in aortic endothelial cells and upregulated expression of IκB-α protein in aortic endothelial cells compared to untreated control SHR rats （ all P 〈 0. 05）. In SHR rats treated with PPG, the expressions of ICAM-1 mRNA, ICAM-1 protein, NF-κB p65 protein in aortic endothelial cells were further increased while the expression of IκB-α protein further decreased compared with control SHR rats （all P 〈 0. 05 ） . Conclusion H2S might attenuate the development of hypertension through by attenuating vascular inflammation reactions.