阿司匹林对控制大鼠盐敏感性高血压的作用机制研究
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摘要
目的探讨阿司匹林对大鼠盐敏感性高血压的调节作用及相关机制。方法 2月龄盐敏感性大鼠(Dahl SS)及其对照盐耐受性大鼠(SS-13BN)分别给予低盐(0. 12%NaCl,LS)、高盐(8%NaCl,HS)、高盐加阿司匹林灌胃((10 mg/(kg·d)),HS+ASA)饲养至8周,期间尾袖法连续测量动脉血压,8周后颈总动脉插管测量大鼠动脉血压,Real-time PCR检测肾组织炎症因子IL-6、IL-1β、TNF-α的表达,免疫荧光检测皮肤M2型巨噬细胞的数量,免疫印迹检测血管功能代表性蛋白eNOS、vWF的表达。结果 Dahl SS大鼠高盐喂养后,血压明显升高,肾组织炎症因子和血管vWF因子表达量显著增加、皮肤M2型巨噬细胞数量及血管eNOS表达量明显减少,阿司匹林能够有效改善Dahl SS大鼠高盐诱导的血压升高、炎症反应及血管功能的损伤,而SS-13BN大鼠并未出现上述情况。结论阿司匹林通过抗血小板功能抑制了Dahl SS大鼠由高盐诱导的炎症反应,抑制了血管功能损伤及高血压发生发展。
Objective To investigate the mechanism of aspirin on high salt-induced hypertension in Dahl saltsensitive rats. Methods Two-month-old Dahl salt-sensitive rats( Dahl SS) and salt-resistant rats( SS-13 BN) were fed with Low salt( 0. 12% Na Cl,LS),High salt( 8% Na Cl,HS),High salt + Aspirin( 8% NaCl +10 mg/( kg·d) aspirin),or HS+ ASA for 8 weeks. Blood pressure was measured by the tail cuff method. The expressions of renal inflammatory cytokines( IL-6,IL-1β,TNF-α) and eNOS and vWF in arteries were measured by real-time PCR and western blot,respectively. The number of skin M2 macrophages was measured by immunofluorescence. Results Blood pressure,expressions of renal IL-6,IL-1β,TNF-α,and arterial vWF were markedly increased,and the number of M2 macrophages in the skin,and eNOS expression in the arteries were significantly decreased in the high salt group compared with the low salt group. Aspirin inhibited all these events in rats on a high salt diet. However,the influence of high salt and aspirin wasnot observed in SS-13 BN rats. Conclusions Aspirin attenuated salt-sensitive hypertension and arterial injury induced by a high salt diet in Dahl salt-sensitive rats via inhibiting platelet activated inflammation.
Objective To investigate the mechanism of aspirin on high salt-induced hypertension in Dahl saltsensitive rats. Methods Two-month-old Dahl salt-sensitive rats( Dahl SS) and salt-resistant rats( SS-13 BN) were fed with Low salt( 0. 12% Na Cl,LS),High salt( 8% Na Cl,HS),High salt + Aspirin( 8% NaCl +10 mg/( kg·d) aspirin),or HS+ ASA for 8 weeks. Blood pressure was measured by the tail cuff method. The expressions of renal inflammatory cytokines( IL-6,IL-1β,TNF-α) and eNOS and vWF in arteries were measured by real-time PCR and western blot,respectively. The number of skin M2 macrophages was measured by immunofluorescence. Results Blood pressure,expressions of renal IL-6,IL-1β,TNF-α,and arterial vWF were markedly increased,and the number of M2 macrophages in the skin,and eNOS expression in the arteries were significantly decreased in the high salt group compared with the low salt group. Aspirin inhibited all these events in rats on a high salt diet. However,the influence of high salt and aspirin wasnot observed in SS-13 BN rats. Conclusions Aspirin attenuated salt-sensitive hypertension and arterial injury induced by a high salt diet in Dahl salt-sensitive rats via inhibiting platelet activated inflammation.
引文
[1]陈巍,杨志伟.盐敏感性高血压相关生物学研究进展[J].中华高血压杂志,2014,22(12):1126-1131.
[2]王占芬,张学艳,任秉丽,等.进展性脑卒中危险因素分析及与H型高血压的相关性研究[J].中国实用神经疾病杂志,2016,19(13):60-62.
[3]毛红亚,刘云鹏,王子皓,等.血小板通过炎症反应在盐敏感性高血压中的作用机制研究[J].中国比较医学杂志,2017,27(5):23-30.
[4] Stokes KY, Granger DN. Platelets:a critical link between inflammation and microvascular dysfunction[J]. J Physiol,2012,590(5):1023-1034.
[5] Harrison DG,Vinh A,Lob H,et al. Role of the adaptive immune system in hypertension[J]. Curr Opin Pharmacol,2010,10(2):203-207.
[6] Rondina MT,Weyrich AS,Zimmerman GA. Platelets as cellular effectors of inflammation in vascular disease[J]. Circ Res,2013,112(11):1506-1519.
[7] Gawaz M,La nger H,May AE. Platelets in inflammation and atherogenesis[J]. Clin Invest 2005,115:3378-3384.
[8] Tsoumani, ME, et al. Platelet-mediated inflammation in cardiovascular disease. Potential role of platelet-endothelium interactions[J]. Curr Vasc Pharmacol,2012,10(5):539
[9] Lehoux S,Jones EA. Arterial identity and atherosclerosis[J].Thromb Haemost. 2016,115(3):467-473.
[10] Herzog BH,Fu J,Wilson SJ,et al. Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2[J]. Nature,2013,502:105-109.
[11] Larrousse M,Bragulat E,Segarra M,et al. Increased levels of atherosclerosis markers in salt-sensitive hypertension[J]. Am J Hypertens,2006,19(1):87-93.
[12] Bibbins-Domingo K. U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer:U. S. Preventive Services Task Force Recommendation Statement[J]. Ann Intern Med,2016,164(12):836-845.
[13] Felder RA,White MJ,et al. Diagnostic tools for hypertension and salt sensitivity testing[J]. Curr Opin Nephrol Hypertens,2013,22(1):65-76.
[14] Baldo MP, Rodrigues SL, Mill JG. High salt intake as a multifaceted cardiovascular disease:new support from cellular and molecular evidence[J]. Heart Fail Rev,2015,20(4):461-474.
[15] Rondina MT,Weyrich AS,Zimmerman GA. Platelets as cellular effectors of inflammation in vascular diseases[J]. Circ Res,2013,112:1506-1519.
[16] Bernardo A,Ball C,Nolasco L,Choi H,Moake JL,Dong JF.Platelets adhered to endothelial cell-bound ultra-large von Willebrand factor strings support leukocyte tethering and rolling under high shear stress[J]. Thromb Haemost,2005,3(3):562-570.
[17] Saito Y,Okada S,Ogawa H,et al. Low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus:10-year follow-up of a randomized controlled trial[J].Circulation,2017,135(7):659-670.
[18] Wu R,Lamontagne D,de Champlain J. Antioxidative properties of acetylsalicylic acid on vascular tissues from normotensive and spontaneously hypertensive rats[J]. Circulation,2002,105(3):387-392.
[19] Weitz JI,Lensing AWA,Prins MH,et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism[J]. N Engl J Med,2017,376(13):1211-1222.
[20] Cahill PA,Redmond EM. Vascular endothelium-gatekeeper of vessel health[J]. Atherosclerosis,2016,248:97-109.
[2]王占芬,张学艳,任秉丽,等.进展性脑卒中危险因素分析及与H型高血压的相关性研究[J].中国实用神经疾病杂志,2016,19(13):60-62.
[3]毛红亚,刘云鹏,王子皓,等.血小板通过炎症反应在盐敏感性高血压中的作用机制研究[J].中国比较医学杂志,2017,27(5):23-30.
[4] Stokes KY, Granger DN. Platelets:a critical link between inflammation and microvascular dysfunction[J]. J Physiol,2012,590(5):1023-1034.
[5] Harrison DG,Vinh A,Lob H,et al. Role of the adaptive immune system in hypertension[J]. Curr Opin Pharmacol,2010,10(2):203-207.
[6] Rondina MT,Weyrich AS,Zimmerman GA. Platelets as cellular effectors of inflammation in vascular disease[J]. Circ Res,2013,112(11):1506-1519.
[7] Gawaz M,La nger H,May AE. Platelets in inflammation and atherogenesis[J]. Clin Invest 2005,115:3378-3384.
[8] Tsoumani, ME, et al. Platelet-mediated inflammation in cardiovascular disease. Potential role of platelet-endothelium interactions[J]. Curr Vasc Pharmacol,2012,10(5):539
[9] Lehoux S,Jones EA. Arterial identity and atherosclerosis[J].Thromb Haemost. 2016,115(3):467-473.
[10] Herzog BH,Fu J,Wilson SJ,et al. Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2[J]. Nature,2013,502:105-109.
[11] Larrousse M,Bragulat E,Segarra M,et al. Increased levels of atherosclerosis markers in salt-sensitive hypertension[J]. Am J Hypertens,2006,19(1):87-93.
[12] Bibbins-Domingo K. U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer:U. S. Preventive Services Task Force Recommendation Statement[J]. Ann Intern Med,2016,164(12):836-845.
[13] Felder RA,White MJ,et al. Diagnostic tools for hypertension and salt sensitivity testing[J]. Curr Opin Nephrol Hypertens,2013,22(1):65-76.
[14] Baldo MP, Rodrigues SL, Mill JG. High salt intake as a multifaceted cardiovascular disease:new support from cellular and molecular evidence[J]. Heart Fail Rev,2015,20(4):461-474.
[15] Rondina MT,Weyrich AS,Zimmerman GA. Platelets as cellular effectors of inflammation in vascular diseases[J]. Circ Res,2013,112:1506-1519.
[16] Bernardo A,Ball C,Nolasco L,Choi H,Moake JL,Dong JF.Platelets adhered to endothelial cell-bound ultra-large von Willebrand factor strings support leukocyte tethering and rolling under high shear stress[J]. Thromb Haemost,2005,3(3):562-570.
[17] Saito Y,Okada S,Ogawa H,et al. Low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus:10-year follow-up of a randomized controlled trial[J].Circulation,2017,135(7):659-670.
[18] Wu R,Lamontagne D,de Champlain J. Antioxidative properties of acetylsalicylic acid on vascular tissues from normotensive and spontaneously hypertensive rats[J]. Circulation,2002,105(3):387-392.
[19] Weitz JI,Lensing AWA,Prins MH,et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism[J]. N Engl J Med,2017,376(13):1211-1222.
[20] Cahill PA,Redmond EM. Vascular endothelium-gatekeeper of vessel health[J]. Atherosclerosis,2016,248:97-109.
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