期刊文献+

左旋精氨酸恢复eNOS和iNOS平衡并抑制肺动脉高压的研究 被引量:10

L-arginine inhibits pulmonary hypertension by restoring the balance between endothelial nitric oxide synthase and inducible nitric oxide synthase
原文传递
导出
摘要 目的探讨诱导型一氧化氮合酶(iNOS)在中、晚期肺动脉高压(PH)发病中的作用机制及左旋精氨酸(L—Arg)对其产生的影响。方法30只雄性sD大鼠随机均分为5组,对照组(C组)、MCT3组(M3组)、MCT5组(M5组)、L—Arg3/MCT3组(L3组)、L-Arg5/MCT5组(L5组)。除C组外其他组大鼠均用野百合碱一次性腹腔注射诱导PH模型。此后L3组和L5组分别连续每天腹腔注射L—Arg3周和5周,M3组和M5组分别连续每天腹腔注射与L—Arg等量的生理盐水3周和5周,C组连续每天腹腔注射与L—Arg等量的生理盐水共5周。实验周期结束则用右心导管法测定右心室收缩压(RVSP),间接反映肺动脉压力,然后取大鼠肺组织做免疫组化,检测各组iNOS、内皮一氧化氮合酶(eNOS)和弹性蛋白(elastin)的表达变化。结果M3和M5组中iNOS和elastin的表达明显高于C组,而eNOS表达明显少于C组;L3和L5组iNOS和elastin的表达少于相应M3和M5组,但L5组两种蛋白表达仍高于C组,L3和L5组eNOS的减少明显比相应M3和M5组少,但不及C组。结论PH形成的中、晚期,肺组织中eNOS表达减少,而此时iNOS的表达增高可能产生大量一氧化氮(NO),但并没有改善PH的病情,而L-Arg能够恢复eNOS和iNOS之间的平衡并有效抑制PH的进展。 Objective To investigate the role of iNOS in the middle and late stage of pulmonary hypertension (PH) and the effect of L-Arginine(L-Arg) on these stage. Methods Thirty healthy male SD rats were randomly divided into five groups. All rats except those in control group were injected intraperitoneally (ip) with a single dose (50 mg/kg) of MCT to induce PH. Then the L3 and L5 groups were injected ip with 500 mg/kg L-Arg daily for3 weeks and 5weeks respectively, the M3 and M5 groups received a daily ip injection of the same amount of saline as L-Arg for 3 weeks and 5 weeks respectively; the same amount of saline was injected ip daily in control group for 5 weeks. Right ventricular systolic pressure(RVSP) was measured before lungs were excised for immunohistochemistry at the end of experiments. Results The expressions of iNOS and elastin in M3 and M5 were higher compared to the control group, but L-Arg partly reduced the expressions of iNOS and elastin both at 3 weeks and 5 weeks post-MCT. The reduction of eNOS expression in L3 and L5 groups were lower compared to M3 and M5 groups, hut the eNOS expression in L3 and L5 groups were still lower than control group. Conclusion During the middle and late stage of PH, the expression of eNOS was decreased. The expression of iNOS was induced, which would produce numerous NO. However, these NO had no benefit on the development of PH. L-Arg could restore the balance of eNOS and iNOS, and could inhibit the development of PH, which mac provide a new clues to exolore the oathogenesis and treatment of PH.
出处 《中华胸心血管外科杂志》 CSCD 北大核心 2012年第4期237-240,共4页 Chinese Journal of Thoracic and Cardiovascular Surgery
基金 2009年度科技部973项目(2009CB522104) 国家自然科学基金项目(30971261)
关键词 高血压 肺性 一氧化氮合酶 弹性蛋白 野百合碱 左旋精氨酸 Hypertension, pulmonary Nitric Oxide Synthase Elastin Monocrotaline L-arginine
  • 相关文献

参考文献13

  • 1Konduri GG, Ou J, Shi Y, et al. Decreased association of I-ISP90 impairs endothelial nitric oxide synthase in fetal lambs with persistent pulmonary hypertension. Am J Physiol Heart Circ Physiol, 2003, 285 : I-I204-H211.
  • 2Ou ZJ, Wei W, Huang DD, et al. L-arginine restores endothelial ni- tric oxide synthase-coupled activity and attenuates monocrotaline-in- duced pulmonary artery hypertension in rats. Am J Physial Endocri- nol Metab ,2010,298 : E1131 -El 139.
  • 3魏玮,区景松,黄达德,罗炜,罗兆榴,欧志君,陈文广,邓卫兵.左旋精氨酸恢复肺动脉高压一氧化氮和氧自由基的平衡[J].中山大学学报(医学科学版),2009,30(1):43-46. 被引量:4
  • 4]MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Ann Rev Immunol,1997, 15:323-350.
  • 5Kobzik L, Bredt DS, Lowenstein C J, et al. Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localiza- tion. Am J Respir Cell-Nol Biol, 1993,9:371-377.
  • 6] Eddahibi S, Adnot S, Carville C, et al. L-arginine restores endothe- lium-dependent relaxation in pulmonary circulation of chronically hy- poxic rats. Am J Physiol, 1992,263 : L194-L200.
  • 7Nagaya N, Uematsu M, Oya H, et al. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in pa-tients with precapillary pulmonary hypertension. Am J Respir Crit Care Med ,2001,163:887-891.
  • 8Fagan KA, Tyler RC, Sato K, et al. Relative contributions of endo- thelial, inducible, and neuronal NOS to tone in the murine pulmona- ry circulation. Am J Physiol, 1999,277(3 Pt 1 ) : L472-478.
  • 9Lorsbach RB, Russell SW. A specific sequence of stimulation is re- quired to induce synthesis of the antimicrobial molecule nitric oxide by mouse macrophages. Infect Immun, 1992,60:2133-2135.
  • 10Liew FY, MiUott S, Parkinson C, et al. Macrophages killing of leishmania parasite in vivo is mediated by nitric oxide from L-argi- nine. J Immunol,1990 ,144 :4794-4797.

二级参考文献12

  • 1区景松,Kirkwood A.PRITCHARD Jr.热休克蛋白90调节内皮一氧化氮合酶(一个新近认识的心血管疾病调节物)(英文)[J].中山大学学报(医学科学版),2004,25(6):493-495. 被引量:2
  • 2孙新,苏慧,臧益民,王跃民,毕辉,郭海涛,槐勇,裴建明.U50488H对低氧性肺动脉高压大鼠体内一氧化氮、内皮素及血管紧张素Ⅱ水平的影响[J].心脏杂志,2007,19(3):249-251. 被引量:18
  • 3Nagaya N, Uematsu M, Oya H, et al. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with pre-capillary pulmonary hypertension [J]. Am J Respir Crit Care Med, 2001,163(4) :887-891.
  • 4Sud N, Sharma S, Wiseman DA, et al. Nitric oxide and superoxide generation from endothelial NOS: modulation by HSP90 [J]. Am J Physiol Lung Cell Mol Physiol, 2007,293 (6) : L1444-L14453.
  • 5Pritchard KA Jr, Ackerman AW, Gross ER, et al. Heat shock protein 90 mediates the balance of nitric oxide and superoxide anion from endothelial nitricoxide synthase [J]. J Biol Chem, 2001,276(21): 17621 - 17624.
  • 6Stepp DW, Ou J, Ackerman AW, et al. Native LDL and minimally oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ [J]. Am J Physiol Heart Circ Physiol, 2002,283 (2): H750-H759.
  • 7Hampl V, Herget J. Role of nitric oxide in the pathogenesis of chronic puhnonary hypertension [J]. Physiol Rev, 2000,80(4) : 1337-1372.
  • 8Schulz E, Anter E, Keaney JF Jr. Oxidative stress, antioxidants, and endothelial function [J]. Curr Med Chem, 2004,11(9) : 1093-1104.
  • 9Konduri GG, Bakhutashvili I, Eis A, et al. Oxidant stress from uncoupled nitric oxide synthase impairs vasodilation in fetal Jambs with persistent pulmonary hypertension [J]. Am J Physiol Heart Cite Physiol, 2007,292(4) :H1812-H1820.
  • 10Chandrasekar I, Eis A, Konduri GG. Betamethasone attenuates oxidant stress in endothelial cells from fetal lambs with persistent pulmonary hypertension [J]. Pediatr Res, 2008, 63 ( 1 ) : 67-72.

共引文献3

同被引文献52

引证文献10

二级引证文献12

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部