硝基精氨酸赖氨酸三肽对感染性休克大鼠血压的影响并机制探讨  

Effects of N G nitro Arginine Lysine tripeptide on the blood pressure of septic shock and study of its mechanism in rats

作　　者：杨军珂[1] 孟素荣[1] 吴赛珠[1] 周可祥[1] 彭师奇[2] 吴宗贵[3] 阮云军[1,4] 

机构地区：[1]第一军医大学南方医院心内科,广州510515 [2]北京医科大学中德联合实验室 [3]第二军医大学长征医院心内科 [4]彭师奇

出　　处：《急诊医学》2000年第5期298-301,共4页

基　　金：国家新药研究与开发基金资助! (编号 :96 90 1 0 5 4 4)

摘　　要：目的　用合成的硝基精氨酸 赖氨酸三肽 (以下简称新化合物 )在大鼠感染性休克模型上检测其对血压的影响 ,并对其作用机制作一探讨。方法 :1.盲肠结扎穿孔法 (CLP)建立大鼠感染性休克模型 ,检测新化合物对血压、血清一氧化氮 (NO)的影响。 2 .大鼠腹腔巨噬细胞培养 ,检测新化合物对诱导型一氧化氮合酶 (iNOS)的抑制程度。 3 .大鼠离体主动脉条孵育 ,检测新化合物对结构型一氧化氮合酶 (cNOS)的抑制程度。结果 :1.新化合物 ( 0 0 1mmol/kg)明显升高感染性休克大鼠血压至接近假手术组水平 ;注射新化合物、NG- 硝基 左旋精氨酸(L NNA)可使大鼠血清NO水平下降 ,新化合物较L NNA作用更明显。 2 .新化合物 ( 10 4mol/L)可显著抑制大鼠腹腔巨噬细胞产生NO (P <0 0 1) ,较L NNA作用增强 (P <0 0 1)。 3 .与L NNA相比 ,新化合物 ( 1 5× 10 4mol/L)对大鼠主动脉壁cNOS的抑制程度减小 (P <0 0 5)。结论 :硝基精氨酸 赖氨酸三肽对感染性休克大鼠血压有优越的升高作用 ,其机制在于选择性地抑制iNObjective:We study the effects of a new synthetic N G nitro Arginine Lysine tripeptide on septic shock.We also study its inhibition mechanisms Methods:1)Rat septic shock model was established by cecal ligation and puncture(CLP),the effects of the new synthetic peptide on the blood pressure and plasma nitric oxide(NO)level were studied.2)Rat peritoneal macrophages were cultuved to test the inhibitory role of the new synthetic peptide on inducible nitric oxide synthase(iNOS).3)Isolated rat aortic slices were incubated to test the inhibitory role of the new synthetic on constitetive nitric oxide synthase(cNOS).Results:1)Infusion of the new synthetic(0 01mmol/kg)could elevate the blood pressure of the septic shock rats nearly to the level of the sham operated rats;Infusion of both the new synthetic and N G nitro Larginine(L NNA) could decrease the plasma NO level of the septic shock rats,the former is more potent.2)The new synthetic(10 4 mmol/L)could significantly inhibit rat peritoneal macrophages to produce NO(P<0 01),and had more potency than L NNA(P<0 01).3)The new synthetic(1 5×10 4 mol/L)had less inhibitory role on cNOS of rat aorta,compared with L NNA(P<0 05).Conclusion:Due to its selected inhibitory role to iNOS,N G - nitro Arginine Lysine tripeptide has a superior elevated result on blood pressure of septic shock rats.

关 键 词：感染性休克 大鼠 硝基精氨酸-赖氨酸三肽 血压 

分 类 号：R96[医药卫生—药理学]