氯沙坦在脑内对脱钠大鼠高盐摄入的抑制作用  

Inhibitory effect of losartan in the brain on hypertonic sodium intake by sodium-depleted rats

作　　者：闫君宝 卢敏江 胡志红 任爱红 范玲玲 邓博 杨东伟 

机构地区：[1]河南科技大学医学院生理学教研室,河南洛阳471023 [2]三门峡中心医院内分泌科,河南三门峡472000

出　　处：《中国临床药理学杂志》2017年第24期2588-2591,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河南省高等学校重点科研基金资助项目(15A180014)

摘　　要：目的研究氯沙坦对钠欲的影响作用及机制。方法给予双侧杏仁中央核插管大鼠禁水24 h后自由饮水2 h处理,或皮下联合注射呋塞米与卡托普利处理,以诱导其成为摄钠模型大鼠。给摄钠模型大鼠双侧杏仁中央核内联合注射0.9%NaCl、[D-Ala^2,N-Me-Phe^4,Gly^5-ol]-enkephalin(DAMGO)0.25μL·nmol^(-1)和氯沙坦5 nL·nmol^(-1),实验分为4组:0.9%NaCl+0.9%NaCl(空白组)、0.9%NaCl+DAMGO(实验组)、0.9%NaCl+氯沙坦(对照组)和氯沙坦+DAMGO(联合组)。用摄食-摄水-活动度分析仪分别记录摄钠模型大鼠在杏仁中央核注射后15,30,45,60,90,120,150,180,210,240 min时的0.3mol·L^(-1)NaCl和水的非累积摄入量(双瓶测试)。结果在禁水后不完全补水所诱导的摄钠模型大鼠,整个钠欲测试期(240 min)累积的总的摄钠量,空白组、实验组、对照组和联合组大鼠分别是(2.01±0.32),(8.04±1.67),(1.75±0.31),(4.26±0.60)mL,累积的总的摄水量分别是(2.66±0.66),(10.40±2.69),(2.15±0.46),(5.34±0.91)mL;与空白组相比,实验组摄钠量和摄水量都明显增加,差异均有统计学意义(均P<0.05);与实验组相比,联合组摄钠量和摄水量都显著降低,差异均有统计学意义(均P<0.05)。在皮下联合注射呋塞米与卡托普利所诱导的摄钠模型大鼠,整个钠欲测试期累积的总的摄钠量,空白组、实验组、对照组和联合组大鼠分别是(4.36±0.16),(9.42±2.02),(2.81±0.76),(5.48±1.56)mL,累积的总的摄水量分别是(8.38±0.73),(12.20±1.28),(7.05±0.52),(9.42±1.24)mL;与空白组相比,实验组摄钠量和摄水量都明显增加,差异均有统计学意义(均P<0.05);与实验组相比,联合组摄钠量和摄水量都显著降低,差异均有统计学意义(均P<0.05)。结论氯沙坦在中枢能抑制杏仁中央核μ-阿片受体系统所介导的钠欲表达,脱钠大鼠钠盐摄入减少。Objective To investigate the effect of losartan on sodium appetite and its underlying mechanisms. Methods Sprague - Dawley rats, with stainless steel cannulas implanted bilaterally into the central nucleus of amygdala （ CeA）, were treated with water deprivation for 24 h followed voluntary drinking - water for 2 h or treated with furosemide combined with captopril injected subcutaneously in order to induce to be Na ＋ ingestion models. The Na ＋ ingestion models of rat were received bilateral injections of combinations of saline, [ D -Ala2, N - Me - Phe4, Gly5 -oil -enkephalin （DAMGO） 0. 25 μL · nmol-1 and losartan 5 nL · nmol- 1 into the CeA, and the rats were randomly assigned to fourgroups ： saline ＋ saline （ blank group）, saline ＋ DAMGO （ experimental group）, losartan ＋ saline （ control group）, or losartan ＋ DAMGO （combination group）. Following the CeA injections, non- cumulative 0. 3 mol · L^-1NaCl intake and water intake were automatically recorded by feeding - drinking - activity analyser at 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min （two-bottle test）. Results In rats treated with water deprivation followed partial rehy- dration, over the entire 240 min sodium appetite tests, the cumulative total 0. 3 mol · L-1 NaCl intake in blank group, experimental group, control group, and combination group were （ 2.01 ± 0. 32 ）, （ 8.04 ± 1.67 ）, （ 1.75 ± 0. 31 ）, （4.26 ± 0. 60 ） mL, respectively; the cumulative total water intake were （ 2.66 ±0. 66 ）, （ 10. 40 ± 2. 69 ）, （2. 15 ±0. 46）,（5.34 ± 0. 91 ）mL, respectively. Compared with the blank group, both the cumulative total NaC1 intake and water intake in the experimental group increased significantly （ both P 〈 0. 05 ）. Compared with the experimental group, both the cumulative total NaCI intake and water intake in the combination group decreased significantly （both P 〈 0. 05 ）. In rats treated with subcutaneous injections of furosemide combined with captopril, over

关 键 词：氯沙坦 μ-阿片受体激动药 杏仁中央核 钠欲 钠盐摄入 

分 类 号：R972.4[医药卫生—药品]