【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-Ala²,N-Me-Phe⁴,Gly⁵-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^-1NaCl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。更多还原

【Abstract】 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（ Ce A）,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-ol]-enkephalin（ DAMGO） 0. 25 μL · nmol^-1 and losartan 5 nL·nmol^-1 into the Ce A,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 Ce A injections,non-cumulative 0. 3 mol·L^-1 NaCl 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 rehydration,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 NaCl intake and water intake in the experimental group increased significantly（ both P < 0. 05）. Compared with the experimental group,both the cumulative total NaCl 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 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（ 4. 36 ± 0. 16）,（ 9. 42 ± 2. 02）,（ 2. 81 ± 0. 76）,（ 5. 48 ± 1. 56）mL,respectively; the cumulative total water intake were（ 8. 38 ± 0. 73）,（ 12. 20 ± 1. 28）,（ 7. 05 ± 0. 52）,（ 9. 42 ± 1. 24） mL,respectively. Compared with the blank group,both the cumulative total NaCl intake and water intake in the experimental group increased significantly（ both P < 0. 05）. Compared with the experimental group,both the cumulative total NaCl intake and water intake in the combination group decreased significantly（ both P < 0. 05）.ConclusionLosartan in the brain may decrease the expression of sodium appetite mediated by μ-opioid receptor system within the Ce A,and then inhibits high sodium consumption by sodium-depleted rats.更多还原