褪黑素在有氧运动改善自发性高血压大鼠血压和肠系膜动脉功能中的作用
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国家自然科学基金(31371201);北京市自然科学基金(5132017);新世纪优秀人才支持计划(NCET-11-0850)


The Role of Melatonin in the Improvement of Blood Pressure and Mesenteric Artery Function Induced by Aerobic Exercise in Spontaneously Hypertensive Rats
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    目的 探讨褪黑素在有氧运动改善自发性高血压大鼠(SHR)血压和肠系膜动脉功能中的作用。方法 选用12周龄雄性SHR 54只和Wistar-Kyoto(WKY)大鼠(WKY组,即正常血压对照组)18只。SHR随机分为5个组,即安静空白对照组(SHR-SED组,n=18)、安静生理盐水注射组(SHR-SED+NS组,n=6)、安静褪黑素受体阻断剂2-苯基-N-乙酰色胺(Luz)[1 mg/(kg·d)]注射组(SHR-SED+Luz组,n=6)、有氧运动组(SHR-EX组,n=18)、有氧运动Luz注射组(SHR-EX+Luz组,n=6)。运动组进行8周有氧训练:坡度0°,18~20 m/min,每天60 min,每周5天。8周有氧运动后,采用尾动脉无创法测量大鼠血压与心率;WKY组、SHR-SED组、SHR-EX组采用ELISA竞争法测定血清褪黑素水平;离体微血管环实验测定二、三级肠系膜动脉的舒缩特性。结果 (1)8周有氧运动后,SHR-EX组的收缩压、舒张压、平均动脉压和心率与SHR-SED组相比显著降低。SHR-EX+Luz组的收缩压、心率明显高于SHR-EX组,却低于SHR-SED+Luz组;而SHR-SED组与SHR-SED+NS组、SHR-SED+Luz组比较无差异。(2)WKY组和SHR-SED组血清褪黑素浓度在21∶00~22∶00时最高,明显高于12∶00~13∶00和8∶00~9∶00;但SHR-EX组在8∶00~9∶00最高。在3个时间段内,WKY组血清褪黑素浓度始终显著高于SHR-SED组;但在8∶00~9∶00时间段,SHR-EX组明显高于WKY组、SHR-SED组。(3)微血管环在去甲肾上腺素(10-5 mol/L)预收缩后,对褪黑素(10-6~10-3 mol/L)呈浓度依赖性舒张反应,pIC50值:WKY组>SHR-EX组>SHR-SED组,且各组无Nω-硝基-L-精氨酸甲酯的内皮完整血管舒张幅度大于有Nω-硝基-L-精氨酸甲酯(10-4 mol/L)的内皮不完整血管;Luz(2×10-6 mol/L)预孵育微血管环20 min,可部分阻断褪黑素的舒张作用。结论 有氧运动可降低SHR的收缩压和心率,增强肠系膜动脉舒张作用,其中褪黑素发挥了重要作用。

    Abstract:

    Aim To investigate the role of melatonin in the improvement of blood pressure and mesenteric arterial function induced by aerobic exercise in spontaneously hypertensive rat (SHR). Methods A total of 72 twelve-week-old male rats were used in the experiments. A group of normotensive WKY rats (n=18) was used as normal blood pressure control group (WKY group). 54 SHRs were separated into five groups: SHR sedentary control group (SHR-SED, n=18), SHR sedentary with normal saline injection group (SHR-SED+NS, n=6), SHR sedentary with melatonin receptor blocker luzindole (Luz) injection group (SHR-SED+Luz, n=6), SHR aerobic exercise group (SHR-EX, n=18), and SHR aerobic exercise with Luz injection group (SHR-EX+Luz, n=6). Luz was injected 1 mg/(kg·d) intraperitoneally. Rats in the aerobic exercise groups were subjected with 8 weeks-treadmill exercise: 0° slope, 18~20 m/min, 60 min each day, 5 days each week. Blood pressure and heart rate (HR) of awake animals were measured by using tail-cuff method before the beginning of the exercise training protocol and at the end of the protocol. Serum melatonin level was examined by ELISA with commercially available kits. The mechanical properties of small mesenteric arteries were studied with vascular ring experiment in vitro. Results (1)After exercise training for 8 weeks, systolic blood pressure (SBP), diastolic blood pressure, mean arterial pressure and HR were significantly lower in SHR-EX group than those in SHR-SED group. SBP and HR in SHR-EX+Luz group were greater compared to SHR-EX group. However, there were no significant differences of SBP and HR between SHR-SED group and SHR-SED+NS group, SHR-SED+Luz group. (2)The serum melatonin levels in WKY group and SHR-SED group reached peak level at 21∶00~22∶00, and were significantly higher than those at 12∶00~13∶00 and 8∶00~9∶00. However, it reached the peak level at 8∶00~9∶00 in SHR-EX group. In these three time periods of day, serum melatonin concentration in WKY group was always significantly higher than that in SHR-SED group But it was significantly higher at 8∶00~9∶00 in SHR-EX group than those in WKY group and SHR-SED group. (3)Melatonin (10-6~10-3 mol/L) caused a concentration-dependent relaxation in small mesenteric arterial beds precontracted by norepinephrine (10-5 mol/L), with pIC50 value∶ WKY group>SHR-EX group>SHR-SED group. In the presence of L-nitro-arginine-methyl ester (L-NAME) (eNOS inhibitor), the pIC50 of the concentration-response curve for melatonin-induced relaxation was lower than that in the absence of L-NAME in both SHR and WKY rats. The relaxation of melatonin was partly blocked by Luz (2×10-6 mol/L). Conclusion Aerobic exercise can reduce SBP and HR of SHR, and enhance mesenteric artery vasodilation, in which melatonin plays an important role.

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邱 方,熊开宇,石丽君.褪黑素在有氧运动改善自发性高血压大鼠血压和肠系膜动脉功能中的作用[J].中国动脉硬化杂志,2015,23(12):1229~1235.

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  • 收稿日期:2015-01-04
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  • 在线发布日期: 2015-12-26