褪黑素抗心肌缺血/再灌注损伤的室旁核机制

    Mechanism of melatonin through paraventricular nucleus against myocardial ischemia/reperfusion injury

    • 摘要:
        目的  探讨外周输注褪黑素通过下丘脑室旁核(PVN)调节交感神经活性对抗心肌I/R损伤的机制。
        方法  腹腔注射褪黑素或者无菌生理盐水,24 h后建立C57BL/6J小鼠心肌I/R损伤模型。超声心动图测定心功能,用Evans blue/TTC双染色法测定再灌注24 h后心肌梗死面积。免疫荧光检测下丘脑室旁核(PVN)IL-10和IL-1β及心肌酪氨酸羟化酶(TH)水平;Western blot检测下丘脑室旁核NF-κB水平;ELISA检测血浆去甲肾上腺素(NE)水平。
        结果  外周给予褪黑素可抑制PVN区NF-κB水平(P<0.01),进而降低PVN区IL-1β水平(P<0.01),升高IL-10水平(P<0.01),降低NE及TH活性,缩小心肌梗死面积(P<0.01),改善C57BL/6J小鼠心功能。
        结论  外周注射褪黑素,通过调控PVN区炎性细胞因子水平,抑制交感神经活性,改善心肌I/R损伤所致心功能降低。

       

      Abstract:
        AIM  To explore the mechanism of peripheral injection of melatonin in regulating sympathetic activity through hypothalamic paraventricular nucleus (PVN) against myocardial I/R injury.
        METHODS  The myocardial I/R injury model of C57BL/6J MICE was established 24 hours after intraperitoneal injection of melatonin or sterile saline. T cardiac functions were measured by echocardiography and the infarct size was measured by Evans blue/TTC double staining after 24 hours of reperfusion. The levels of Il-10 and il-1β in paraventricular nucleus of hypothalamus were detected by immunofluorescence assay, the levels of NF-κb in paraventricular nucleus of hypothalamus and myocardial Tyrosine 3-monooxygenase were detected by Western blot and the level of (-)-noradrenaline in plasma was detected by ELISA.
        RESULTS  Peripheral administration of melatonin inhibited NF-ΚB level in PVN region, decreased IL-1 β level in PVN region, increased IL-10 level, decreased NE and TH activity, reduced infarct size (all P<0.01) and improved cardiac functions in C57BL/6J mice.
        CONCLUSION  Peripheral injection of melatonin can regulate the level of inflammatory cytokines in PVN, inhibit the activity of sympathetic nervous system and improve the cardiac function decline induced by myocardial I/R injury.

       

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