右美托咪啶对高血压性肥厚心肌缺血再灌注损伤的心肌保护作用
本公众号每天分享一篇最新一期Anesthesia & Analgesia等SCI杂志的摘要翻译，敬请关注并提出宝贵意见
Dexmedetomidine Maintains Its Direct Cardioprotective Effect Against Ischemia/Reperfusion Injury in Hypertensive Hypertrophied Myocardium
背景与目的
右美托咪啶(Dex) 作用于α2-肾上腺能受体(α2-AR) 通过内皮型一氧化氮合酶 (eNOS) 磷酸化对缺血再灌注损伤有直接的心脏保护作用。通过建立自发性高血压大鼠(SHR)和Wistar-京都(WKY)大鼠模型，观察Dex对肥厚心肌的保护作用及α2-AR和I1咪唑啉受体(I1r)在 其中的不同作用。
方 法
缺血前用或不用Dex下大鼠心脏局部缺血40分钟，再灌注120分钟。测量梗死面积并通过Western Blot检测eNOS的磷酸化水平。采用免疫组织化学、实时逆转录聚合酶链反应(RT-PCR)和WesternBlot检测受体的存在与表达。
结 果
在WKY中，Dex可显著缩小梗死范围，增加磷酸化-eNOS/eNOS比值。这些作用能被育亨宾(α2-AR拮抗剂)和依法克生(α2-AR和I1r拮抗剂)所拮抗。在SHR中，Dex明显缩小了梗死面积，此作用可被依法克生所拮抗而非育亨宾。Dex没有改变SHR中磷酸化的-eNOS /eNOS比值。 WKY和Shr心脏组织中有α2-AR和I1r的表达，虽然α2a-ar和α2b-arm RNA和蛋白质水平在SHR中上调，I1r在两物种间的表达基本一致。
结 论
尽管存在α2-AR上调，Dex以eNOS-非依赖方式通过I1r对肥厚心肌缺血再灌注损伤有直接的心脏保护作用。
原始文献摘要
Yoshikawa Y, Hirata N, Kawaguchi R, et al. Dexmedetomidine Maintains Its Direct Cardioprotective Effect Against Ischemia/Reperfusion Injury in Hypertensive Hypertrophied Myocardium[J]. Anesthesia & Analgesia, 2017:1.
BACKGROUND: Dexmedetomidine (DEX) has a direct cardioprotective effect against ischemia/reperfusion injury through endothelial nitric
oxide synthase (eNOS) phosphorylation via α2-adrenoreceptor (α2-AR). By using spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat models, the cardioprotective effect of DEX in hypertrophied myocardium and the differential characteristics of cardiac α2-AR and the I1 imidazoline receptor (I1R) were examined.
METHODS: Langendorff-perfused rat hearts underwent 40 minutes of global ischemia followed by 120 minutes of reperfusion in the presence or absence of DEX before ischemia. Infarct size was measured, and eNOS phosphorylation was assessed by Western blotting. The presence and expression of the receptors were assessed by immunohistochemistry, real-time reverse transcriptase polymerase chain reaction, and Western blotting.
RESULTS: In WKY, DEX significantly decreased infarct size and increased phosphorylated-eNOS/eNOS. These effects were counteracted by yohimbine (α2-AR antagonist) and efaroxan (α2-AR and I1R antagonist). In SHR, DEX significantly decreased infarct size, and the effect was counteracted by efaroxan but not yohimbine. DEX did not alter phosphorylated-eNOS/eNOS in SHR. α2-AR and I1R were observed in WKY and SHR hearts. Although alpha2A-AR and alpha2B-AR messenger RNA and protein levels were upregulated in SHR, I1R expression was comparable between the 2 species.
CONCLUSIONS: In the hypertrophied heart, DEX maintains its direct cardioprotective effect against ischemia/reperfusion injury via I1R in an eNOS-nondependent manner despite upregulation of α2-AR.
麻醉学文献进展分享
联系我们