The timing of propofol administration affects the effectiveness of remote ischemic preconditioning induced cardioprotection in rats
The timing of propofol administration affects the effectiveness of remote ischemic preconditioning induced cardioprotection in rats
复制标题
异丙酚给药时机影响远程缺血预处理诱导大鼠心脏保护的有效性
DOI：
10.1002/jcb.29671
复制
发表时间：
2020-02-07
影响因子：
4
通讯作者：
Lu, Yao
中科院分区：
文献类型：
--
作者：
Chen, Ke;Yu, Junma;Lu, Yao
在异丙酚维持麻醉下，远程缺血预适应（RIPC）的心脏保护作用被取消。心脏中存在瞬时受体电位香草酸 1 (TRPV1) 通道，其激活可引起心脏保护作用。因此，我们测试了麻醉异丙酚给药阶段是否干扰 RIPC 诱导的心脏保护作用，以及 RIPC 通过心脏 TRPV1 通道诱导的心脏保护作用。雄性 Sprague-Dawley 大鼠心肌缺血 30 分钟，然后再灌注 2 小时。 RIPC 包括对后肢进行 5 分钟缺血/再灌注的三个周期。 P-pre + RIPC 组在 RIPC 开始前 10 分钟开始以 12mg/kg/h 输注异丙酚，或者在进行 RIPC 时再灌注开始时心肌缺血后立即开始输注 (P-post + RIPC)。这两种异丙酚输注方案被应用于另外两个没有 RIPC 的组（P-pre 和 P-post 组）。通过三苯基四唑染色评估梗塞面积（IS）。通过Western blot和免疫荧光检测心脏TRPV1的表达。与对照组相比，RIPC显着降低了心肌IS（36.7±±3% vs 57.2±±4%；P<±.01）。当在 RIPC 之前开始使用异丙酚时，RIPC 的 IS 保护作用被完全消除。然而，心肌缺血后立即开始输注异丙酚并不影响 RIPC 诱导的心脏保护作用。 RIPC后TRPV1表达显着增加，如果在RIPC之前而非之后给予异丙酚，则异丙酚会抑制RIPC的TRPV1激活。我们的结果表明，丙泊酚给药时机对于保持 RIPC 的心脏保护作用至关重要。异丙酚可能通过心脏 TRPV1 受体取消 RIPC 诱导的心脏保护作用。
The cardioprotection of remote ischemic preconditioning (RIPC) is abolished under propofol maintained anesthesia. Transient receptor potential vanilloid 1 (TRPV1) channel is present in the heart, and its activation could induce cardioprotection. Therefore, we tested whether the anesthetic propofol administration phase interfered with the RIPC‐induced cardioprotection, and RIPC‐induced cardioprotection via the cardiac TRPV1 channel. Male Sprague‐Dawley rats were subjected to myocardial 30 minutes of ischemia followed by 2 hours of reperfusion. RIPC consisted of three cycles of 5‐minute ischemia/reperfusion applied to a hindlimb. Propofol infusion at 12 mg/kg/h was commenced either at 10 minutes before the start of RIPC in the P‐pre + RIPC group, or immediately after myocardial ischemia at the onset of reperfusion (P‐post + RIPC) while performing RIPC. These two propofol infusion regimes were applied to another two grou bs without RIPC (P‐pre and P‐post groups). Infarct size (IS) was assessed by triphenyltetrazolium staining. Heart TRPV1 expression was detected by Western blot and immunofluorescence. RIPC significantly reduced myocardial IS compared with the control group (36.7 ± 3% versus 57.2 ± 4%; P < .01). When propofol was started before RIPC, the IS sparing effect of RIPC was completely abolished. However, propofol infusion starting immediately after myocardial ischemia did not affect RIPC‐induced cardioprotection. TRPV1 expression significant increase after RIPC, then propofol inhibited the TRPV1 activation of RIPC if given before RIPC but not after. Our results suggest that the timing of propofol administration is critical to preserve the cardioprotection of RIPC. Propofol might cancel RIPC‐induced cardioprotection via the cardiac TRPV1 receptor.