Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells
Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells
复制标题
右美托咪定通过抑制血管内皮细胞上的 Connexin43 减弱单核细胞内皮粘附
DOI：
10.1155/2020/7039854
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发表时间：
2020-02-10
影响因子：
4.6
通讯作者：
Chen, Jimei
中科院分区：
文献类型：
--
作者：
Chai, Yunfei;Yu, Runying;Chen, Jimei
目前的研究已经确定了右美托咪定对多个器官的多方面保护功能。我们首次阐明了右美托咪定对单核细胞内皮粘附的影响及其潜在机制是否与调节单核细胞内皮粘附的关键因子连接蛋白43（Cx43）有关。 U937 单核细胞和人脐静脉内皮细胞 (HUVEC) 用于探索单核细胞-内皮粘附。设计了两种特殊的 siRNA 来抑制 HUVEC 上的 Cx43 表达。检测U937-HUVEC粘附、粘附相关分子以及MAPK（p-ERK1/2、p-p38和p-JNK1/2）信号通路的激活。右美托咪定以其临床相关浓度（0.1nM 和 1nM）作为 HUVEC 的预处理。还研究了其对 Cx43 和 U937-HUVEC 粘附的影响。结果表明，抑制 HUVEC 上的 Cx43 可以减弱 MCP-1、可溶性 ICAM-1 (sICAM-1)、可溶性 VCAM-1 (sVCAM-1) 以及粘附分子 ICAM-1 和 VCAM-1 的未加工变体的含量，最终导致 U937-HUVEC 粘附力降低。同时，MAPKs的激活也受到抑制。 U0126（抑制p-ERK1/2）和SB202190（抑制p38）降低了MCP-1、sICAM-1和sVCAM-1的含量，但SP600125（抑制p-JNK1/2）没有这些作用。 ICAM-1 和 VCAM-1 可以以类似的方式进行调节。右美托咪定预处理抑制 HUVEC 上的 Cx43、MAPK 的激活和 U937-HUVEC 粘附。因此，我们得出结论，右美托咪定通过抑制 HUVEC 上的 Cx43 调节 MAPK 信号通路的激活来减弱 U937-HUVEC 粘附。
Current studies have identified the multifaceted protective functions of dexmedetomidine on multiple organs. For the first time, we clarify effects of dexmedetomidine on monocyte-endothelial adherence and whether its underlying mechanism is relative to connexin43 (Cx43), a key factor regulating monocyte-endothelial adherence. U937 monocytes and human umbilical vein endothelial cells (HUVECs) were used to explore monocyte-endothelial adherence. Two special siRNAs were designed to knock down Cx43 expression on HUVECs. U937-HUVEC adhesion, adhesion-related molecules, and the activation of the MAPK (p-ERK1/2, p-p38, and p-JNK1/2) signaling pathway were detected. Dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), was given as pretreatments to HUVECs. Its effects on Cx43 and U937-HUVEC adhesion were also investigated. The results show that inhibiting Cx43 on HUVECs could attenuate the contents of MCP-1, soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1), and the nonprocessed variants of the adhesion molecules ICAM-1 and VCAM-1 and ultimately result in U937-HUVEC adhesion decrease. Meanwhile, the activation of MAPKs was also inhibited. U0126 (inhibiting p-ERK1/2) and SB202190 (inhibiting p38) decreased the contents of MCP-1, sICAM-1, and sVCAM-1, but SP600125 (inhibiting p-JNK1/2) had none of these effects. ICAM-1 and VCAM-1 could be regulated in a similar way. Dexmedetomidine pretreatment inhibited Cx43 on HUVECs, the activation of MAPKs, and U937-HUVEC adhesion. Therefore, we conclude that dexmedetomidine attenuates U937-HUVEC adhesion via inhibiting Cx43 on HUVECs modulating the activation of MAPK signaling pathways.