右美托咪啶通过抑制肺成纤维细胞缝隙连接功能，保护脂多糖诱导的细胞凋亡
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The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts
背景与目的
α2-肾上腺素受体激动剂右美托咪定对急性肺损伤（ALI）具有保护作用，但其机制还有很多尚不清楚。
方 法
本研究探讨人肺成纤维细胞株中，右美托咪定对脂多糖（LPS)）诱导的细胞凋亡的影响以及此效应与缝隙连接细胞间通讯的关系。采用流式细胞术检测LPS诱导的细胞凋亡，细胞接种荧光法测定缝隙连接功能，western blot检测缝隙连接蛋白43(Cx 43)的表达水平。
结 果
结果表明，人肺成纤维细胞在LPS作用24h后，细胞凋亡增加，而右美托咪啶和18α-GA预处理可显著降低LPS诱导的细胞凋亡。右美托咪啶作用1h后主要通过降低人肺成纤维细胞Cx 43蛋白水平而抑制缝隙连接功能。这些结果表明，右美托咪啶对缝隙连接细胞间通讯的抑制通过降低cx 43蛋白水平而抑制缝隙连接功能，从而影响LPS诱导的细胞凋亡。
结 论
本研究为揭示麻醉药物在ALI中保护作用的新机制提供了证据。
原始文献摘要
Zhang Y, Tan X, Xue L.Biochem Biophys Res Commun. 2018 Jan 1;495(1):92-97. doi: 10.1016/j.bbrc.2017.10.162. Epub 2017 Oct 31.
The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43). The results revealed that exposure of human lung fibroblast cell line to LPS for 24 h increased the apoptosis, and pretreatment of dexmedetomidine and 18α-GA significantly reduced LPS-induced apoptosis. Dexmedetomidine exposure for 1 h inhibited gap junction function mainly via a decrease in Cx43 protein levels in human lung fibroblast cell line. These results demonstrated that the inhibition of gap junction intercellular communication by dexmedetomidine affected the LPS-induced apoptosis through inhibition of gap junction function by reducing Cx43 protein levels. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting ALI.
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