■右美托咪定(Dex)是一种有效的α2-肾上腺素能受体(α2-AR)激动剂,已被证明可以预防脓毒症引起的肺损伤,然而,这种保护的潜在机制尚未完全理解。自噬和Smad2/3信号通路在脓毒症肺损伤中发挥重要作用,但是Dex和Smad2/3之间的关系并不清楚。本研究旨在探讨自噬和Smad2/3信号通路在Dex介导脓毒症肺损伤治疗中的作用。在C57BL/6J小鼠中使用盲肠结扎和穿孔(CLP)进行脓毒症。
■将小鼠随机分为四组(每组n=6):假手术,CLP,CLP-Dex,和CLP-Dex-YOH,盐酸育亨宾(YOH)是α2-AR阻断剂。小心地分离盲肠以避免血管损伤,并用18号针进行鉴定和穿刺两次。病理变化,炎症因子水平,氧化应激,自噬,肺组织中Smad2/3信号通路相关蛋白水平,测定血清超氧化物歧化酶(SOD)和丙二醛(MDA)活性。
■CLP诱导的肺损伤反映在炎性细胞因子水平的升高,凋亡,和氧化应激,自噬和Smad2/3信号通路相关蛋白的表达增加。Dex可以逆转这些变化,并在脓毒症期间对肺产生保护作用。然而,YOH的给药显著降低了Dex对脓毒症小鼠的积极作用。
■Dex通过调节自噬和Smad2/3信号通路发挥对脓毒症肺损伤的有益作用。
UNASSIGNED: Dexmedetomidine (Dex) is a potent α2-adrenergic receptor(α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. Autophagy and the Smad2/3 signaling pathway play important roles in sepsis-induced lung injury, but the relationship between Dex and Smad2/3 is not clear. This study aimed to investigate the role of autophagy and the Smad2/3 signaling pathway in Dex-mediated treatment of sepsis-induced lung injury. Sepsis was performed using cecal ligation and puncture (CLP) in C57BL/6J mice.
UNASSIGNED: Mice were randomly assigned to four groups (n=6 per group): sham, CLP, CLP-Dex, and CLP-Dex-YOH, Yohimbine hydrochloride (YOH) is an α2-AR blocker. The cecum was carefully separated to avoid blood vessel damage and was identified and punctured twice with an 18-gauge needle. The pathological changes, inflammatory factor levels, oxidative stress, autophagy, Smad2/3 signaling pathway-related protein levels in lung tissues, and the activity of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum were measured.
UNASSIGNED: CLP-induced lung injury was reflected by increased levels of inflammatory cytokines, apoptosis, and oxidative stress, along with an increase in the expression of autophagy and Smad2/3 signaling pathway-related proteins. Dex could reverse these changes and confer a protective effect on the lung during sepsis. However, the administration of YOH significantly reduced the positive effects of Dex in mice with sepsis.
UNASSIGNED: Dex exerts its beneficial effects against sepsis-induced lung injury through the regulation of autophagy and the Smad2/3 signaling pathway.