关键词: 肺缺血/再灌注损伤, 蛋白激酶D2, HIF-1 α/VEGFA信号通路, 2-甲氧基雌二醇

Abstract: Objective To observe the effect of up-regulation of protein kinase D2 (PKD2) expression on lung ischemia-reperfusion injury (LI/RI) in mice. Methods 20 C57BL/6J wild-type (WT) mice and 40 PKD2 over-expression (PKD2^+/+) mice were randomly divided into sham operation group (WS and PS groups), LI/RI group (WIR and PIR groups, the left hilum was first clamped for 1 h, then reperfused for 2 h) and the hypoxia inducible factor-1α (HIF-1α) inhibitor (2-methoxyestradiol, 2-ME) group (WIR+2ME) and (PIR+2ME) groups, 20 mg/(kg·d) 2ME was injected intraperitoneally 2 days before modeling). After 2 hours of reperfusion, the wet/dry weight ratio(W/D) of lung tissues was detected, the pathological changes of lung tissues were observed by HE staining, and the content of inflammatory factors TNF-α, IL-1β and IL-6 in lung tissues were detected by ELISA. RT-qPCR and Western blot were used to detect the expression of (HIF-1α) and vascular endothelial growth factor A(VEGFA) mRNA and protein in lung tissues. Results Compared with WS group, the W/D value of the WIR group increased, the lung tissues were damaged, the content of inflammatory factors increased, and the expression of HIF-1α and VEGFA mRNA and protein increased (P＜0.05). Compared with the WIR group, the PIR group W/D value decreased, lung tissue damage was reduced, inflammatory factor content decreased, HIF-1α and VEGFA mRNA and protein expression increased (P＜0.05). Compared with WIR and PIR groups, W/D values of (WIR+2ME) and (PIR+2ME) groups increased, lung tissue damage worsened, inflammatory factor content increased, HIF-1α and VEGFA mRNA and protein expression significantly decreased (P＜0.05). Conclusions Up-regulation of PKD2 expression can improve LI/RI, and its mechanism may be related to increasing the expression of HIF-1α/VEGFA signaling pathway.

Key words: lung ischemia-reperfusion injury, protein kinase D2, HIF-1 α/VEGFA signaling pathway, 2-methoxyestradiol