神经降压素受体1在大鼠肺缺血再灌注损伤中的表达及作用

Effect of NTR1 expression in rats with lung ischemia-reperfusion injury and mechanism

目的观察神经降压素受体1(NTR1)在大鼠肺缺血再灌注损伤LIRI模型中的表达和作用及其与Toll样受体4(TLR4)和缺氧诱导因子(HIF-1α)的关系,探讨NTR1在LIRI中的病理作用机制。方法 40只雄性SD大鼠,分为8组进行观察。1假手术组;2LIRI组;3LIRI+生理盐水对照组;4LIRI+DMSO对照组;5LIRI+脂多糖干预组(TLR4激活组);6LIRI+TAK-242干预组(TLR4抑制组);7LIRI+NT干预组(NTR1激活组);8LIRI+SR48692干预组(NTR1抑制组)。制作大鼠原位LIRI模型,取各组大鼠左肺组织,观察肺组织病理变化、行逆转录-聚合酶链反应(RT-PCR)及蛋白质印迹法检测,统计分析NTR1在大鼠LIRI模型中的表达及作用及其与TLR4和HIF-1α的关系。结果肺IRI组NTR1 mRNA及蛋白的表达较假手术组增加(P<0.05);NT可进一步增加LIRI的炎症因子水平、细胞凋亡及肺组织病理损伤,而SR48692可减轻上述改变(P<0.05);与LIRI组比较,脂多糖干预组NTR1表达进一步增强,而TAK-242干预组NTR1表达则受到抑制(P<0.05);与LIRI组比较,HIF-1α mRNA和蛋白表达被SR48692抑制,而被NT增强(P<0.05)。结论NT-NTR1与LIRI关系密切,参与了LIRI的发病机制,在LIRI中,可能存在TLR4-NTR1-HIF-1α信号通路,本研究为发现新的LIRI有效治疗靶点提供了理论依据。

Objective To investigate neurotensin receptor 1 （NTR1） expression and the effect and mechanism of NTR1 expression in rats with lung ischemia-reperfusion injury （LIRI）. Methods Forty SD rats were randomly grouped as Sham group, LIRI group, LIRI＋saline control group, LIRI＋DMSO control group, LIRI＋TLR4-activated group, LIRI＋TAK-242 group （TLR4-inhibited group）, LIRI＋NTR1-activated group and LIRI＋ NTR1-inhibited group. The NTR1 expression and the role of NTR1 in the LIRI rats were detected with RT-PCR and Western blot and statistically analyzed. Results NTR1 mRNA and protein expressions in the LIRI group were significantly increased comparing with the sham group （ P〈0.05）. NT further increased the levels of inflammatory cytokines, apoptosis and lung pathological injury in the LIRI group, while SR48692 significantly reduced the above changes （ P〈 0.05）. Compared with the LIRI group, NTR1 expression was further enhanced in the LIRI＋LPS group and was significantly inhibited in the LIRI＋TAK-242 group （ P〈0.05）. HIF-1αmRNA and protein expressions were significantly inhibitedby SR48692 and was significantly enhanced by NT compared with the LIRI group（ P〈0.05）. Conclusions There is a close relationship between NTR1 and LIRI. NT-NTR1 is involved in the pathogenesis of LIRI. There may be TLR4-NTR1-HIF-1α signal pathway in LIRI and the theoretical basis is provided to find new effective therapeutic targets in LIRI.