七氟醚对单肺通气大鼠肺癌HIF-1α/EMT通路活性及侵袭力的影响

Effects of sevoflurane on HIF-1α/EMT pathway activity and invasion of lung cancer in rats undergoing one lung ventilation

目的观察七氟醚对单肺通气(OLV)大鼠肺癌缺氧诱导因子1α(HIF-1α)/上皮间质转化(EMT)通路和侵袭力的影响。方法建立大鼠肺癌模型。将造模大鼠随机分为4组(n=6):对照组(C组)、双肺通气组(T组)、单肺通气组(O组)和七氟醚+单肺通气组(SO组)。T组气管插管后行双肺通气2.5 h;O组和SO组气管插管后行OLV 2 h,双肺通气0.5 h。SO组OLV期间维持呼气末七氟醚浓度2.6%(相当于人1.5 MAC),双肺通气0.5 h时处死大鼠取左肺组织,Western blot测定肺癌组织低氧诱导因子(HIF)-1α、波形蛋白(Vimentin)、纤连蛋白(Fibronectin)表达水平。RT-PCR检测肺癌组织基质金属蛋白酶(MMP)-2和MMP-9表达。结果与C组和T组比较,O组和SO组HIF-1α、Vimentin、Fibronectin蛋白表达水平升高,MMP-2和MMP-9 m RNA表达上调;与O组比较,SO组HIF-1α、Vimentin、Fibronectin蛋白表达水平下调,MMP-2和MMP-9 m RNA表达下调(P<0.05)。结论七氟醚抑制OLV上调大鼠肺癌HIF-1α/EMT通路活性及侵袭力的作用。

Objective To investigate the effects of sevoflurane on HIF-1α/epithelial mesenchymal transition（EMT）pathway activity and invasion of lung cancer in rats undergoing one lung ventilation（OLV）. Methods Lung cancer model of SD rats was established. Rats were randomly divided into 4 groups：group control（group C）,group two lungs ventilation（TLV）（group T）,group one lungs ventilation（group O）,and group sevoflurane ＋one lungs ventilation（group SO）. Two lung ventilation was performed after endotracheal intubation for 2.5 h ingroup T. OLV was performed after endotracheal intubation for 2 h in group O and SO. The end-expiratory concentrationof sevoflurane of rats in group SO was maintained 2.6% during OLV period. Left lung cancer tissues were harvestedat 0.5 h of TLV. The protein levels of HIF-1α,Vimentin and Fibronectin in lung cancer were determined by Westernblot. The m RNA levels of MMP-2 and MMP-9 in lung cancer were evaluated by RT-PCR. Results The expres-sions of HIF-1α,Vimentin,Fibronectin,MMP-2,and MMP-9 in group O and group SO were significantly higherthan those in group C and group T（P〈0.05）. The expressions of HIF-1α,Vimentin,Fibronectin,MMP-2,andMMP-9 were decreased significantly in group SO as compared with group O（P〈0.05）. Conclusion Sevofluraneinhibits the elevation of HIF-1α/EMT pathway activity and invasion ability induced by OLV.