七氟醚调节Nrf2/HO-1信号通路对肺结核大鼠肺组织损伤的影响

Effect of Sevoflurane on Lung Tissue Damage in Rats with Pulmonary Tuberculosis by Regulating the Nrf2/HO-1 Signaling Pathway

目的:探究七氟醚(Sevo)调节Nrf2核因子E2相关因子(Nrf2)/血红素氧化酶(HO-1)信号通路对肺结核(PTB)大鼠肺组织损伤的影响。方法:建立PTB大鼠模型。将大鼠分为Control组、Model组、七氟醚高、中、低剂量组(S-H组、S-M组、S-L组)、高剂量七氟醚+Nrf2抑制剂组(S-H+ML385组)。检测大鼠血清炎症因子及氧化应激水平;观察大鼠肺组织病变并计算结核菌数量;检测蛋白表达。结果:与Control组比较,Model组肺组织出现损伤较重,出现大量结核结节和炎症细胞浸润,肺泡结构紊乱,结核菌菌落数升高,IL-6、TNF-α、IL-1β、MDA、ROS水平上升,SOD水平下降,Nrf2、HO-1表达下调(P<0.05);与Model组比较,S-L、S-M、S-H组肺组织损伤均有改善,结核菌菌落数减少,IL-6、TNF-α、IL-1β、MDA、ROS水平降低,SOD水平升高,Nrf2、HO-1表达上调(P<0.05);与S-H组相比,S-H+ML385组肺组织损伤加重,结核菌菌落数增加,IL-6、TNF-α、IL-1β、MDA、ROS水平升高,SOD水平下降,Nrf2、HO-1表达下调(P<0.05)。结论:七氟醚能够改善肺结核大鼠肺组织损伤,可能是通过激活Nrf2/HO-1信号通路实现的。

Objective:To investigate the effect of sevoflurane(Sevo)on lung tissue damage in pulmonary tuberculosis(PTB)rats by regulating the nuclear factor E2 related factor(Nrf2)/heme oxygenase(HO-1)signaling pathway.Methods:A PTB rat model was established.The rats were separated into control group,model group,high-dose,medium-dose,and low-dose sevoflurane groups(S-H group,S-M group,S-L group),and high-dose sevoflurane+Nrf2 inhibitor group(S-H+ML385 group).The levels of inflammatory factors and oxidative stress in serum were detected,the pathological changes in rat lung tissue were observed and the number of tuberculosis bacteria was calculated,and protein expression was detected.Results:Compared with the control group,the model group showed more severe lung tissue damage,with a large number of tuberculosis nodules and inflammatory cell infiltration,and disordered alveolar structure,the number of tuberculosis bacterial colonies increased,and the levels of IL-6,TNF-α,IL-1β,MDA and ROS increased,the level of SOD decreased,and the expression of Nrf2 and HO-1 was down regulated(P<0.05).Compared with the model group,the lung tissue damage was improved in the S-L,S-M,and S-H groups,the number of tuberculosis bacterial colonies decreased,the levels of IL-6,TNF-α,IL-1β,MDA,and ROS decreased,the level of SOD increased,and the expression of Nrf2 and HO-1 was upregulated(P<0.05).Compared with the S-H group,the lung tissue damage in the S-H+ML385 group worsened,the number of tuberculosis bacterial colonies increased,and the levels of IL-6,TNF-α,IL-1β,MDA,and ROS increased,the level of SOD decreased,and the expression of Nrf2 and HO-1 was down regulated(P<0.05).Conclusion:Sevoflurane can improve lung tissue damage in rats with pulmonary tuberculosis,possibly by activating the Nrf2/HO-1 signaling pathway.