Abstract：Objective To investigate the protective effect and mechanism of sevoflurane preconditioning on lung injury induced by the distal ischemia reperfusion (IR) of rat limbs. Methods Twenty-eight healthy adult male SD rats were selected. The rats were randomly divided into 4 groups (7 rats per group) by using a random number table. In the sham operation group (sham group), only the bilateral femoral arteries and veins were isolated without clamping, and the materials were taken after 5 h of exposure. The sevoflurane preconditioning+sham operation group (S-S group) inhaled 2.5% sevoflurane for 30 min. Then, the operation was the same as that of the sham group. In the distal limb IR group (IR group), the rat model of the lower limb IR was established by isolating the bilateral femoral veins and the femoral arteries, clamping the bilateral femoral arteries for 3 h, restoring blood supply for 2 h after reperfusion, and then extracting the materials. The sevoflurane preconditioning+distal limb IR group (S-IR group) was pretreated with sevoflurane in advance by the same method as that of the S-S group. The operation after sevoflurane pretreatment was the same as that of the IR group. At the end of the experiment, the left ventricular blood and bilateral lung tissues in each group were collected. (1) The wet weight/dry weight (W/D) ratio and total lung water content (TLW) were measured. (2) Pathological changes of the lung tissues were observed under a light microscope. (3) The content of oxidative stress factors, including lipid oxidation (MDA) and superoxide dismutase (SOD), and the levels of inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, in the lung tissues and sera were measured by corresponding kits. (4) Protein expression levels of phosphorylated p38α mitogen-activated protein kinase (p-p38), phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), and silent information regulator factor-1 (SIRT1) in the lung tissues were determined by Western blot. Results (1) The W/D and TLW of the IR and S-IR groups were higher than those of the sham and S-S groups, and corresponding values of the S-IR group were lower than those of the IR group; all with statistically significant differences (F=144.75, 133.21; all P values<0.001). (2) Histopathological sections of the lung tissues in the sham group showed normal alveolar morphological structure, no inflammatory cell infiltration in the alveoli, and no fluid accumulation in the alveolar septa. Histopathological sections of the lungs in the S-S group showed grossly normal alveolar architecture, no obvious thickening of the alveolar walls, and no inflammatory cell infiltration in the alveolar septa. These results suggested no significant damage. Compared with the sham group, the histopathological sections of lungs in the IR group showed severe destruction of the alveolar morphological structure, extensive alveolar septal thickening, alveolar interstitium filled with a large amount of edema fluid, and infiltration with a large number of inflammatory cells. Inflammatory cell infiltration and edema were remarkably reduced in the S-IR group compared with the IR group. (3) The levels of IL-1β, IL-6, TNF-α, and MDA in the lung tissues and sera of the IR and S-IR groups were higher than those of the sham and S-S groups, while those of the S-IR group were lower than those of the IR group; all with statistically significant differences (all P values <0.05). The SOD contents in the IR and S-IR groups were lower than those in the sham and S-S groups, and that in the S-IR group was higher than that in the IR group; all with statistically significant differences (all P values <0.05). No significant differences were found in the amounts of IL-1β, IL-6, TNF-α, MDA, and SOD in the lung tissues between the S-S and sham groups (all P values >0.05). The p-p38 protein levels in the IR and S-IR groups were higher than those in the sham and the S-S groups, and that in the S-IR group was lower than that in the IR group; all with statistically significant differences (all P values <0.05). (4) The relative protein expression levels of p-AMPK and SIRT1 in the lung tissues in the IR and S-IR groups were lower than those in the sham and S-S groups, and that in the S-IR group was higher than that in the IR group; all with statistically significant differences (all P values <0.05). No significant differences were found in the relative protein expression levels of p-p38, p-AMPK, and SIRT1 between the lung tissues of the S-S and sham groups (all P values >0.05). Conclusion For the lung injury induced by distal limb IR, sevoflurane preconditioning may play a protective role. The mechanism may be related to the promotion of p-AMPK, SIRT1 protein expression, and inhibition of p-p38 protein expression, which may then attenuate lung inflammation.
杨栋栋, 凌云志, 孙宜云, 李芷依, 王倩, 高兴悦, 谢亚琼. 七氟烷预处理对大鼠肢体远端缺血再灌注诱导肺损伤的保护作用[J]. 中华解剖与临床杂志, 2022, 27(6): 411-417.
Yang Dongdong, Ling Yunzhi, Sun Yiyun, Li Zhiyi, Wang Qian, Gao Xingyue, Xie Yaqiong. Protective effect of sevoflurane preconditioning on lung injury induced by distal limb ischemia-reperfusion. Chinese Journal of Anatomy and Clinics, 2022, 27(6): 411-417.
Orhan M, Taş Tuna A, Ünal Y, et al.The effects of amantadine on lung tissue in lower limb ischemia/reperfusion injury model in rats[J]. Turk Gogus Kalp Damar Cerrahisi Derg, 2021, 29(1): 77-83. DOI: 10.5606/tgkdc.dergisi.2021.19884.
[2]
Xue BB, Chen BH, Tang YN, et al.Dexmedetomidine protects against lung injury induced by limb ischemia-reperfusion via the TLR4/MyD88/NF-κB pathway[J]. Kaohsiung J Med Sci, 2019, 35(11): 672-678. DOI: 10.1002/kjm2.12115.
[3]
Lou Y, Yu Q, Xu K, et al.Electroacupuncture pre‑conditioning protects from lung injury induced by limb ischemia/reperfusion through TLR4 and NF‑κB in rats[J]. Mol Med Rep, 2020, 22(4): 3225-3232. DOI: 10.3892/mmr.2020.11429.
[4]
Cearra I, Herrero de la Parte B, Ruiz Montesinos I, et al. Effects of folinic acid administration on lower limb ischemia/reperfusion injury in rats[J]. Antioxidants (Basel), 2021, 10(12). DOI: 10.3390/antiox10121887.
[5]
Huang X, Ying J, Yang D, et al.The mechanisms of sevoflurane-induced neuroinflammation[J]. Front Aging Neurosci, 2021, 13: 717745. DOI: 10.3389/fnagi.2021.717745.
[6]
Xu G, Wang X, Xiong Y, et al.Effect of sevoflurane pretreatment in relieving liver ischemia/reperfusion-induced pulmonary and hepatic injury[J]. Acta Cir Bras, 2019, 34(8): e201900805. DOI: 10.1590/s0102-865020190080000005.
[7]
Li Y, Xing N, Yuan J, et al.Sevoflurane attenuates cardiomyocyte apoptosis by mediating the miR-219a/AIM2/TLR4/MyD88 axis in myocardial ischemia/reperfusion injury in mice[J]. Cell Cycle, 2020, 19(13): 1665-1676. DOI: 10.1080/15384101.2020.1765512.
[8]
Zou R, Wang MH, Chen Y, et al.Hydrogen-rich saline attenuates acute lung injury induced by limb ischemia/reperfusion via down-regulating chemerin and NLRP3 in rats[J]. Shock, 2019, 52(1): 134-141. DOI: 10.1097/SHK.0000000000001194.
[9]
Xue BB, Chen BH, Tang YN, et al.Dexmedetomidine protects against lung injury induced by limb ischemia-reperfusion via the TLR4/MyD88/NF-κB pathway[J]. Kaohsiung J Med Sci, 2019, 35(11): 672-678. DOI: 10.1002/kjm2.12115.
[10]
Zhao YR, Lv WR, Zhou JL.Role of carbonyl sulfide in acute lung injury following limb ischemia/reperfusion in rats[J]. Eur J Med Res, 2017, 22(1): 12. DOI: 10.1186/s40001-017-0255-z.
[11]
Ozdemirkan A, Kucuk A, Gunes I, et al.The effect of cerium oxide on lung injury following lower extremity ischemia-reperfusion injury in rats under desflurane anesthesia[J]. Saudi Med J, 2021, 42(11): 1247-1251. DOI: 10.15537/smj.2021.42.11.20210104.
[12]
Huang D, Zhang LL, Zhou B, et al.Rapamycin inhibits LOC102553434-mediated pyroptosis to improve lung injury induced by limb ischemia-reperfusion[J]. 3 Biotech, 2021, 11(7): 335. DOI: 10.1007/s13205-021-02708-9.
[13]
Lin W, Jia D, Fu C, et al.Electro-acupuncture on ST36 and SP6 acupoints ameliorates lung injury via sciatic nerve in a rat model of limb ischemia-reperfusion[J]. J Inflamm Res, 2020, 13: 465-470. DOI: 10.2147/JIR.S264093.
[14]
Bertani A, Miceli V, De Monte L, et al.Donor preconditioning with inhaled sevoflurane mitigates the effects of ischemia-reperfusion injury in a swine model of lung transplantation[J]. Biomed Res Int, 2021, 2021: 6625955. DOI: 10.1155/2021/6625955.
[15]
Liu X, Wang L, Xing Q, et al.Sevoflurane inhibits ferroptosis: a new mechanism to explain its protective role against lipopolysaccharide-induced acute lung injury[J]. Life Sci, 2021, 275: 119391. DOI: 10.1016/j.lfs.2021.119391.
[16]
Fan L, Chen D, Wang J, et al.Sevoflurane ameliorates myocardial cell injury by inducing autophagy via the deacetylation of LC3 by SIRT1[J]. Anal Cell Pathol (Amst), 2017, 2017: 6281285. DOI: 10.1155/2017/6281285.
[17]
Tuncay A, Sivgin V, Ozdemirkan A, et al.The effect of cerium oxide on lung tissue in lower extremity ischemia reperfusion injury in sevoflurane administered rats[J]. Int J Nanomedicine, 2020, 15: 7481-7489. DOI: 10.2147/IJN.S263001.
[18]
Takhtfooladi HA, Takhtfooladi MA.Effect of curcumin on lung injury induced by skeletal muscle ischemia/reperfusion in rats[J]. Ulus Travma Acil Cerrahi Derg, 2019, 25(1): 7-11. DOI: 10.5505/tjtes.2018.83616.
[19]
Chu SJ, Tang SE, Pao HP, et al.Protease-activated receptor-1 antagonist protects against lung ischemia/reperfusion injury[J]. Front Pharmacol, 2021, 12: 752507. DOI: 10.3389/fphar.2021.752507.
[20]
Wang Y, Zhang X, Tian J, et al.Sevoflurane alleviates LPS‑induced acute lung injury via the microRNA‑27a‑3p/TLR4/MyD88/NF‑κB signaling pathway[J]. Int J Mol Med, 2019, 44(2): 479-490. DOI: 10.3892/ijmm.2019.4217.
[21]
Porteous MK, Diamond JM, Christie JD.Primary graft dysfunction: lessons learned about the first 72 h after lung transplantation[J]. Curr Opin Organ Transplant, 2015, 20(5): 506-514. DOI: 10.1097/MOT.0000000000000232.
[22]
Xiao YT, Yan WH, Cao Y, et al.P38 MAPK pharmacological inhibitor SB203580 alleviates total parenteral nutrition-induced loss of intestinal barrier function but promotes hepatocyte lipoapoptosis[J]. Cell Physiol Biochem, 2017, 41(2): 623-634. DOI: 10.1159/000457933.
[23]
Mo L, Hong S, Li Y, et al.Sevoflurane inhibited inflammatory response induced by TNF-α in human trophoblastic cells through p38MAPK signaling pathway[J]. J Recept Signal Transduct Res, 2020, 40(3): 218-223. DOI: 10.1080/10799893.2020.1726951.
[24]
Wang L, Ma H, Xue Y, et al.Berberine inhibits the ischemia-reperfusion injury induced inflammatory response and apoptosis of myocardial cells through the phosphoinositide 3-kinase/RAC-α serine/threonine-protein kinase and nuclear factor-κB signaling pathways[J]. Exp Ther Med, 2018, 15(2): 1225-1232. DOI: 10.3892/etm.2017.5575.
[25]
Yu X, Zhang F, Shi J.Effect of sevoflurane treatment on microglia activation, NF-kB and MAPK activities[J]. Immunobiology, 2019, 224(5): 638-644. DOI: 10.1016/j.imbio.2019.07.004.
[26]
Zhang H, Yan Q, Wang X, et al.The role of mitochondria in liver ischemia-reperfusion injury: from aspects of mitochondrial oxidative stress, mitochondrial fission, mitochondrial membrane permeable transport pore formation, mitophagy, and mitochondria-related protective measures[J]. Oxid Med Cell Longev, 2021, 2021: 6670579. DOI: 10.1155/2021/6670579.
[27]
Pau MC, Zinellu E, Fois SS, et al.Circulating malondialdehyde concentrations in obstructive sleep apnea (OSA): a systematic review and meta-analysis with meta-regression[J]. Antioxidants (Basel), 2021, 10(7):1053. DOI: 10.3390/antiox10071053.
[28]
Chazelas P, Steichen C, Favreau F, et al.Oxidative stress evaluation in ischemia reperfusion models: characteristics, limits and perspectives[J]. Int J Mol Sci, 2021, 22(5): 2366. DOI: 10.3390/ijms22052366.
[29]
Zheng P, Kang J, Xing E, et al.Lung inflation with hydrogen during the cold ischemia phase alleviates lung ischemia-reperfusion injury by inhibiting pyroptosis in rats[J]. Front Physiol, 2021, 12: 699344. DOI: 10.3389/fphys.2021.699344.
[30]
Ding R, Wu W, Sun Z, et al.AMP-activated protein kinase: an attractive therapeutic target for ischemia-reperfusion injury[J]. Eur J Pharmacol, 2020, 888: 173484. DOI: 10.1016/j.ejphar.2020.173484.
[31]
Huang XT, Liu W, Zhou Y, et al.Galectin-1 ameliorates lipopolysaccharide-induced acute lung injury via AMPK-Nrf2 pathway in mice[J]. Free Radic Biol Med, 2020, 146: 222-233. DOI: 10.1016/j.freeradbiomed.2019.11.011.
[32]
Lu Q, Lin X, Wu J, et al.Matrine attenuates cardiomyocyte ischemia-reperfusion injury through activating AMPK/Sirt3 signaling pathway[J]. J Recept Signal Transduct Res, 2021, 41(5): 488-493. DOI: 10.1080/10799893.2020.1828914.
[33]
Xu C, Wang J, Fan Z, et al.Cardioprotective effects of melatonin against myocardial ischaemia/reperfusion injury: activation of AMPK/Nrf2 pathway[J]. J Cell Mol Med, 2021, 25(13): 6455-6459. DOI: 10.1111/jcmm.16691.
[34]
Ogura Y, Kitada M, Koya D.Sirtuins and renal oxidative stress[J]. Antioxidants (Basel), 2021, 10(8):1198. DOI: 10.3390/antiox10081198.
[35]
Wang R, Xie Y, Qiu J, et al.The effects of dexmedetomidine in a rat model of sepsis-induced lung injury are mediated through the adenosine monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) pathway[J]. Med Sci Monit, 2020, 26: e919213. DOI: 10.12659/MSM.919213.
2022, Vol. 27 
