Association of the lncRNA-GAS5 promoter region rs145204276 polymorphism with sevoflurane maintenance anesthesia outcomes on patients undergoing laparoscopic cholecystectomy.

Abstract

To further investigate how sevoflurane affects the oxidative stress injury (OSI) in patients undergoing laparoscopic cholecystectomy (LC). A prospective cohort study was carried out at Shandong Provincial Third Hospital, Jinan, China on 82 gallstone patients who underwent LC, with sevoflurane maintenance during surgery. Genotyping analysis of the rs145204276 polymorphism was performed using the TaqMan platform. Oxidative stress injury and liver injury parameters were also examined. Lipopolysaccharide (LPS)-induced macrophages, which were challenged with sevoflurane, propofol, or the lncRNA-GAS5 overexpressing plasmid, were used to evaluate the effect of Sevoflurane on lncRNA-GAS5-mediated macrophage polarization. At TM1 and TM2, the levels of OSI markers and long noncoding (lnc) RNA-GAS5 were not obviously different, whereas at the TM3 time point, these indices were significantly different between the Del-Sevoflurane and Del-Propofol subgroups. These indices were not different between the Ins-sevoflurane and Ins-Propofol subgroups at any time point. Cell-based experiments demonstrated that Sevoflurane could increased the lncRNA-GAS5 level in LPS-induced Del-macrophages (p=0.0058), but Propofol did not have this effect (p=0.847). Both Sevoflurane and Propofol did not have the effect on lncRNA-GAS5 level in LPS-induced Ins-macrophages (p=0.321 and p=0.822, respectively). Sevoflurane maintenance can decrease OSI during LC in the Del genotype of the rs145204276 polymorphism. The Del genotype facilitates lncRNA-GAS5 up-regulation under Sevoflurane exposure and therefore decrease the extent of M1 macrophage polarization.