关键词: 异氟醚, 内质网应激, 缺氧/复氧模型, 细胞凋亡。

Abstract: Objective to investigate the effects of isoflurane treatment on hypoxia/reoxygenation-induced endoplasmic reticulum stress (ERS) and apoptosis in HK-2. Methods After treatment of hypoxia/reoxygenation in HK-2, 2.56% isoflurane was added and incubated for 1, 4 and 8h. Then the lactate dehydrogenase (LDH) and MTT were measured for detecting the hypoxia/reoxygenation-induced injury and cell viability in HK-2 cells. Flow cytometry was performedto detect apoptosis. RT-qPCR and semi-quantitative Western blot were employed for analyzing hallmarks of endoplasmic reticulum stress, GRP78, CHOP and caspase-12. Results After 4 and 8-hour co-incubation with 2.56% isoflurane, LDH is lower and MTT is higher in treated groups, compared with mock group (P＜0.05), indicating the promoting effect of isoflurane treatment on cell survival. 1-hour co-incubation with 2.56% isoflurane presented undetectable effect on cell survival. Consistently, Annexin V/PI double staining results present that, the apoptotic rate in 4h-treated and 8h-treated group is （12.1±1.3%）和（7.1±1.1）%, which are significantly lower than mock group (（24.2±4.6）% and（13.3±3.1）%, P＜0.05). GRP78 and caspase-12, but not CHOP were upregulated in treated cells compared to untreated cells. After isoflurane treatment, caspase-12 activity was downregulated. Conclusion Isoflurane treatment inhibited ER stress-induced apoptosis in hypoxia/reoxygenation model cells by downregulating caspase-12 activity.

Key words: Isoflurane, Endoplasmic reticulum stress (ER stress), hypoxia/reoxygenation, apoptosis.