Relationship between SIRT1-ERK1∕2 pathway and chikusetsu saponin IVa-induced reduction of isoflurane-elicited neurotoxicity in fetal rats: an in vitro experiment / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the relationship between silent information regulator 1 ( SIRT1)-extracellular-regulated kinase1∕2 ( ERK1∕2) pathway and chikusetsu saponin IVa-induced reduc-tion of isoflurane-elicited neurotoxicity in fetal rats in an in vitro experiment. Methods The hippocampal neurons isolated from rats at 16-18 days of gestation were primarily cultured for 7 days and divided into 3 groups ( n = 6 each) using a random number table method: control group ( Con group) , isoflurane group (Iso group) and chikusetsu saponin IVa plus isoflurane group (ChIV+Iso group). Hippocampal neurons were cultured routinely for 6 h in Con group. Hippocampal neurons were exposed to 1. 8％ isoflurane for 6 h in an incubator in Iso group. Chikusetsu saponin IVa 25μg∕ml was added to the culture medium, and hipp-ocampal neurons were incubated for 6 h and then exposed to 1. 8％ isoflurane for 6 h in an incubator in ChIV+Iso group. The supernatant was collected for determination of the amount of lactic dehydrogenase ( LDH) released, neuronal viability ( by CCK-8) and expression of SIRT1, ERK1∕2 and phosphorylated ERK1∕2 ( p-ERK1∕2) ( by Western blot) . Results Compared with Con group, the neuronal viability was significantly decreased, the amount of LDH released was increased, and the expression of SIRT1 and p-ERK1∕2 was down-regulated in Iso group ( P<0. 05) . Compared with Iso group, the neuronal viability was significantly increased, the amount of LDH released was decreased, and the expression of SIRT1 and p-ERK1∕2 was up-regulated in ChIV+Iso group ( P<0. 05) . Conclusion The mechanism by which chikuset-su saponin IVa reduces isoflurane-elicited neurotoxicity is related to activating SIRT1-ERK1∕2 pathway in fe-tal rats in an in vitro experiment.