The Effect Of Green Tea Polyphenols Pretreatment On Cognitive Function In Mice After Long-time Isoflurane Anesthesia

Objective: The present study is designed to investigate the effects of green tea polyphenols(GTP)on cognitive function after isoflurane anesthesia in mice,and to explore the potential underlying mechanisms from aspect of oxidative stress.Methods: 8-week-old male C57BL/6J mice were randomly divided into one of following six groups: control group(Con),anesthesia group(Anes),GTP-multiple dose group(GTP-MD),GTP-MD+anesthesia group(GTP-MD+Anes),GTP-single dose group(GTP-SD),GTP-SD+anesthesia group(GTP-SD+Anes).Mice in Anes group,GTP-MD+Anes group and GTP-SD+Anes group were exposed to 1.4%isoflurane for 6h in a temperature-controlled chamber.GTP-MD and GTP-MD+Anes groups of mice were administered intraperitoneally with GTP at 25mg/kg for 7consecutive days until gas inhalation.GTP-SD and GTP-SD+Anes groups of mice were treated in accordance with above manner at 75 mg/kg on the 7th day.Fear conditioning test and novel object recognition were conducted on Days 1,3 and 7after general anesthesia to evaluate the effects of isoflurane inhalation on cognitive function in mice.Superoxide dismutase(SOD)activity levels were estimated using the Total Superoxide Dismutase Assay Kit with WST-8 on Day 3 after general anesthesia.Western blot was preformed to measure the protein levels of phosphor-calcium/calmodulin dependent protein kinase II(p-CAMKII),phosphor-c AMP-response element binding protein(p-CREB)and brain derived neurotrophic factor(BNDF)on Day 3 after general anesthesia.Results: Fear conditioning test and novel object recognition showed that the 6-h’isoflurane exposure could cause damage to the postanesthesia cognition on Day 3. Multiple dose of GTP at 25 mg/kg intraperitoneally injected for 7 consecutive days mitigated the isoflurane-induced cognitive dysfunction.However,single dose of GTP at 75 mg/kg failed to reverse the cognition function impairment following 6h isoflurane anesthesia.In addition,the SOD level in the hippocampus of mice on Day3 after long-term isoflurane anesthesia showed a significant decline,and the down-regulation of SOD level was effectively alleviated by multi-dose GTP treatment.Western blot results showed that isoflurane anesthesia decreased the hippocampus p-CREB,p-Ca MKII and BDNF protein levels on Day 3.GTP pretreatment with multiple-dose rescued the downregulation of the above protein levels.However,single dose of GTP had no significant effect on SOD,p-CREB,p-Ca MKII and BDNF levels in the hippocampus of mice on Day 3 day after anesthesia.Conclusion: Multiple dose of GTP(25 mg/kg/d)pretreatment can effectively improve the cognitive dysfunction caused by isoflurane anesthesia,which may be related to long-term intake of GTP increasing the level of SOD related to oxidative stress in the hippocampus.