Reversal Effect Of Warburg Effect Blocker 2-deoxidation-D-glucose On The Improvement Of Postoperative Cognitive Dysfunction In Patients With Hydrogen Sulfide

[Background and Objective]Although our previous work comfirmed that hydrogen sulfide?H₂S?can improve cognitive dysfunction in elderly postoperative rats,the underlying mechanism is still unclear.Synaptic plasticity is an important foundation for learning and memory formation.The Warburg effect,namely aerobic glycolysis,plays an important role in regulating synaptic plasticity.Furthermore,our previous study found that H₂S could improve the Warburg effect in the hippocampus of elderly postoperative rats,and those protective effects of H₂S on hippocampus could be abolished by Warburg effect inhibitor2-deoxygen-D-glucose?2-DG?.Therefore,we are aimed at investigating whether the improving effect of hydrogen sulfide on postoperative cognitive dysfunction can be reversed by 2-deoxygen-D-glucose.[Methods]Male Sprague-Dawley?SD?rats?18 to 20 months of age?,were pre-treated with NaHS?100?mol/kg/d,i.p.?for two weeks,then exposed to2-DG?100?mol/kg/d,i.p.?for one week.After subjected to laparotomy surgery,they were used to build the model of postoperative cognitive dysfunction.All rats were received the behavioral experiment after subjected to laparotomy surgery 3 days later.The Y-maze test was used to measure the alternation performance of postoperative elderly rats.The Novel Object Recognizition test was used to measure the total time spent with both of the objects and discrimination index.The shuttle test was used to assess active escape times of rats.The Morris Water Maze test was widely used to measure the cross platform times and time in the target quadrant.The open-field test was used to measure the effect of hydrogen sulfide and 2-deoxy-D-glucose on the motor ability of animals[Results]1.In the Y-maze test,NaHS?100?mol/kg/d,i.p.?treatment improved the alternation performance of postoperative elderly rats,but 2-DG can reverse the improving effect of hydrogen sulfide on the alternation performance,suggesting that 2-DG can reverse the improving effect of hydrogen sulfide on postoperatively old rat's spatial recognization ability.2.In the NORT test,NaHS?100?mol/kg/d,i.p.?treatment improved the new object recognition index of POCD rats,which indicated that hydrogen sulfide could improve the cognitive function of POCD rats.However,both in the NaHS,surgery and 2-DG co-treated groups,the new object recognition index of POCD rats in NORT test was reduced,demonstrating that 2-DG can reverse the amendatory effect of hydrogen sulfide on postoperatively old rat's spatial learning and memory ability.3.In the shuttle test,we found that the number of active escapes increased and the active avoidance time reduced in the NaHS and surgery co-treated group,indicating that hydrogen sulfide could improve the cognitive function of POCD rats.However,the improving effect of NaHS?100?mol/kg/d,i.p.?was canceled by 2-DG?100?mol/kg/d,i.p.?treatment.Those results revealed that 2-DG can reverse the amendatory effect of hydrogen sulfide on postoperatively old rat's learning and memory ability.4.In the MWM test,NaHS and surgery co-treated group rats exhibited a decrease in escape latency and an increase in the across times in the platform quadrant.These results indicated that hydrogen sulfide could improve the cognitive function of POCD rats.But the improving effect was canceled after treated with 2-DG for 1 week.These results indicated that 2-DG can reverse the amendatory effect of hydrogen sulfide on postoperatively old rat's spatial learning and memory ability.5.In the open-field test,the spontaneous activity of rats in control group was not significantly different from the control group,suggesting that hydrogen sulfide and 2-deoxy-D-glucose did not affect the motor ability of animals.[Conclusion]2-DG can reverse the improving effect of Hydrogen sulfide on postoperative cognitive disfunction.