The Protective Effects And Mechanisms Of High-dose Vitamin C On Sepsis Associated Cognitive Impairment In Rats

Objective: To observe the effect of early administration of high-dose vitamin C on cognitive function of septic rats and to explore its possible brain protective mechanism.Methods: The healthy and clean adult male SD rats were divided into three groups: control group(sham group),sepsis group(clp group)and vitamin C intervention group(clp +vitc group).Rats were suffered to sepsis by cecal ligation and punctuer(clp).The rats of vitamin C intervention group was given high-dose vitamin C(200 mg/kg)at 30 min and 12 h after operation.The Neurobehavioral scores of rats in three groups were evaluated at 24 hours after operation.Rats were sacrificed and brain tissues were obtained at 24 h after operation.The concentration of TNF-?,Il-6,Il-10 and MMP-9 in the plasma and hippocampal tissues of rats in each group was detected by ELISA method.The levels of SOD and MDA in plasma and hippocampal tissue of rats were detected by colorimetric method.The histopathologic changes of hippocampus tissue were observed by Nissl staining.The protein expression of total Nrf2,nuclear Nrf2 and HO-1 was detected by Western Blotting.The survival rate was recorded within 7days.At 10 days after operation,behavior test was performed to evaluate cognitive impairment.Results: Compared with the control group,the neurobehavioral scores were significantly reduced,the escape latency was significantly prolonged,the retention time of the target quadrant was significantly reduced,and the number of crossing the platform was significantly reduced in the septic group and the vitamin C group(P<0.05).compared with the septic group,the neurobehavioral score was significantly increased,the escape latency was significantly shortened,the retention time of the target quadrant was significantly increased(P<0.05),and the number of crossing the platform was increased in the vitamin C intervention group(P>0.05).Compared with the control group,the hippocampal neurons in the septic group were sparsely arranged,disordered,partially structured,and the number of pyramidal neurons was significantly reduced(P<0.01).Compared with the septic group,the disorder of hippocampal neuron alleviated and more pyramidal neurons was observed in the vitamin C group(P<0.05).Compared with the control group,the levels of TNF-?,IL-6,IL-10 and MDA in serum and hippocampal tissue were significantly increased in septic group and vitamin C group(P<0.05),but the level of SOD was decreased,the levels of MMP9,the protein expression of total Nrf2,nuclear Nrf2 and HO-1 in hippocampal tissue were all increased in the septic group and the vitamin C group(P<0.05).compared with the septic group,the levels of TNF-?,IL-6 and MDA in serum and hippocampal tissue were significantly decreased(P<0.05),the levels of SOD and IL-10 were significantly increased(P<0.05),The level of MMP9 in hippocampal tissue was decreased significantly,the protein expression of total Nrf2,nuclear Nrf2 and HO-1 were increased in the vitamin C intervention group(P<0.05).The 7 day Survival rates of control group,sepsis group and vitamin C group were 100%,47%,58%.and there were no statistical difference between sepsis group and vitamin C group(P>0.05).Conclusions: High-dose vitamin C can improve the spatial learning and memory ability of septic rats,meanwhile,it can obviously ameliorate the pathological damage of hippocampal tissue of septic rats,its protective mechanism may be related to inhibition of inflammatory factors,alleviate oxidative stress and decrease of blood-brain barrier permeability.and may play a brain protective role by activating the Nrf2/HO-1 pathway.