Effects Of Carnosine On Oxidative Stress And NF-κB Signaling Pathway In Rats With Vascular Cognitive Impairment

Objective To explore the protective effect and mechanism of carnosine gavage on vascular cognitive impairment in rats.Methods50 male SD rats were randomly divided into 5 groups: Sham operation group,VCI group,VCI + Carnosine(100 mg · kg-1 · d-1),VCI + Carnosine(300mg · kg-1· d-1),VCI + Carnosine(900 mg · kg-1·d-1)group.The VCI model was made by intraperitoneal injection of sodium nitroprusside and occlusion of bilateral common carotid arteries of 10 min-reperfusion for 10 min-occlusion for10 min.Administration of 100,300,or 900 mg · kg-1carnosine by gavage from21 days before modeling to 12 days after modeling.Morris water maze test was started on the 7th day after surgery to determine the learning and memory ability of rats;the contents of reduced glutathione in the hippocampus of rats were determined by HPLC on the 12 days after operation.Immunohistochemical method was used to observe the expression of glial fibrillary acidic protein in CA1 region of hippocampus.Western blot was used to detect the content of phosphorylated NF-κB p65 protein in rat hippocampus.ELISA method was used to detect the expression of IL-1β and TNF-α in rat hippocampus.Results Compared with the sham operation group,the pyramidal cells in CA1 area of hippocampus of rats in the VCI group were partially absent,the escape latency was also significantly prolonged(P<0.01),and the time staying in target quadrant was significantly shortened(P<0.01);The content of carnosine and GSH in the hippocampus of rats decreased significantly(P <0.01),the number of GFAP positive cells increased,the expression of p-NF-κB p65 protein increased(P <0.01),the expression of IL-1β and TNF-α increased(P <0.01).Compared with the VCI group,the vertebral cells in CA1 area of hippocampus of rats in different doses of carnosine group were arranged orderly,the escape latency was also shortened(P <0.01),and the time staying in target quadrant was prolonged(P <0.01);The content of carnosine and GSH in the hippocampus of rats increased significantly(P <0.05 or P <0.01),the number of GFAP positive cells decreased,the expression of p-NF-κB p65 protein decreased(P <0.01),the expression of IL-1β and TNF-α decreased(P<0.01).Conclusions Carnosine had a protective effect on VCI in rats,which may be related to the increase of antioxidant capacity,inhibition of activation of NF-κB pathway,inhibition of abnormal activation of astrocytes and reduction of inflammation.