Abstract: Objective: To investigate the protective effect of carnosine on the vascular cognitive impairment(VCI) of the rats, and to elucidate its mechanism. Methods: Fifty SD rats were randomly divided into sham operation group, model group (bilateral common carotid artery occlusion for 10 min→reperfusion for 10 min→occlusion for 10 min) and different doses of carnosine group (bilateral common carotid artery occlusion for 10 min→reperfusion for 10 min→occlusion for 10 minutes + 100, 300,and 900 mg·kg^-1·d^-1 carnosine);there were 10 rats in each group. The carnosine was administered by gavage once a day from 21 d before modeling to 12 d after modeling. Morris water maze test was carried out on the 7th day after operation to measure the learning and memory ability of the rats. The hippocampus tissue of the rats was obtained on the 12th day; the levels of carnosine and reduced glutathione(GSH) in hippocampus tissue of the rats in various groups were detected by high performance liquid chromatography (HPLC),the expression of glial fibrillary acidic protein(GFAP) in CA1 area of hippocampus of the rats in various groups was detected by immunohistochemistry method.The expression levels of phosphate nuclear factor-kappa B p65(p-NF-κB p65) protein in hippocampus tissue of the rats in various groups were determined by Western blotting method. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in hippocampus tissue of the rats in various groups were detected by ELISA method. Results: Compared with sham operation group, the pyramidal cells in the CA1 area of hippocampus of the rats in model group were partially absent, the escape latency was significantly prolonged (P<0.01), and the time staying in the platform quadrant was significantly shortened (P<0.01);the levels of carnosine and GSH in hippocampus tissue were decreased (P<0.01), the number of GFAP positive cells was increased, the expression level of p-NF-κB p65 protein was increased (P<0.01),and the levels of IL-1β and TNF-α were increased (P<0.01).Compared with model group, the pyramidal cells in CA1 area of hippocampus of the rats in different doses of carnosine groups were arranged in order, the escape latency was significantly shortened (P<0.01), and the time staying in the platform quadrant was significantly increased (P<0.01);the levels of carnosine and GSH in hippocampus tissue of the rats were increased (P<0.05 or P<0.01), the number of GFAP positive cells was decreased, the expression levels of p-NF-κB p65 protein were decreased(P<0.01),and the levels of IL-1β and TNF-α were decreased (P<0.01). Conclusion: Carnosine has the protective effect in the rats with VCI,and its mechanism may be related to the improvement of antioxidant capacity,inhibition of NF-κB pathway activation, thus inhibiting the abnormal activation of astrocytes and reducing inflammation.

Key words: carnosine, vascular cognitive impairment, nuclear factor kappa B, glutathione, astrocyte