关键词: 肌肽, 　认知障碍, 　NF-&kappa, B, 　TNF-&alpha, 、IL-1&beta, 　SOD, 　MDA

Abstract:

Objective     To investigate the effect of Carnosine (CAR) on cognitive function and oxidative stress and NF-κB signaling pathway in diabetic rats.   Methods    Fifty male SD rats, except the normal group (n=8), were given high fat and sugar diet, and intraperitioneal injection of STZ to establish type Ⅱ diabetes rats. The rats were randomly divided into the diabetic model group and Carnosine groups with different doses (100, 300 and 900 mg/kg). All drugs were administrated for 56 days.  The behavior tests were performed on the Morris water maze method. HE stain were used to observe the pathological changes of the hippocampus. The activity of SOD and the content of MDA in the hippocampus were detected by  respective commercial kits. The content of GSH and carnosine in hippocampus tissue were detected by HPLC. Western Blot were used to detect the expression of TNF-α, IL-1β in cytoplasm and NF-κB p65 in nucleus.   Results    Compared with diabetic group, Carnosine groups improved significantly learning and memory ability and the morphology of hippocampal neuronal cell in diabetic rats, enhanced the activity of SOD, the content of GSH and carnosine in the hippocampus of diabetic rats, inhibited the content of MDA, which, at the same time, reduced significantly the nuclear transfer of NF-κB with the nucleus of hippocampus in diabetic rats and down-regulated the expression of downstream inflammatory cytokines TNF-α and IL-1β.   Conclusion    Carnosine may prevent cognitive dysfunction in DM rats. The mechanism may be in connection with its function that it can inhibit oxidative stress, reduce NF-κB translocating into the nucleus and the expression of TNF-α and IL-1β.

Key words: Carnosine, 　Cognitive impairment;   , NF-κB;    , TNF-α, , IL-1β;   , SOD;    , MDA