Carnosine Prevents Cognitive Impairment In Type 2 Diabetic Rats And Its Mechanism

ObjectiveTo observe the effects of carnosine on cognitive impairment,hippocampal neurons,hippocampal oxidative stress and NF-?B signaling paythway in type 2diabetic rats.Methods50 male Sprague-Dawley rats were randomly selected and fed with 8normal diets as control group?Con?.The other 42 rats were fed with high-sugar and high-fat and intraperitoneal injection of streptozotocin?STZ?30mg·kg^-1.Establish a T2DM model.After successful modeling,the rats were randomly divided into type 2 diabetes groups and carnosine?CAR?(100,300,900mg·kg^-1)groups.Rats in the low,medium and high doses of carnosine were intragastrically administered with CAR 100,300,900mg·kg^-1·d^-1 respectively;the Con group and T2DM group were given the same volume of distilled water.Rats are still CAR during the water maze experiment.The blood glucose and body weight of rats were measured regularly.Morris water maze test was performed after CAR 51d.The pathological changes of neurons in the hippocampus CA1 area were observed by HE staining.Immunohistochemical detection of NF-?B p65 protein expression.The malondialdehyde?MDA?content and superoxide dismutase?SOD?activity in a hippocampus were detected by the kit method.The contents of glutathione?GSH?and carnosine in hippocampus were detected by high performance liquid chromatography?HPLC?.Expressions of cytoplasmic TNF-?,IL-1?and nuclear NF-?B p65 in hippocampus were detected by Western blotting.ResultsCompared with the Con group,the T2DM model group?1?increased of rats the blood glucose and decreased of rats the body weight.?2?Cognitive impairment appeared in rats in the water maze experiment,which showed that the escape latency was significantly prolonged?P<0.01?and the number of rats crossing the platform was significantly decreased?P<0.01?.?3?Rat hippocampal neurons are sparsely disordered with irregular cell morphology or spindle shape and nuclear condensation.?4?Increased NF-?B p65 positive cells in the hippocampus of rats?P<0.01?.?5?The activity of SOD in the hippocampus of rats decreased and the content of MDA increased.?6?The levels of GSH and carnosine in the hippocampus of rats were significantly reduced.?7?The expression level of NF-?B p65 protein in rat hippocampus was significantly increased and the expression levels of cytoplasmic TNF-?and IL-1?protein were increased.Compared with the T2DM model group,?1?CAR group can increase weight slightly and the blood glucose did not change significantly.?2?The CAR group shortened the escape latency of rats?P<0.01?and increased the number of crossing platforms?P<0.01?.?3?The pyramidal cells in the hippocampal CA1region of the CAR group were arranged neatly,The morphology was complete and the neurons were improved.?4?The NF-?B p65 positive cells in the hippocampus of the CAR group were significantly decreased?P<0.01 or P<0.05??5?The activity of SOD in the hippocampus of rats increased and the content of MDA decreased.?6?The content of GSH and carnosine in hippocampus of rats increased significantly.?7?CAR groups significantly inhibited the transfer of NF-?B p65 protein into the nucleus of rat hippocampus and down-regulated TNF-?and IL-1?protein of expression.ConclusionsType 2 diabetes mellitus can cause abnormal morphology of pyramidal cells in the hippocampal CA1 region of rats and the hippocampus is in an imbalance of oxidative stress.The local inflammatory factors TNF-?and IL-1?are overexpressed,leading to cognitive impairment,while carnosine can be improved.Cognitive impairment of T2DM rats may be related to the inhibition of oxidative stress in the hippocampus,reduce NF-?B p65 translocation into the nucleus and the expression of TNF-?and IL-1?.