The Role Of Rapamycin On Cognitive Dysfunction Of Diabetic Mice And Apoptosis-associated Proteins

Objective:Study the role of mTOR inhibitor rapamycin in cognitive dysfunction and neuron cell apoptosis in hippocampus of the diabetic mice induced by STZ(Streptozocin, STZ).Methods:Male C57BL/6J mice were divided into two groups randomly as follows:normal control group(Con group,n=10), diabetic group(n=40). After adaptive feeding for one week, DM group mice were injected intraperitoneally with STZ(200mg/kg), and blood glucose was measured after48hours, and the mice whose blood glucose were more than16.7mmol/1were the successful modeling (n=38). the Con group mice were injected with the same amount of citric acid buffer. After eatablish the model successfully, the diabetic group were equally divided into diabetic control group (DM group, n=19) and diabetes with rapamycin intervention group (Rap group, n=19). Rap group were given the rapamycin solution(rapamycin powder was dissolved in DMSO solution with1mg/800μl ratio,a single dose of2000μL/kg) by intraperitoneal injection everyday, but Con group and DM group were given the same amount of DMSO solution by intraperitoneal injection everyday. The Morris water maze test detect the cognitive function of mice after one month of drug intervention. Then blood was collected for measurement of blood glucose before the animals were decapitated. Left and right hippocampus of the mice were preserved by liquid nitrogen in order to extract the tissue protein for taking western bloting of p-mTOR、 p70S6K、Bax and Bcl-2.Results:1.Morris water maze test showed that, compared with the CON group, the escape latency time of the DM group was longer and the time of the DM group spend in original platform quadrant was shorter, the difference was statistically significant (P<0.05); compared with the DM group, the escape latency time of the Rap group was shorter and the time of the Rap group spend in original platform quadrant was longer, the difference was statistically significant (P<0.05).2. Compared with the CON group, The expression of tissue protein p-mTOR (Ser2448) and p70S6K(Thr421/Ser424)were increased in the DM group, the differences were statistically significant (P<0.05); Compared with the DM group, The expression of tissue protein p-mTOR (Ser2448) and p70S6K (Thr421/Ser424) were decreased in the Rap group, the differences were statistically significant (P<0.05).3. Compared with the CON group, The expression of apoptosis-related protein, Bax and Bax/Bcl-2ratio were increased and the expression of Bcl-2was decreased in hippocampus of the DM group, the differences were statistically significant (P<0.05); Compared with the DM group, the expression of apoptosis-related protein, Bax and Bax/Bcl-2ratio were decreased and the expression of Bcl-2was increased in hippocampus of the Rap group, the differences were statistically significant (P<0.05).Conclusion:In the mode of STZ-induced diabetic mice, rapamycin improve diabetes cognitive dysfunction by inhibiting the progress of neuron cell apoptosis in hippocampus.