| Objective To observe the protection of the angiotensin II receptor blockers telmisartan on the cognitive function in diabetic rats.Methods The male Wistar rats (weight 200士20 g) were randomly divided into the normal control group, diabetic model group and the telmisartan treatment group. Streptozotocin-diabetic rat model was induced by a single intraperitoneal injection of STZ at a dose of 65 mg.kg-1.The telmisartan treatment group diabetic rats were treated with intragastric administration of telmisartan (13.3 mg.kg-1.day-1)from onset of diabetes for 12 weeks. After 12 weeks of diabetes,the learning and memory abilities of rats were tested with the Morris water maze and depressive disorder was excluded in Open-Field test. Transmission electron microscope was used to observe synapse ultrastructure in hippocampal CA1 area. the mRNA level and protein level of synaptophysin in hippocampus were detected by RT-PCR and immunohistochemical method.Results In open-Field test, the differences of results among groups were not statistically significant(P>0.05).In Morris water maze, Compared with the normal control group , diabetic model group showed the escaping latency was prolonged(P<0.05) and percentage of stay time in the central area and the frequency of passing the original platform position decrease(P<0.05).Compared with diabetic model group, the telmisartan treatment group showed a significant decrease in the mean time of escape latencies (P<0.05) and an increase of percentage of stay time in the central area and the frequency of passing the original platform position. Under Electron microscope, in hippocampal CA1 area of diabetic model group, mitochondria swelled, the synapses degenerated, presynaptic membrane and postsynaptic membrane were unclear, the numbers of synaptic vesicles decreased, synaptic clefts were narrowed and chondriosomes were swell. Compared with diabetic model group, hippocampal synapse structure of the telmisartan treatment group improved. Compared with the normal control group, the protein expression of synaptophysin in immunohistochemical detection and the level of synaptophysin mRNA in RT-PCR were decreased significantly in diabetic rats hippocampus (P<0.05).The protein expression of synaptophysin in immunohistochemical detection and the level of synaptophysin mRNA in RT-PCR were elevated significantly in hippocampus of the telmisartan treatment group (P<0.05).Conclusion The changes of synapse ultrastructure and the expression of synaptophysin in hippocampus may related to cognitive dysfunction in diabetic rat.In conclusion, Morris water maze performance and hippocampal synapse were impaired in diabetic rats. Telmisartan early treatment can partially improve deficits in Morris maze performance and hippocampal synapse.
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