The Effects Of Angiotensin â…£ On The Cognitive Function Of Diabetic Rats And Its Mechanism

PART ONE EFFECTS OF ANGIOTENSINâ…£ON THE EXPRESSION OF ACETYLTRANSFERASE AND THE COGNITIVE FUNCTION OF DIABETIC RATSObjective: To explore the effects of angiotensinâ…£on the expression of Choline acetyltransferase and its mRNA in hippocampus and cognitive function of diabetic rats.Methods: 52 SD male rats were divided into normal group(group C), diabetic model group(group D) , angiotensinâ…£treatment group(group E) and angiotensinâ…£+ div-AngIV treatment group(group F) randomly . Diabetes was induced by a single peritoneal injection of streptozotocin. 12 weeks later, learning and memory behaviors were investigated using a spatial version of Morris water maze test.Then,Angâ…£was injected into ateral ventricle of group E at a dose of 5nmol(1 nmol/uL) for every rat,once a day lasted for a week.Meanwile, 5nmol(1 nmol/uL) Angâ…£and 5nmol(1 nmol/uL) div-AngIV were injected into group F and normal sodium was injected into group C and group D for a week. Learning and memory behaviors were detected with Morris water maze test again.The expression of Choline acetyltransferase of all rats was examined with immunohistochemical method and its mRNA expression was detected by RT-PCR and in situ hybridization.Result:Compared with group C,group D,group E,group F showed significant increase in the mean time of escape latencies and decrease in percentage of stay time in the central area and the frequency of passing the original platform position in Morris water maze test befoe Angâ…£was injected . Compared with group D,group E showed a decrease in the mean time of escape latencies and an increase in percentage of stay time in the central area and the frequency of passing the original platform position after injecting.These indicators had no improvement in group F compared with group D. Compared with group C,the protein and mRNA expression of ChAT in group D was decreased in immunohistochemical detection and RT-PCR and in situ hybridization.In contrast, the protein and mRNA expression of ChAT was increased in group E.Moreover, the protein and mRNA expression of ChAT in group F had no modification.Conclusion:1. The learning and memory ability of diabetic rats were decreased significantly twelve weeks later . None the less,these indicators were improved after Angâ…£injected.2. The protein and mRNA expression of ChAT in hippocampus of diabetic rats were decreased, but these indicators could be reversed by Angâ…£.3. It is concluded that angiotensinâ…£could improve cognitive ability in diabetic rats by increasing the expression of ChAT and its mRNA levels.PART TWO EFFECTS OF ANGIOTENSINâ…£ON THE HIPPOCAMPUS NEURONAL APOPTOSIS AND THE COGNITIVE FUNCTION OF DIABETIC RATSObjective: To explore the effects of angiotensinâ…£on the hippocampus neuronal apoptosis and the cognitive function of diabetic rats.Methods: 52 SD male rats were divided into normal group(group C), diabetic model group(group D) , angiotensinâ…£treatment group(group E) and angiotensinâ…£+ div-AngIV treatment group(group F) randomly . Diabetes was induced by a single peritoneal injection of streptozotocin.Learning and memory behaviors were investigated by Morris water maze test. Then,Angâ…£was injected into the lateral ventricle of group E at a dose of 5nmol(1 nmol/uL) for every rat,once a day lasted for a week.Meanwile, 5nmol(1 nmol/uL) Angâ…£and 5nmol(1 nmol/uL) div-AngIV were injected into group F and normal sodium was injected into group C and group D for a week. Learning and memory behaviors were detected with Morris water maze test again.The expression of Bcl-xl of all rats was examined with immunohistochemical method.Meanwhile,the hippocampal neuronal apoptosis were measured by TUNEL.Result: Compared with group C, Learning and memory grade and the expression of Bcl-xl and apoptotic neurons in hippocampus in group D have not changes.Compared with group D, Learning and memory grade in the group E were better(P<0.05).The changes of Bcl-xl in hippocampus significantly increased in group E and the number of apoptotic neurons of the hippocampus was decreased remarkably(P<0.05).Conclusion: It is concluded that angiotensinâ…£could improve cognitive ability in diabetic rats by increasing the expression of Bcl-xl to reduce neuronal apoptosis in hippocampus .