Effects Of Angiotensin-(1-7) On The Expression Of GFAP And GDNF In Hippocampus And Cognitive Function Of Rats With Diabetes Mellitus

PART ONE EFFECTS OF ANGIOTENSIN(l-7) ON THE EXPRESSION OF GFAP IN HIPPOCAMPUS AND COGNITIVEFUNCTION OF RATS WITH DIABETES MELLITUSObjective:To investigate the effects of angiotensin(1-7) on the learning and memory and expression of glial fibrillary acidic protein (GFAP) in hippocampus of diabetic mellitus rats.Methods:Forty male SD rats were randomly assigned to four groups: normal control group (NC group), diabetic group (DM group),Ang(1-7)-treated diabetic group (DM1 group), [Ang-(1-7) and Mas receptor antagonist [D-Ala7]-Ang(1-7)(A779)]-treated diabetic group (DM2 group). Streptozotocin-induced diabetic rats by a single intraperitoneal injection.Learning and memory function of rats were measured by the Morris water maze (MWM) test. Morphological changes were examined with Nissl staining. Expression of GFAP in the hippocampus was assessed by immunohistochemistry.Results:Compared with NC group,learning and memory function of DM group rats impaired significantly (P<0.05), The expression of GFAP was decreased in hippocampus(P< 0.05), significant hippocampal neuronal injury was observed.After treament with Ang(1-7), learning and memory of DM1 rats was improved (P< 0.05),the expression of GFAP was increased (P< 0.05), the number of neuron survival was increased.The effects of Ang(1-7) in hippocampal region were blocked when diabetic animals treated with a combination of Ang(1-7) and A779.Conclusions:1.SD rats showed cognitive dysfunction after chronic hyperglycemia 12 weeks, hippocampus neuron was impaired and the expression of GFAP decreased obviously.2.Ang(1-7) could alleviate the cognitive dysfunction of diabetic rats by increasing the expression of GFAP and reducing the neuron damage.PART TWO EFFECTS OF ANGIOTENSIN-(1-7) ON THE EXPRESSION OF GDNF AND CASPASE-3 IN HIPPOCAMPUS AND COGNITIVE FUNCTION OF RATS WITH DIABETES MELLITUSObjective:To explore the effects of Ang(1-7) on the expression of glial cell line-derived neurotrophic factor (GDNF) and caspase-3 in hippocampus of diabetic mellitus rats.Methods:Forty male SD rats were randomly assigned to four groups: normal control group (NC group), diabetic group(DM group),Ang(1-7)-treated diabetic group (DM1 group), [Ang-(1-7) and Mas receptor antagonist [D-Ala7]-Ang(1-7)(A779)]-treated diabetic group (DM2 group). Streptozotocin-induced diabetic rats by a single intraperitoneal injection (60mg/kg).Cognitive function of rats was measured by MWM test.The level of GDNF in the hippocampus was assessed by RT-PCR and western blot,respectively.The expression of caspase-3 was examined by immunohistochemistry.Results:Compared with NC group,learning and-memory level of DM group rats impaired significantly (P<0.05), the expression of GDNF mRNA and protein level was decreased in hippocampus(P< 0.05), but the expression of caspase-3 was obviously increased (P< 0.05).After treament with Ang(1-7), learning and memory level of diabetic rats was improved (P < 0.05),the expression of GDNF was increased (P< 0.05), the expression of caspase-3 was decreased in hippocampal region of rats (P< 0.05).Ang(1-7) effect in hippocampal region was blocked when diabetic animals that were treated with a combination of Ang(l-7) and A779.Conclusions:1.SD rats showed cognitive dysfunction after chronic hyperglycemia 12 weeks, GDNF and caspase-3 in hippocampal may be involved in the progression of diabetic encephalopathy;2.Ang(1-7) could alleviate the diabetic cognitive dysfunction of rats, its neuroprotection may be associated with upregulation of GDNF and downregulation of caspase-3 expression.