Effects Of Polygonum Multiflorum Thunb On Cognitive Function And Histological Structure In Diabetic Rats And The Possible Cerebrum Mechanism Involved

Objective: The purpose of this study is to explore the effects of Polygonum multiflorum Thunb on cerebrum cognitive function and histological structure in rats with diabetes mellitus by the examination of expression of MLCK,NR2 B,CaMKⅡ and p-CaMKⅡ,the concentration of Ca2+ in hippocampus and the ultrastructural changes of neurons.Methods: 1.The rat model with diabetes mellitus was established by STZ injecting.Then the diabetic rats were randomly divided into four groups: model group(n=15),polygonum multiflorum low dose group(n=15),polygonum multiflorum high dose group(n=15),insulin group(n=15).The normal matched rats were taken as control group(n=15).From the 4th week to the 12 th week,the diabetic rats in group polygonum multiflorum low dose group(1g/kg/d),and polygonum multiflorum high dose group(2g/kg/d)were treated with the extract of Radix Polygoni Multiflori and insulin separately(8U/kg,2 times /day).Fasting blood glucose was monitored by blood glucose meter.2.Cognitive function of all rats was detected by Morris water maze test.3.The ultrastructure of hippocampal neurons were observed by transmission electron microscope.4.The change of Ca2+concentration in hippocampal neurons was detected by flow cytometry(Fluo-3/AM).5.The expressions of MLCK,NR2 B,CaMKⅡ and p-CaMKⅡ in hippocampus were detected by western blot.Results:1.Compared with the diabetic model group,the blood glucose was significantly decreased in the Polygonum multiflorum and insulin intervention groups(P<0.01).2.Compared with the normal control group,the escape latency was significantly prolonged(P<0.01)and the crossing the platform was significantly reduced in diabetic model rats(P<0.01);compared with the diabetic model group,the escape latency was significantly shorten(P<0.01)and the crossingthe platform was significantly increased(P<0.01)after the intervention of high-dose Polygonum multiflorum and insulin intervention,but there was no significant difference in low dosage group of Polygonum multiflorum Thunb(P>0.05).3.Compared with the control group,the neurons in diabetic model group were irregular in morphology,and the number of neurons and synapses decreased significantly;Compared with the diabetic model group,the morphology and structure of neurons were more complete,and the number of neurons and synapses were significantly increased after Polygonum multiflorum and insulin intervention.4.Compared with the control group,the concentration of Ca2+ and the expression of MLCK and NR2 B in hippocampus were significantly increased in the diabetic model group(P<0.01);compared with the diabetic model group,the concentration of Ca2+ and the expression of MLCK and NR2 B in hippocampus were significantly decrease(P<0.01)in Polygonum multiflorum high dose group and insulin group;the concentration of Ca2+were significant increased(P<0.01)and the expression of MLCK and NR2 B were no significant decreased(P>0.05)in hippocampus in Polygonum multiflorum low dose group.5.Compared with the control group,the expression of p-CaMKⅡ in hippocampus of diabetic rats were significantly decreased(P<0.05);Compared with the diabetic model group,the level of p-CaMKⅡ in hippocampus was significantly decreased after the intervention of Polygonum multiflorum Thunb,but there was no significantly increased in the insulin group.And there was no significant difference in the expression level of CaMKⅡ among the every groups.Conclusion: 1.Radix polygoni Multiflori and insulin may protect the neurons and synapses structure and improve the cognitive dysfunction of diabetic rats 2.The expression of MLCK,NR2 B and the concentration of Ca2+ in neurons was decreased after the intervention of Polygonum multiflorum and insulin.3.The expression of p-CaMKⅡ was decreased in diabetic rats,and it could be improved by Polygonum multiflorum Thunb,but there was no significant change in insulin group.