The Study Of Cannabinoid CB1 Receptor Expressed In The Hippocampus Of Streptozotocin-induced Diabetic Rats

ObjectivesDiabetes mellitus is the most common metabolic disorder in human being,and it is the crucial killer which threaten the life of Chinese people.Diabetes mellitus affects many tissues and organs,including the brain.Cognitive deficits is the main clinical manifestation of the central nervous system complication of diabetic mellitus—"diabetic encephalopathy",which is gradually thought highly of by the medical science,though its pathogenesis still remains unknown.CB1Rs are ubiquitously expressed in the brain,where they are mostly located presynaptically in a wide range of neurons.In particular,they are highly abundant in the human and the rodent hippocampus.It is reported that in several brain areas including the hippocampus, CB1Rs has been shown to modulate glucose utilization.In other words,CB1Rs are intricately involved in a wide spectrum of physiological and pathological mechanisms that are affected in diabetic encephalopathy.Thus,the study is aimed to test whether the density and the expression of CB1Rs receptor is changed in a classic animal model of T1D,and if glutathione(GSH)is effective to its expression,and if GSH is affected the blood glucose of the T1D rats.Materials and Methods30 Wistar rats were randomly divided into diabetes mellitus group and glutathione therapy group and normal group.There are 10 rats in each group.Rats of diabetes mellitus group(DM group)and glutathione therapy group(GSH group)were injected intraabdominal with Streptozocin(STZ)to make experimental diabetes mellitus models.The rats of DM group were treated without any medical managements,and the GSH group were treated with reduced GSH by intraabdominal injection,according to the dose of 0.1g/100g/d.Rats of each group were weighted per 2 weeks,and assayed blood glucose per 4 weeks.Rats were sacrificed for removing brains after weighing and assaying blood glucose by the end three months respectively,The expressive change of CB1Rs of neurons of hippocampus were studied by immunohistochemical. All experimental results were statistically analyzed with SPSS10.0.Results1.The general condition Rats of DM group have obvious symptoms of polydipsia and polyuria,with dirty and bloom fur,dispirited and lazy to activity,the blood glucose is remains in high level(17.8～31.1 mmol/L),4 rats died during the experiment; Rats of GSH group have similar symptom,3 rats died during the experiment(the dead rats were not included in the statistics);while the rats of normal group have no diabetic symptom,have a good condition of growth and nutrition. 2.The weight and blood glucose The weight and weight increasing per 2 weeks of each group,the DM group were(342.7±16.28)g and(25.72±4.45)g,the GSH group were(353.1±11.95)g and(28.35±4.97)g,the NC group were(410.3±6.20) g and(36.77±4.31)g;the blood glucose of every period of the DM group were (24.31±3.86)(24.8±4.17)(23.69±7.49)(22.57±6.32)mol/L,the GSH group were (23.59±4.03)(22.91±7.65)(21.15±7.41)(17.76±8.31)mol/L,the NC group were (5.73±0.62)(5.92±0.81)(5.84±0.82)(5.55±0.59)mol/L;Compared to the NC group,weight and blood glucose of the DM group and GSH group have significant difference(P<0.01),while the difference between the DM group and GSH group was not significant(P>0.05);the blood glucose of three rats in the GSH group decreased to normal range while there is only one rat in the DM group.3.The immunohistochemistrical staining of the region of CA2 of the hippocampus It is showed that each group has abundant positive neuron in the hippocampus,and there also has weakly positive expression of CB1Rs the synapsis.Compared to the NC group,the positive of CB1Rs neurons in the DM group has significant difference (P<0.05),while in the GSH group has no significant difference(P>0.05).Conclusions1.The density of CB1Rs which expressed in the hippocampus of diabetic rats is higher than the normal rats,and indicate that CB1Rs play a role in the pathogenesis of diabetic encephalopathy2.GSH can downregulate the expression of the CB1Rs in the hippocampus of the diabetic rats.3.GSH doesnot have direct contributions to the blood glucose of the diabetic rats, but it maybe have mediate effect to the blood glucose by certain mechanisms.