The Study Of Protective Effect And Mechanism Of Curcumin On Diabetic Encephalopathy Rats

Background:Recent studies have shown that diabetes is associated with gradually developing damage in the central nervous system by glucose metabolic disorders. This relatively neuronal damage can be referred to as diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities. However, the pathogenesis is not still explicit. Oxidative stress plays a central role in diabetic tissue damage, causing to brain morphological abnormalities and memory impairment. Nitric oxide(NO)is an important endogenous free radical gas, as a neurotransmitter involved in many physiological functions. One of the purposed mechanisms is that NO pathway may be involved in the pathogenesis of diabetic cognitive dysfunction through promoting oxidative stress. At present, there is not effective treatment on prevention and treatment of diabetic encephalopathy. So it is of great significance to study the mechanism and find effective drugs for treatment.Curcumin what a yellow phenolic mpound present in turmeric, is known to many pharmacological activities including hypolipidemic, antioxidant, anti-inflammatory, scavenging free radicals, anti-tumor, anti-microbial, and so on. Recent studies have found that curcumin can protect the nerve and play a protective role in diabetic encephalopathy, but its precise mechanism has not been reported.To this end, we designed the study: we induced diabetic model by a single intraperitoneal injecticn of streptozoticin (STZ) to observe the effect of curcumin on cognitive function in diabetic encephalopathy rats and its mechanism of protection, to provide experimental basis for the clinical application.Objectives:To observe the effect of curcumin on basic conditions, pathological changes in hippocampus, oxidative stress and the expression of NOS, so as to estimate the effect of curcumin on cognitive function in diabetic encephalopathy rats and its mechanism of protection.Methods:Streptozotocin was injected to induce diabetes mellitus. Rats were randomly divided into control group(CN), diabetic group(DM), diabetic treated with curcumin group(DM.Cur) and control treated with curcumin group(CN.Cur). After 12 weeks of treatment, the body weight,blood glucose and cognition ability (examined by Morris water maze test) were valued. The activities of superoxide dismutase(SOD), catalase(CAT), malondialdehyde(MDA) and nitric oxide(NO) were measured in hippocampal tissues by chromatometry. The expression of nNOS and iNOS mRNA and the mean optical density(MOD) of immunoreactive neurons were evaluated by RT-PCR and immunohistochemistry method.Results:1.Compared with CN group, a significant decline in body weight and rise in blood glucose in DM and DM.Cur groups (p<0.05).There was no significant difference (P>0.05) between the DM and DM.Cur groups. Curcumin per se had no effect on body weight and blood glucose.2.Compared with CN group, the escape latency was significantly longer in DM group (P<0.01). Compared with DM group, the escape latency was significantly shorter in DM.Cur group (P<0.05 or 0.01). However, curcumin per se had no effect on cognition.3.The neurons of the hippocamp CA1 were normal morphology in NC group by HE staining.The neurons in DM group were structural disorganized , disordered, swelling or shrinkage of cell body and reduction in the number of neurons, with glial cell proliferation. Curcumin significantly reduced the pathological changes in DM.Cur group. However, curcumin per se had no effect on the morphology of hippocampal neurons.4.Compared with CN group, the activities of SOD and CAT were reduced but the level of MDA and NO was increased significantly in DM group (P<0.01). The activities of SOD and CAT were increased but the level of MDA and NO was decreased significantly in DM.Cur group compared with DM group (P<0.01). However, curcumin per se had no effect on SOD ,CAT activities and MDA ,NO levels.5.Few nNOS positive staining and no iNOS positive staining were found in CN group both in hippocampal CA1 and CA3 regions. Compared with CN group, the MOD of nNOS and iNOS immunoreactive neurons were significantly higher (P<0.01) in DM group.The MOD of nNOS was higher in CA1 than CA3,and the MOD of iNOS was higher in CA3 than CA1 in DM group (P<0.01). Compared with DM group, the MOD of nNOS and iNOS immunoreactive neurons were significantly decreased in DM.Cur group (P<0.01). However, curcumin per se had no effect on the expression of nNOS and iNOS immunoreactivity.6.The expression of nNOS and iNOS mRNA were minor in CN group. Compared with CN group, the expression of nNOS and iNOS mRNA were significantly increased in DM group (P<0.01). Compared with DM group, the expression of nNOS and iNOS mRNA were significantly decreased in DM.Cur group (P<0.01). However, curcumin had no effect on the expression of nNOS and iNOS mRNA.Conclusions:1.Curcumin had no significant effect on body weight and blood glucose, but it can significantly shorten the escape latency in diabetic encephalopathy rats.2.Curcumin can ameliorate the hippocampal CA1 neurons pathological changes of diabetic encephalopathy rats.3.Oxidative stress and increased expression of nNOS and iNOS may be involved in the mechanism of diabetic encephalopathy. Curcumin may protect diabetic encephalopathy by resisting oxidative stress and down-regulating the nNOS and iNOS expression.