姜黄素对糖尿病脑病大鼠氧化应激及海马iNOS表达的影响

Effect of curcumin on oxidative stress and hippocampus iNOS expression in diabetic encephalopathy rats

目的探讨糖尿病脑病与氧化应激和诱导型一氧化氮合酶(iNOS)的关系,及姜黄素治疗的效果和机制。方法大鼠随机分为正常对照组(CN)、正常姜黄素组(Cur)、糖尿病组(DM)、糖尿病+姜黄素治疗组(DM+Cur),以注射链脲佐菌素建立糖尿病大鼠模型,Cur组和DM+Cur组采用Cur(60mg·kg-1.d-1)灌胃给药。12周后测定海马组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及丙二醛(MDA)、一氧化氮(NO)含量,RT-PCR和免疫组化方法检测海马iNOSmRNA表达水平及iNOS免疫阳性细胞平均光密度值(MOD)值。结果与CN组相比,DM组海马组织SOD和CAT活性明显降低(P<0.01),NO和MDA含量明显增加(P<0.01),海马组织iNOSmRNA及蛋白表达较CN组明显增加(P<0.01);与DM组相比,DM+Cur组SOD和CAT活性明显增加(P<0.01),NO和MDA含量明显降低(P<0.01),海马组织iNOSmRNA及MOD值明显降低(P<0.01)。结论糖尿病脑病与氧化应激水平及海马组织iNOS表达升高相关;姜黄素可能通过抗氧化活性及下调iNOS表达,而对糖尿病脑病起保护作用。

Objective To investigate the relation of diabetic encephalopathy with oxidative stress and hippocampus expression of inducible nitric oxide synthase（iNOS） in rats and to study the therapeutic effects of curcumin.Methods Diabetes mellitus was induced by injection of Streptozotocin in rats.The experiment animals were randomly divided into control group,diabetic group,diabetes plus curcumin group and control plus curcumin group; animals in the latter two groups received 60 mg·kg^-1·d^-1 curcumin treatment.Superoxide dismutase（SOD）,catalase（CAT）,malondialdehyde（MDA） and nitric oxide（NO） in the hippocampal tissues were measured 12 weeks after treatment.The expression of iNOS mRNA and the mean optical density （MOD） of immunoreactive neurons were evaluated by RT-PCR and immunohistochemistry method,respectively.Results Compared with the control group,diabetic group had significantly lower activities of SOD and CAT,higher contents of NO and MDA,and increased expression of iNOS mRNA and protein in the hippocampal tissues （P〈0.01）.Compared with the diabetic group,diabetic plus curcumin group had significantly higher activities of SOD and CAT,lower contents of NO and MDA and decreased expression of iNOS mRNA and the MOD of immunoreactive neurons in hippocampus （P〈0.01）.Conclusion Diabetic encephalopathy is associated with oxidative stress and increased expression of iNOS; curcumin may protect diabetic encephalopathy by inhibiting oxidative stress and down-regulating the iNOS expression.