5,6-二氢环戊烯并1,2-二硫杂环戊烯-3-硫酮对2型糖尿病大鼠视网膜核因子NF-E2相关因子及血红素氧合酶-1表达的影响  被引量:7

Effect of 5,6-dihydrocyclopenta-1,2-dithiole-3-thione on the expression of nuclear factor erythroid 2-related factor 2 and hemeoxygenase-1 in retina of type 2 diabetic rats

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作  者:田敏[1] 周琦[1] 吕红彬[1] 李友谊[1] 何跃[1] 欧阳科[1] 

机构地区:[1]泸州医学院附属医院眼科,646000

出  处:《中华眼底病杂志》2014年第2期187-192,共6页Chinese Journal of Ocular Fundus Diseases

摘  要:目的 观察Ⅱ相酶诱导剂5,6-二氢环戊烯并1,2-二硫杂环戊烯-3-硫酮(CPDT)对2型糖尿病大鼠视网膜核因子NF-E2相关因子/抗氧化反应元件(Nrf2/ARE)信号通路及氧化应激的影响,探讨CPDT保护糖尿病大鼠视网膜的机制。方法 35只Wistar雄性大鼠随机分为正常组、造模组2个组,造模组中造模成功者再随机分为糖尿病组、CPDT干预组2个组。正常组、造模组分别有8、27只大鼠。糖尿病组和CPDT干预组给予高脂高糖饲料饲养2个月,大鼠空腹12 h后按体重35 mg/kg腹腔注射链脲佐菌素诱导2型糖尿病大鼠模型。CPDT干预组成模后1周开始在高脂高糖饲料中添加CPDT。8周后检测3组大鼠血糖、血清丙二醛(MDA)含量,检测正常组和糖尿病组大鼠血脂含量。逆转录聚合酶链反应检测3组大鼠视网膜Nrf2、血红素氧合酶-1(HO-1) mRNA表达,蛋白免疫印迹法检测Nrf2、HO-1蛋白表达,免疫组织化学法检测Nrf2、HO-1在视网膜的表达。结果 25只大鼠成功建立2型糖尿病大鼠模型,成功率为92.6%。糖尿病组大鼠血脂水平较正常组显著升高(F总胆固醇=65.866,F甘油三酯=25.441,F低密度脂蛋白=38.889,P=0.000)。各组间大鼠血糖值比较,差异有统计学意义(χ^2=25.812,P=0.000),且糖尿病组大鼠血糖显著高于正常组和CPDT干预组。各组间大鼠血清MDA含量比较,差异有统计学意义(F=59.545,P=0.000),糖尿病组大鼠血清MDA高于正常组(t=10.523,P=0.000)和CPDT干预组(t=7.766,P=0.000)。各组大鼠视网膜Nrf2、HO-1 mRNA比较,差异有统计学意义(FNrf2=19.503,PNrf2=0.000;F HO-1=9.737,P HO-1=0.001)。与糖尿病组相比,CPDT干预组大鼠视网膜Nrf2、HO-1 mRNA表达明显增高(tNrf2=3.399,P Nrf2=0.002;tHO-1=2.167,P HO-1=0.039)。各组大鼠视网膜Nrf2、HO-1蛋白比较,差异有统计学意义(FNrf2=112.823,F HO-1=119.361,P=0.000)。与糖尿病组相比Objective To observe the effect of phase Ⅱenzyme inducer 5, 6 -dihydrocyclopenta 1,2-dithiole-3-thione (CPDT) on nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway and oxidative stress in the retina of type 2 diabetic rats. Methods Thirty-five male Wistar rats were randomly divided into two group, normal group and model group. Model group were further randomly divided into two group, diabetic group and CPDT intervention group. There were 8 rats in the normal group and 27 rats in the model group. Diabetic group and CPDT intervention group were given high fat and high sugar diet for 2 months. After 12 hours of fasting, type 2 diabetic rat model was induced by intraperitoneal injection of low dose of streptozotocin. CPDT was added into the high fat and high sugar diets at 1 week after the diabetic model was established in the CPDT intervention group. Eight weeks after CPDT treatment, blood glucose, serum malondialdehyde (MDA), blood lipid [total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C)], Nrf2 and hemeoxygenase -1 (HO-1) expression were evaluated. Results Type 2 diabetic model was successfully established in 25 rats, the success rate was 92.6%.The level of blood lipid of diabetic group was higher than those of the normal group (FTC=65.866,FTG=25.441,F LDLC=38.889;P=0.000). Blood glucose was significant different between all groups (χ^2=25.812,P=0.000), and was significantly higher in diabetic group than that in normal group and CPDT intervention group. The serum MDA content was significant different between all groups (F=59.545,P=0.000), and was significantly higher in diabetic group than that in normal group (t=10.523,P=0.000) and CPDT intervention group (t=7.766,P=0.000). The mRNA level of retinal Nrf2 and HO-1 was significant different between all groups (FNrf2=19.503,PNrf2=0.000; FHO-1=9.737,P HO-1=0.001), and was higher in CPDT intervention group than the diabetic group �

关 键 词:糖尿病视网膜病变 病理生理学 NF-E2相关因子2 血红素氧化酶(脱环) 

分 类 号:R774.1[医药卫生—眼科]

 

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