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小檗碱对链脲佐菌素和高碳水化合物/高脂肪饮食诱导的糖尿病大鼠β细胞的保护作用。

Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats.

作者信息

Zhou Jiyin, Zhou Shiwen, Tang Jianlin, Zhang Kebin, Guang Lixia, Huang Yongping, Xu Ying, Ying Yi, Zhang Le, Li Dandan

机构信息

Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, PR China.

出版信息

Eur J Pharmacol. 2009 Mar 15;606(1-3):262-8. doi: 10.1016/j.ejphar.2008.12.056. Epub 2009 Jan 19.

Abstract

Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Berberine is one of the main alkaloids of Rhizoma coptidis which has been used to treat diabetes for more than 1400 years in China. The present study was designed to evaluate the protective effects of berberine against beta cell damage and antioxidant of pancreas in diabetic rats. Diabetic rats with hyperlipidemia were induced by intraperitoneally injection 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Rats were divided into 7 groups at the end of week 16: untreated control, untreated diabetic, 75, 150, 300 mg/kg berberine-treated diabetic, 100 mg/kg fenofibrate-treated, and 4 mg/kg rosiglitazone-treated. After 16 weeks treatment, serum insulin level, insulin expression in pancreas, and malonaldehyde content, superoxide dismutase activity in pancreatic homogenate were assayed. Pancreas was examined by hematoxylin/eosin staining and transmission electron microscope. Pancreas to body weight ratio, insulin level, insulin sensitivity index, malonaldehyde content and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with 150, 300 mg/kg berberine. Mitochondrial vacuolization and swelling, dilatation of the endoplasmic reticulum were observed in beta cells of diabetic rats. The pancreatic islet area atrophied and secretory granules of beta cells decreased in diabetic rats. Slight pathological changes existed in beta cells of 150, 300 mg/kg berberine-treated diabetic pancreas. These findings suggest that berberine has protective effect for diabetes through increasing insulin expression, beta cell regeneration, antioxidant enzyme activity and decreasing lipid peroxidation.

摘要

糖尿病中的氧化应激与抗氧化状态降低并存,这会进一步增加自由基的有害影响。黄连素是黄连的主要生物碱之一,在中国已被用于治疗糖尿病1400多年。本研究旨在评估黄连素对糖尿病大鼠胰岛β细胞损伤的保护作用以及胰腺的抗氧化作用。通过腹腔注射35mg/kg链脲佐菌素和高碳水化合物/高脂肪饮食诱导患有高脂血症的糖尿病大鼠。在第16周结束时,将大鼠分为7组:未治疗的对照组、未治疗的糖尿病组、75mg/kg、150mg/kg、300mg/kg黄连素治疗的糖尿病组、100mg/kg非诺贝特治疗组和4mg/kg罗格列酮治疗组。治疗16周后,检测血清胰岛素水平、胰腺中胰岛素表达、丙二醛含量、胰腺匀浆中超氧化物歧化酶活性。用苏木精/伊红染色和透射电子显微镜检查胰腺。糖尿病大鼠的胰腺与体重比、胰岛素水平、胰岛素敏感性指数、丙二醛含量和超氧化物歧化酶活性发生改变,而用150mg/kg、300mg/kg黄连素治疗后接近对照水平。糖尿病大鼠的胰岛β细胞中观察到线粒体空泡化和肿胀、内质网扩张。糖尿病大鼠的胰岛萎缩,胰岛β细胞的分泌颗粒减少。150mg/kg、300mg/kg黄连素治疗的糖尿病胰腺的胰岛β细胞存在轻微病理变化。这些结果表明,黄连素通过增加胰岛素表达、胰岛β细胞再生和抗氧化酶活性以及减少脂质过氧化对糖尿病具有保护作用。

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