α-硫辛酸对链脲菌素诱发的大鼠胰岛β细胞损伤的保护作用

Protective effects of alpha-lipoic acid against beta.cell damage in streptozotocin induced diabetes in rats

目的研究α-硫辛酸（ALA）对链脲菌素（STZ）诱导的糖尿病大鼠胰岛β细胞损伤的保护作用。方法30只SD大鼠按数字随机法分为正常对照组（NC组）、STZ组和ALA＋STZ组（ALA组），各10只。后2组以STZ（70mg／kg体重）一次性腹腔内注射诱发糖尿病，ALA组在注射前8d开始给予ALA（50mg·kg^-1·d^-1，强饲）直至实验结束（4周）。STZ注射后每3天监测血糖、体重一次。测定胰腺匀浆中丙二醛（MDA）含量及还原型谷胱甘肽（GSH）水平，免疫组化方法检测胰岛β细胞内胰岛素水平。结果STZ使大鼠血糖明显升高，STZ和ALA组制模成功率分别为90％（9／10）和70％（7／10），相差显著（P〈0．05）。实验结束时NC组、STZ组和ALA组平均体重分别为（368±3）g、（301±2）g和（341±26）g，3组间相差显著（P〈0．05）。STZ组胰腺组织内MDA水平为（1．22±0．14）nmol／mg prot，NC组为（0．57±0．04）nmol／mg prot，相差显著（P〈0．05）；STZ组胰腺组织内GSH含量为（16．54±1．10）mg／g prot，NC组为（25．46±0．62）mg／g prot（P〈0．05）；STZ组胰岛细胞呈退行性变。ALA组血糖较STZ组明显降低（P〈0．05），胰腺组织匀浆MDA含量为（0．72±0．23）nmol／mg prot，较STZ组明显降低（P〈0．05），GSH含量为（35．33±2．66）mg／g prot，较STZ组明显升高（P〈0．05），胰岛的胰岛素分泌增强，较STZ组显著（P〈0．05），胰岛β细胞损伤减轻。结论ALA可通过减轻氧化应激来保护胰岛β细胞结构和功能的完整性。

Objective To investigate the protective effects of alpha-lipoic acid （ALA） against betacell damage in streptozotocin （STZ）-induced diabetes in rats. Methods Thirty SD rats were randomly divided into three groups： normal control （NC） group, STZ group and ALA ＋ STZ group, with 10 rats in each group. ALA （50mg · kg^-1· day^-1 , oral gavage） was given for 8 days prior to induction of diabetes with STZ （70 mg/kg, intraperitoneal injection）, till the end of the study （4 weeks later）. Blood glucose were measured every 3 days after STZ injection. Malondialdehyde （MDA） and reduced glutathione （GSH） levels were measured in pancreatic homogenates. Pancreatic beta-cells were examined by immunohistochemical methods. Results STZ induced a significant increase of the level of blood glucose. Body weight of rats in ALA ＋ STZ group was （341 ±26）g, which significantly lower than （368 ±3）g in NC group, and high than （301 ±2）g in STZ group with stas（P 〈 0.05 ）. Meanwhile the MDA levels in STZ group and NC group were（ 1.22 ± 0.14） and（0.57 ± 0.04）nmol/mg prot, respectively, and there was significant difference between the two groups （ P 〈 0.05 ） ; the GSH levels in STZ group and N C group were （ 16.54 ± 1.10 ） and （ 25.46 ± 0.62 ） mg/g prot （ P 〈 0.05 ） , respectively ; degeneration of islet cells and decreased blood glucose were observed in STZ ＋ ALA-pretreated rats; MDA level in pancreatic homogenates was （0.72 ± 0.23 ） nmol/mg prot, which was significantly lower than that in STZ group （ P 〈 0.05 ） ; the GSH level was （ 35.33 ± 2.66 ） mg/g prot, which was significantly higher than that in STZ group （ P 〈 0.05 ） ; increased staining of insulin and preservation of islet cells functions were more obvious in the STZ ＋ ALA-pretreated rats. Conclusions ALA exerted its protective effect through reducing the oxidative stress and preserving pancreatic beta-cell integrity.