戴蒙开颗粒对阿尔茨海默病小鼠脑组织线粒体动力学的影响

Effects of Daimengkai Granule on mitochondrial kinetics in brain tissue of Alzheimer's disease mice

目的:探讨戴蒙开颗粒对阿尔茨海默病小鼠脑组织线粒体动力学的影响。方法:30只APP/PS1小鼠随机分为模型组、戴蒙开颗粒治疗组(中药组),并以15只同月龄同性别的C57BL/6J野生型小鼠作为空白组。中药组给予剂量2.0 g·kg^(-1)·d^(-1)的戴蒙开颗粒0.2 ml灌胃,模型组和空白组给予等体积的0.9%Na Cl溶液灌胃;均灌胃12周。干预结束后,取脑组织分离线粒体,运用Western Blot法检测小鼠脑组织线粒体及去线粒体胞浆动力相关蛋白1(dynamin-related protein1,Drp1)、分裂蛋白1(fission1,Fis1)、视神经萎缩蛋白1(optic atrophy-1,Opa1)和小鼠脑组织NIX蛋白的含量;Elisa法检测小鼠脑组织Bax、Bcl-2蛋白表达。结果:与空白组比较,模型组小鼠脑组织线粒体及去线粒体胞浆Drp1、Fis1、NIX、Bax蛋白含量均明显升高(P<0.01),Opa1、Bcl-2含量则明显降低(P<0.01);与模型组比较,中药组小鼠脑组织线粒体及去线粒体胞浆Drp1、Fis1、NIX、Bax含量明显降低(P<0.05,P<0.01),Opa1、Bcl-2含量明显升高(P<0.01)。结论:戴蒙开颗粒可改善阿尔茨海默病小鼠脑内线粒体分裂融合异常。

Objective: To investigate the effects of Daimengmai Granule on the mitochondrial kinetics in the brain tissue of mice with Alzheimer's disease. Methods: 30 APP/PS1 mice were randomly divided into the model group and Daimengmai Granule( Chinese medicine) group,15 wild type C57 BL/6 J mice with the same age and sex were taken as the blank group. The Chinese medicine group was treated with Daimengmai Granule at dose of 2.0 g·kg^(-1)·d^(-1) by intragastric administration,the model group and blank group were treated with 0.9% Na Cl solution at equivalent volume by intragastric administration,with a course of 12 weeks. After intervention,the brain tissue was collected and the mitochondria were isolated. The protein expressions of dynamin-related protein1( Drp1),fission1( Fis1),optic atrophy-1( Opa1) in post-mitochondrial and mitochondrial cytoplasm of brain tissue and the protein expression of Bcl-2/adenovirus E1 B 19 k Da-interacting protein 3-like( BNIP3 L or NIX) in brain tissue were detected by Western blot. The protein expressions of Bax and Bcl-2 in brain tissue were detected by ELISA. Results: Compared with the blank group,the protein expressions of Drp1 and Fis1 in postmitochondrial and mitochondrial cytoplasm of brain tissue and protein expressions of NIX and Bax in brain tissue were obviously increased in the model group( P<0.01),and the expressions of Opa1 and Bcl-2 were obviously decreased( P < 0. 01). Compared with the model group,the protein expressions of Drp1,Fis1,NIX and Bax in brain tissue were obviously decreased in the Chinese medicine group( P <0.05,P < 0.01),and the expressions of Opa1 and Bcl-2 were obviously increased( P < 0. 01). Conclusion: Daimengkai Granule can improve the mitochondrial splitting and fusion abnormality in the brain of mice with Alzheimer's disease.