地黄饮子对AD大鼠中枢神经线粒体结构及功能的保护作用

Effect of Dihuang Yinzi on Mitochondrial Structure and Function in Central Nerve of Alzheimer’s Disease Rats

目的：以侧脑室注射β-淀粉样蛋白1-42（Aβ1-42）致痴呆大鼠为阿尔茨海默病（AD）模型,探讨地黄饮子对AD大鼠中枢神经线粒体结构功能损伤的保护机制。方法：120只SD大鼠随机分为假手术组,模型组,阳性药（安理申,0.5 mg·kg（-1））组,地黄饮子高、中、低剂量组（3,1.5,0.75 g·kg（-1））。除假手术组外,其他大鼠均在左侧脑室注射老化的Aβ1-42建立AD大鼠模型。经灌胃给予地黄饮子30 d后,采用Morris水迷宫和跳台实验检测地黄饮子对AD大鼠学习记忆能力的影响,高效液相色谱法检测AD大鼠脑组织中三磷酸腺苷（ATP）,二磷酸腺苷（ADP）,单磷酸腺苷（AMP）,磷酸肌酸（PCr）,并计算能荷（EC）水平,光吸收法检测线粒体中丙酮酸脱氢酶（PDH）和α-酮戊二酸脱氢酶（KGDH）活性、线粒体肿胀度、膜电位等。结果：地黄饮子可以显著改善AD大鼠学习记忆能力,与模型组比较,地黄饮子升高大鼠脑组织ATP,ADP,PCr及EC水平（P〈0.05,P〈0.01）,升高三羧酸循环关键酶PDH和KGDH活性（P〈0.05,P〈0.01）,降低线粒体肿胀程度（P〈0.05,P〈0.01）,升高线粒体膜电位（P〈0.05,P〈0.01）。结论：地黄饮子药能通过保护线粒体结构功能,改善能量代谢,提高AD大鼠学习记忆能力。

Objective： To investigate the effect of Dihuang Yinzi on mitochondrial structure and function in central nerve of Alzheimer＇s disease（ AD） rat model induced by intracerebroventricular injection of β-amyloid protein 1-42（ Aβ1-42）. Method： Totally 120 male rats were randomly distributed into 6 groups： shame operation group,AD model group,positive drug control group（ Aricept,0. 5 mg·kg（-1））,high-,moderate-and low-dosage Dihuang Yinzi groups（ 3,1. 5,0. 75 g·kg（-1））. Except for sham operation rats,all the other rats were injected with maturated Aβ1-42 at left lateral ventricles to establish AD rat model. After administrated with Dihuang Yinzi via intragastric gavage for 30 days,Morris water maze and step-down test were performed to evaluate the effect of Dihuang Yinzi on the learning and memory ability of AD rats; the levels of adenosine triphosphate（ ATP）,adenosine diphosphate（ ADP）,adenosine monophosphate（ AMP） and creatine phosphocreatine（ PCr） were determined with high performance liquid chromatography（ HPLC）,then energy charge（ EC） was calculated; the enzymatic activity of pyruvate dehydrogenase（ PDH） and α-ketoglurate dehydrogenase（ KGDH）,mitochondria swelling and mitochondrial membrane potential were evaluated with spectrophotometry. Result： It was found that Dihuang Yinzi could improve the learning and memory ability of AD rats significantly,and promote the levels of ATP,ADP,PCr and EC（ P 〈 0. 05,P 〈 0. 01）. The key ezymes,PDH and KGDH,in tricarboxylic acid cycle were activated（ P 〈 0. 05,P 〈 0. 01）,the mitochondria swelling was mitigated（ P 〈 0. 05,P 〈 0. 01）,and the mitochondrial membrane potential were elevated（ P 〈 0. 05,P 〈 0. 01） in AD rat with Dihuang Yinzi treatment.Conclusion： It was demonstrated that Dihuang Yinzi could protect the structure and function of mitochondria in central nerve of AD rats,improve the energy metabolism as well as the learning and memory ability in AD rats.