摘要
目的探讨左归丸对自然衰老大鼠中枢神经线粒体能量代谢及结构的改善作用及其机制。方法40只SD大鼠随机分为对照组、左归丸组。经灌胃给予左归丸60d后,采用Morris水迷宫实验检测左归丸对自然衰老大鼠学习记忆能力的影响;高效液相色谱法(HPLC)检测自然衰老大鼠脑组织中三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、单磷酸腺苷(AMP),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)活性及线粒体膜电位;Western印迹检测过氧化物酶体增殖物活化受体γ协同刺激因子(PGC)-1α蛋白的表达。结果左归丸可以显著改善自然衰老大鼠学习记忆能力,与对照组比较,左归丸组脑组织ATP和EC水平显著升高(P<0.01),PDH和KGDH活性显著升高(P<0.01),线粒体膜电位及PGC-1α蛋白表达显著升高(P<0.01)。结论左归丸能通过保护线粒体能量代谢及其膜结构,改善大脑神经元细胞功能,进而提高自然衰老大鼠学习记忆能力,这可能与促进PGC-1α通路的表达有关。
Objective To investigate the effect of Zuoguiwan on mitochondrial energy metabolism and the underlying mechanism in central nerve of 24-months aging rat model.Methods Totally 40 male rats were randomly distributed into control and Zuoguiwani groups(12.12 g/kg).After administrated with Zuoguiwan via intragastric gavage for 60 days,Morris water maze test were performed to evaluate the effect of Zuoguiwan on the learning and memory ability of aging rats;to test the levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP),adenosine monophosphate(AMP)with HPLC,then energy charge(EC)was calculated to evaluate the enzymatic activity of pyruvate dehydrogenase(PDH),α-ketoglutarate dehydrogenase(KGDH)and mitochondrial membrane potential(MMP)with spectrophotometry;peroxisome proliferator activated receptorγcoactivator(PGC)-1αwere determined by Western blot.Results It was found that Zuoguiwan could improve the learning and memory ability of aging rats significantly.The levels of ATP and EC were promoted(P<0.01).The PDH and KGDH,two key enzymes in tricarboxylic acid cycle(TCA)were activated(P<0.01),MMP were elevated(P<0.01),the expression of PGC-1αwere significantly up-regulated in aging rats with Zuoguiwan treatment.Conclusions Zuoguiwan could protect the structure and function of mitochondria in central nerve of aging rats,improve the energy metabolism as well as the learning and memory ability of aging rat,these changes could be due to the activation of the PGC-1αpathway.
作者
赵新永
李晓婷
周飞
ZHAO Xin-Yong;LI Xiao-Ting;ZHOU Fei(The Medical School,Zhengzhou University of Chinese Industrial Technology,Zhengzhou 451150,Henan,China)
出处
《中国老年学杂志》
CAS
北大核心
2019年第15期3722-3725,共4页
Chinese Journal of Gerontology
基金
国家自然科学基金项目(81573722)
