补肾复方抗老年大鼠肝肾线粒体老化的实验研究

目的 观察补肾复方抗老年大鼠肝肾线粒体老化的作用 ,为“肝肾同源”提供实验依据。方法 实验大鼠分青年和老年组 ,其中老年组分空白对照组和补肾复方治疗组。采用荧光光度计测定肝肾线粒体内膜流动性 ,比色测磷法测定肝肾线粒体内膜 ATP酶活力 ,生物组织测氧仪测定肝肾线粒体氧化磷酸化效率 (ADP/ O)及呼吸控制率 (RCR) ,透射电镜观察肝肾线粒体形态及形态计量学分析。结果 老年大鼠肝肾线粒体内膜流动性、ATP酶活力、ADP/ O和 RCR均较青年组明显降低 ,而服用补肾复方 2个月后的老年大鼠上述指标均明显增高 (P<0 .0 5或 P<0 .0 1 ) ;透射电镜形态及形态计量学分析结果表明 ,老年组肝肾线粒体肿胀变性 ,补肾复方治疗后 ,肝肾线粒体超微结构变化得到明显改善 (P<0 .0 5或 P<0 .0 1 )。结论 补肾复方对老年大鼠肝肾线粒体老化的结构和功能均有一定的防护 ,线粒体可能是“肝肾同源”的重要物质基础之一。

关注线粒体老化在缺血性脑损害中的作用

随着人口老龄化进程的不断加速,脑血管疾病的发病率快速增长,增龄性相关线粒体老化在神经系统疾病中的作用越来越受到关注。生理性线粒体老化是缺血性脑损伤的重要机制之一,而脑缺血又可加速病理性线粒体老化的进程,二者相互促进,形成恶性循环,对缺血性脑损害及其相关卒中后认知功能受损可能具有重要意义。因此,本文针对缺血性脑损害线粒体老化现象,揭示可能的脑血管病相关致病机制和探寻卒中防治策略提供新思路。

大鼠脑线粒体老化的生物学特征

既往研究表明,线粒体的老化是细胞衰老的重要原因之一。本文观察了不同龄大鼠脑内线粒体自由基水平及膜流动性的变化。 材料和方法 一、实验动物 纯系Wistar大鼠(购自山东省医学实验动物中心),雌雄兼用,不限饮食。动物随机分为幼年组(1月龄)、成年组(4月龄)和老年组(20月龄)。

Mitochondrial redox metabolism in aging:Effect of exercise interventions

Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercise is able to retard the onset and impede the progression of aging by modifying mitochondrial oxidant--antioxidant homeostasis. Here we provide a broad overview of the research evidence showing the relationship between mitochondrial redox metabolism, aging and exercise. We address part aspects of mitochondrial reactive oxygen species （ROS） metabolism, from superoxide production to ROS detoxification, especially antioxidant enzymes and uncoupling protein. Furthermore, we describe mitochondrial remodeling response to aging and exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for redox signaling involved in mitochondrial remodeling and redox metabolism regulation are also reviewed.

Mitochondria and the aging heart

The average human life span has markedly increased in modem society largely attributed to advances in medical and therapeutic sciences that have successfully reduced important health risks. However, advanced age results in numerous alterations to cellular and subcellular components that can impact the overall health and function of an individual. Not surprisingly, advanced age is a major risk factor for the development of heart disease in which elderly populations observe increased morbidity and mortality. Even healthy individuals that appear to have normal heart function under resting conditions, actually have an increased susceptibility and vulnerability to stress. This is confounded by the impact that stress and disease can have over time to both the heart and vessels. Although, there is a rapidly growing body of literature investigating the effects of aging on the heart and how age-related alterations affect cardiac function, the biology of aging and underlying mechanisms remain unclear. In this review, we summarize effects of aging on the heart and discuss potential theories of cellular aging with special emphasis on mitoehondrial dysfunction.

Mitochondrial dysfunction and aging muscle

Mitochondrial dysfunction in aged skeletal muscle has been mainly attributable to mtDNA deletions, uncoupling in oxidative phosphorylation, leading to ATP deficit. Moreover, the accumulation of damaged mitochondria is associated with imperfect autophagocytosis and declined biogenesis of efficient mitochondria. Mitochondria-associated apoptotic signaling is involved in the loss of fibers and atrophy of the remaining fibers by ROS, TNF-α, and denervation, leading to sarcopenia. Current investigations have indicated that exercise, especially resistance exercise, has extensively preventive effects on sarcopenia. Whether caloric restriction in aged animals is suitable for aged people remains to be further clinlically experimented. Additionally, it will be interesting to develop effectively supplementary and alternative medical methods associated with Chinese tonifying herbs to prevent or reverse sarcopenia in the future because of their efficacy and less frequent side effects.

Effects of electroacupuncture on functions of hippocampal mitochondrial respiratory chain in SAMP8 mice

Objective To investigate the mechanism of electroacupuncture （EA） in treating Alzheimer＇s disease （AD） from aspect of mitochondria. Methods Twelve 8-month old SAMP8 mice were randomly divided into a model group （Group Mod, n=6） and an electroacupuncture group （Group EA, n=6）, and six 8-month old SAMR1 mice were selected as a control group （Group Cont）. Animals in Group EA was treated with EA at ＂Baihui＂ （百会 GV 20）, ＂Dazhui＂ （大椎 GV 14）, ＂Shenshu （肾俞 BL 23） and ＂Taixi＂ （太溪 KI 3） for 20 min, once daily with 20 days of treatments as a therapeutic course, lasting for 3 courses. Mice in the other two groups were fixed in the same way as those in Group EA at the same time without any treatment. After treatment, learning and memory abilities of the mice were measured by Morris water maze, activities of enzyme complex of hippocampal mitochondrial respiratory chain were measured by spectrophotometry, and levels of adenosine triphosphate （ATP） were detected by reverse phase high performance liquid chromatography （HPLC） method. Results Compared with Group Cont, the average escape latency in Group Mod was significantly prolonged, the residence time on the platform quadrant was shortened, the activities of enzyme complex Ⅰ, Ⅱ, Ⅲ and Ⅳ in hippocampal mitochondrial respiratory chain was decreased, and ATP contents was lessened in Group Mod. Compared with Group Mod, the average escape latency was significantly shortened, the residence time on the platform quadrant was lengthened, the activities of enzyme complex Ⅰ, Ⅱ, Ⅲ and Ⅳ in hippocampal mitochondria respiratory chain were significantly increased, and ATP contents were also increased in Group EA. Conclusion Electroacupuncture can elevate the activities of enzyme complex in hippocampal mitochondrial respiratory chain and ATP contents, and improve mitochondrial functions, which may be one of the underlying mechanisms of EA in treatment of AD.

Effect of acupuncture on hippocampal mitochondrial proteome expression in SAMP8 mouse model with Alzheimer disease

Objective：To observe the effect of acupuncture on the expression of mitochondrial proteome in hippocampus of senescence-accelerated mouse prone g （SAMPg） mice models with Alzheimer disease （AD）,and to explore the possible protective mechanism of acupuncture on mitochondria.Methods：Sixty 6-month-old male SAMP8 mice were randomly divided into an acupuncture at acupoint group,an acupuncture at non-acupoint group and a model group,20 mice in each group.The 20 male senescence-accelerated mouse/resistance 1 （SAMR1） mice of the same age were used as a normal control group.Shenshu （BL 23）,Baihui （GV 20）,Xuehai （SP 10） and Geshu （BL 17） were selected for acupuncture intervention in acupuncture at acupoint group.After an 8-week intervention,mitochondrial tissues were extracted from the hippocampus.Differentially expressed proteins were identified by subcellular organelle proteomics.Western blot was used to verify the expressions of some related proteins in hippocampal mitochondria.Results：Compared with the model group,there were 13 differentially expressed protein spots in the acupuncture at acupoint group,of which,9 were up-regulated,including neurofilament light polypeptide （NFL）,actin （cytoplasmic 1,database ID：ACTB）,tubulin beta-2A chain （TBB2A）,tropomodulin-2 （TMOD2）,pyruvate dehydrogenase E1 component subunit beta （PDHE1-β）,NADH-ubiquinone oxidoreductase 75 kDa subunit （database ID：NDUS1）,heat shock cognate 71 kDa protein （HSC71）,pyruvate dehydrogenase E1 component subunit alpha （PDHE1-α） and ATP synthase beta subunit （ATP-β）;4 were down-regulated,including glial fibrillary acidic protein （GFAP）,pyruvate dehydrogenase phosphatase 1 （PDP1）,mitochondrial-processing peptidase subunit alpha （MMP-α） and adenosine kinase （ADK）.According to the information provided in the protein database,most of the differentially expressed proteins involve the regulation of mitochondrial function and structure.The expression levels of NFL and TBB2A in the normal control group and the acupuncture at acupoint group were significantly higher than those in the acupuncture at non-acupoint group （P〈0.05）.ATP-β and NDUS1 expression levels were significantly higher in the acupuncture at acupoint group than those in the acupuncture at non-acupoint group （P〈0.05）;there was no significant difference between the acupuncture at non-acupoint group and the model group （P〉0.05）.Conclusion：Acupuncture may achieve the potential therapeutic effect on AD by regulating the structure and functional proteins of hippocampal mitochondria.