衰老细胞的生长抑制因子研究进展

细胞融合实验表明,衰老细胞具有生长抑制活性,细胞衰老是自身基因调控的结果。很多研究者开展了寻找衰老细胞中生长抑制因子的工作,抗癌基因Rb和p53与细胞衰老有密切关系,现综述其研究进展。     

细胞衰老研究进展及意义

细胞衰老是指正常细胞有限增殖特性，有关细胞衰老机制假说主要有二种，一是分子损伤累积假说，二是基因调控假说，许多研究证实细胞衰老具有重要性生物学意义，细胞衰老被认为是机体抗肿瘤形成机制之一，细胞衰老与机体衰老机制相关。     

1型糖尿病大鼠骨髓内皮祖细胞衰老与非对称二甲基精氨酸浓度升高有关

目的研究非对称二甲基精氨酸与1型糖尿病大鼠骨髓内皮祖细胞衰老之间的关系。方法单次腹腔注射链脲佐菌素(65 mg/kg)建立1型糖尿病大鼠模型,检测血糖、骨髓内皮祖细胞衰老、血浆非对称二甲基精氨酸水平以及内皮祖细胞中二甲基精氨酸-二甲胺水解酶2和SIRT1的mRNA表达。结果与对照组比较,糖尿病大鼠血浆非对称二甲基精氨酸水平显著升高(0.67±0.06μmol/L比0.55±0.07μmol/L)、内皮祖细胞衰老率增加(39%±8%比11%±2%)、二甲基精氨酸-二甲胺水解酶(0.56±0.17比1.00±0.22)和SIRT1(0.08±0.17比1.00±0.39)的mRNA表达下调。结论糖尿病大鼠内皮祖细胞衰老与非对称二甲基精氨酸水平升高有关,其机制可能涉及SIRT1/二甲基精氨酸-二甲胺水解酶2途径。     

线粒体氧自由基与衰老的关系

线粒体作为细胞的能源中心,在产生ATP的同时也产生氧自由基,提高细胞的氧化应激水平,从而在细胞衰老中发挥重要作用。本文主要讨论线粒体氧自由基的产生、代谢途径及其随年龄增长而增加的机制,并阐述线粒体内氧自由基增加引起细胞衰老的机制。     

细胞衰老与机体老化关系的研究进展

细胞衰老指细胞从生长状态转变为不可逆转的生长停滞状态。而机体老化通常指生物发育成熟后，在正常情况下随着年龄的增加，功能减退，内环境稳定性下降，结构中心组分退行性变化，趋向死亡的不可逆的状态。近年来随着细胞生物学、分子生物学的发展，对细胞衰老与机体老化的研究发现两者之间有着密切联系。     

DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点,可引起细胞周期停滞、凋亡,加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展,并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系,为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

细胞衰老在糖尿病足溃疡中的研究进展

糖尿病足溃疡在老年糖尿病人群中常见。对糖尿病足溃疡复杂的分子水平机制研究仍在不断探索中, 细胞衰老对糖尿病足溃疡愈合延迟的作用受到关注, 分析细胞衰老与糖尿病足溃疡的关系, 探索细胞衰老延缓糖尿病足伤口愈合的作用机制, 明确清除衰老细胞、延缓细胞衰老的治疗方法, 可为研发糖尿病足溃疡药物提供新的治疗靶点和策略。     

异甘草素通过降低ROS产生抑制顺铂诱导的NRK-52E细胞衰老

目的研究异甘草素对顺铂诱导的大鼠肾小管上皮细胞NRK-52E衰老模型的作用及其机制。方法通过顺铂诱导建立NRK-52E细胞衰老模型:CCK-8法检测不同浓度顺铂处理对NRK-52E细胞活力的影响,β半乳糖苷酶染色检测刺激后细胞衰老水平,实时定量PCR及酶联免疫吸附试验(ELISA)检测衰老相关炎性因子改变,异硫氰酸荧光素标记的膜联素V/碘化丙啶(Annexin V-FITC/PI)染色检测细胞凋亡水平。综合以上多种检测指标后确定顺铂最佳处理剂量。并进一步在建立的细胞衰老模型基础上研究异甘草素的作用:将细胞分为正常对照组、顺铂刺激组、不同剂量异甘草素处理组(5、10、15μmol/L)。检测药物处理后对细胞增殖、凋亡、衰老等的影响,流式细胞术检测细胞内活性氧(ROS)的改变。结果与NC组相比,不同浓度的顺铂均能显著抑制细胞活性,增加细胞衰老程度,促进衰老相关多个炎症因子的分泌,且顺铂浓度为4μmol/L时具有典型的衰老指征,因此,选用其作为后续造模调节;异甘草素处理后,β半乳糖苷酶染色显示衰老细胞数量明显减少,衰老相关炎症因子表达减少,细胞内ROS水平显著降低。结论通过顺铂诱导法可成功建立NRK-52E细胞衰老模型,异甘草素处理可明显改善顺铂诱导的NRK-52E细胞衰老,抑制凋亡,其机制可能与降低ROS水平有关。     

细胞衰老与肾移植

细胞衰老是生物老化进程的重要组成部分。越来越多的研究表明,细胞衰老的两条主要信号通路(p53和p16途径)在肾移植后肾脏病变的发生、发展及预测移植器官预后等方面,起到重要作用。本文简单总结目前关于细胞衰老分子机制方面的研究观点,并就其在肾移植领域的相关研究做一简单综述。     

去乙酰化酶Sirtuins和细胞衰老与动脉粥样硬化的研究进展

细胞衰老是由自身老化或外部刺激诱发的细胞周期停滞。动脉粥样硬化是冠心病的基本病理生理学特征。最新研究发现,细胞衰老是动脉粥样硬化发生发展的重要机制之一。Sirtuins是一类能够调节细胞新陈代谢并参与多种细胞生理功能的去乙酰化酶。以往研究已经揭示了Sirtuins的抗衰老作用,认为Sirtuins是一种与长寿相关的蛋白,可通过调节细胞衰老使动脉粥样硬化得到抑制或逆转。基于此,本文回顾了Sirtuins和细胞衰老与动脉粥样硬化的最新研究发现,并探讨Sirtuins活化作为动脉粥样硬化治疗新靶点的可行性。     

Effect of certain antibiotics of tetracycline series on the level of blood sugar and the role of insulin in the mechanism of its regulation]

Experiments on male rats showed enterally administered tetracycline and chlortetracycline to promote an elevation of the blood sugar level. These antibiotics administered once together with glucose retarded the normalization of the blood sugar concentration. After 7-day administration of tetracycline and chlortetracycline glucose load caused a stable hyperglycemia. Special experiments with depancreatization and insulin injection to the animals and also the intravenous injection of glucose and the antibiotic demonstrated that the changes in the blood sugar concentration under the effect of tetracycline were associated both with its inhibitory action on the absorbing function of the intestine and with the retarded glucose utilization in the tissues. Insulin injected intramuscularly eliminated the hyperglycemic effect caused by the antibiotics.     

The effect of hypophysectomy on the function of the insulin-sensitive central nervous system glucoregulator receptor.

Hypophysectomized and healthy control rats were studied to investigate the mechanism of action of the insulin-sensitive glucoregulator receptor of the central nervous system (CNS). Glucagon-free insulin (500 muU) was injected into the carotid artery, and the peripheral blood glucose was monitored. An immediate significant fall in the blood sugar was observed in intact as well as in hypophysectomized rats. To control these experiments buffer was injected into the carotid artery, or 500 muU insulin was given through the jugular vein of intact and hypophysectomized animals. The systemic blood sugar level remained unchanged for 10-15 min in the control experiments. The results indicate that the function of this insulin-sensitive glucoregulator CNS receptor is not impaired in the hypophysectomized state. The initial phase of its effect, the sudden decrease of the blood sugar level, appears to be independent of pituitary hormone secretion.     

Effect of prolonged feeding of glucose to rats on the levels of sugar and insulin in the blood and the activity of key glycolysis enzymes in the liver]

A study was made of the effect of food with a high glucose content given to albino rats for a long time on blood sugar and insulin. Changes in the activity of hexokinase and pyruvickinase in the liver were also investigated. Food with a high glucose content given to rats for 90--100 days led to an increase in the blood sugar and insulin level. The activity of hexokinase and pyruvickinase rose markedly by the 40th--60th day of feeding, and fell to the initial level by the 80th--90th day. Thus, in case of a prolonged action of insulin on the organism as a result of prolonged stimulation of the insular apparatus of the pancreas by glucose there developed signs of peculiar insulin-resistance.     

Effect of Estradiol and Progesterone Treatment on Carbohydrate Metabolizing Enzymes in Tissues of Aging Female Rats

The aim of this study was to determine the effect of administration of estradiol (E2), progesterone (P4), and combination of estradiol and progesterone (EP) in aging female rats. The changes in the activities of hexokinase (HK), glucose-6-phosphatase (G6P'tase) and glucose-6-phosphate dehydrogenase (G6PDH) enzymes, and in protein levels in tissues of rats namely brain (cerebral hemisphere), heart, liver, kidney and uterus have been measured in different age groups. The random blood sugar level was measured in serum and liver. The different age groups of rats were given 0.1 microg/g body weight estradiol, 2.5 microg/g body weight progesterone and a similar concentration of both in a combined treatment for 1 month. This dose was selected after determining estrogen and progesterone levels in 3 month adult female animals so that the aging female animals had circulating hormone levels nearly the same as those of young female animals. The random sugar level was determined in serum and liver cytosolic fractions, and it was increased by combination treatment. The protein content in tissues showed significant changes only with combined hormone administration when compared with age-matched controls. The activity of HK decreased in aged animals and significantly increased by hormone treatments in all the tissues of the aged rats studied. The activity of G6P'tase increased with age up to 1.5 years and decreased in 2 years. Treatment with E2 and EP further decreased the activity significantly in all the tissues. G6PDH showed a similar pattern as was observed in HK in all the age groups. Therefore, the E2 and EP treatments caused an entire series of growth-related responses, including an increased uptake of glucose, increased the protein level in the tissues of aging rats, thereby reducing the risk factors associated with aging by normalizing hormone levels which decreased with aging and resulted in diseases such as Alzheimer's diseases and diabetes.     

Effect of cogent db,a herbal drug,on plasma insulin and hepatic enzymes of glucose metabolism in experimental diabetes

Aims: The present study was designed to investigate the effect of cogent db, a polyherbal drug on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats.
Methods: Male Wistar rats body weight of 180–200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group: Group 1, normal rats given 2 ml of saline; Group 2, diabetic control rats given 2 ml of saline; Group 3, diabetic rats given aqueous solution of cogent db (0.45 g/body kg weight); and Group 4, diabetic rats given aqueous solution of glibenclamide (600 µg/kg body weight). The treatment was given for 40 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals.
Results: Treatment with cogent db resulted in a significant reduction in blood glucose and the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity were significantly increased in alloxan-diabetic rats.
Conclusions: The present investigation suggests that cogent db controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible because it regulates the activities of hepatic glucose metabolic enzymes.     

Antidiabetic effect of diasulin, a herbal drug, on blood glucose, plasma insulin and hepatic enzymes of glucose metabolism in hyperglycaemic rats

AIM: The present study was designed to investigate the effect of diasulin, a polyherbal drug, on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats. METHODS: Male Wistar rats, body weight of 180-200 g (12 normal and 30 diabetic rats), were used in this study. The rats were divided into seven groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group. Group 1: normal rats given 2 ml of saline; group 2: normal rats given aqueous solution of diasulin (0.20 g/kg of body weight); group 3: diabetic control rats given 2 ml of saline; group 4: diabetic rats given aqueous solution of diasulin (0.05 g/kg of body weight); group 5: diabetic rats given aqueous solution of diasulin (0.10 g/kg of body weight); group 6: diabetic rats given aqueous solution of diasulin (0.20 g/kg of body weight) and group 7: diabetic rats given aqueous solution of glibenclamide (600 micro g/kg of body weight). The treatment was given for 30 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals. RESULTS: Treatment with diasulin resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in plasma insulin and total haemoglobin and a significant improvement in glucose tolerance. Diasulin also resulted in a significant reduction in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity was significantly increased in alloxan diabetic rats. CONCLUSIONS: The present investigation suggests that diasulin, a polyherbal drug, controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible, because it regulates the activities of hepatic glucose metabolic enzymes.     

用高胰岛素-正葡萄糖钳夹实验探讨增龄对Wistar大鼠胰岛素敏感性的影响

目的探讨增龄对Wistar大鼠体重、空腹血糖、空腹胰岛素、空腹游离脂肪酸(FFA)水平及胰岛素敏感性的影响。方法将雄性Wistar大鼠45只分为4月龄组、14月龄组和24月龄组,每组15只,行高胰岛素-正葡萄糖钳夹实验,观察空腹血糖、空腹胰岛素、血清FFA和胰岛素敏感性的变化。结果 3组大鼠的体重差异有统计学意义(P<0.05,P<0.01)。与4月龄组比较,14月龄组和24月龄组大鼠空腹胰岛素、胰岛素抵抗指数明显升高(P<0.01),24月龄组大鼠血清FFA明显高于4月龄组(P<0.01);与4月龄组比较,14月龄组和24月龄组大鼠稳态葡萄糖输注速率明显降低,差异有统计学意义(P<0.01)。多元线性回归分析显示,增龄与胰岛素敏感性呈负相关。结论随着年龄的增加,大鼠空腹血糖无明显差异,空腹胰岛素和FFA均明显增加,胰岛素的敏感性降低,胰岛素抵抗加重。脂肪、肌肉和肝脏可能参与了增龄介导的胰岛素抵抗。     

Inhibition of sucrase by tris in rat and man,demonstrated by oral loading tests with sucrose

In the course of work concerned with the inhibition of small intestinal carbohydrate digesting enzymes, experiments were performed on rats and two healthy volunteers using tris as a sucrase inhibitor. The following results were obtained: (1) Tris does not lower the blood glucose in fasting rats after oral or subcutaneous doses up to 500 mg/kg, when administered as neutral solution (pH 7.0). (2) Tris reduces the glycemia in rats and human subjects after a sucrose load. In addition, the insulinemia caused by administration of sucrose is reduced in man. This smoothing effect on both curves is dose-dependent. A delay of gastric emptying by tris could be excluded. (3) After a glucose or maltose load in rats, tris has no effect on the blood sugar curve. (4) The marked smoothing effect of tris after sucrose loading is probably caused by its well-known in vitro inhibitory effect on intestinal sucrase activity of pigs and humans.     

Effect of aging on the expression of peroxisome proliferator-activated receptor gamma and the possible relation to insulin resistance

BACKGROUND: The morbidity of insulin resistance tends to increase with aging. However, studies on molecular mechanisms underlying insulin resistance in aging process is still in paucity. OBJECTIVE: The effect of aging on peroxisome proliferator-activated receptor gamma (PPARgamma) expression, and in addition, the possible association of PPARgamma expression with insulin resistance in aging process were investigated. METHODS: The minimal model technique (MMT) based on frequently sampled intravenous glucose tolerance test was adopted and SI and glucose effectiveness of young and aged rats were compared. RT-PCR and Western blot were used to determine the expression of PPARgamma at mRNA and protein level in adipose tissue and skeletal muscle, as well as in human colic omentum, respectively. RESULTS: MMT result implied existence of various degrees of insulin resistance in aged rats. The expression of PPARgamma at both mRNA and protein levels in adipose tissue of aged rats dramatically decreased; consequently, the expression of its target gene lipoprotein lipases mRNA also markedly decreased compared with those in young rats. Furthermore, the level of PPARgamma mRNA and glucose transporter-4 mRNA in skeletal muscle of aged rats attenuated significantly. The expression of PPARgamma mRNA in omental adipose tissue of old men was significantly decreased, accompanied by a tendency of higher insulin resistance index, compared with those of the young. CONCLUSION: Aging may be associated with diminished PPARgamma expression affecting insulin resistance in the aged individuals.     

短期和长期热量限制对大鼠胰岛素抗性的影响

研究短期和长期热量限制（caloric restriction,CR）对大鼠胰岛素抗性的影响。结果显示:短期和长期CR鼠显著减轻其肝重、体重;血糖、胰岛素浓度显著低于自由进食（ad libitum,AL）鼠;胰岛素抵抗指数和敏感指数分别显著低于和高于对应的AL鼠。提示短期和长期CR鼠均能适应低浓度的葡萄糖与胰岛素环境,并有效地利用葡萄糖;胰岛素抗性随鼠龄增加而增高,此现象可通过CR而延缓;CR鼠可能由于体脂的减少、运动的增加而增加胰岛素敏感性、降低胰岛素抗性。CR可减轻大鼠的体重,降低血糖、胰岛素浓度,也增强胰岛素敏感性和降低胰岛素抗性。