甲醛对小鼠染色体端粒DNA相对长度的影响

目的 探讨甲醛对小鼠体细胞染色体端粒的损伤.方法 对昆明小鼠灌胃不同剂量的甲醛(10、20、40 mg/kg)连续7d,通过PCR方法检测小鼠血细胞、肝细胞、肾细胞染色体端粒DNA重复序列的相对长度(OD260).结果 与对照组比较,10、20和40 mg,/kg组小鼠的血细胞、肝细胞和肾细胞染色体端粒DNA重复序列缩短,差异有统计学意义(P＜0.05,P＜0.01),且随着甲醛染毒剂量的升高呈缩短趋势.结论 甲醛暴露能破坏小鼠染色体端粒的稳定.     

广西巴马长寿人群外周血白细胞端粒长度检测

目的 比较广西巴马长寿地区与一般地区人群外周血白细胞端粒DNA长度差异,探讨长寿与端粒DNA长度之间可能存在的关系。方法 在广西巴马县长寿村落选取健康个体49人作为长寿组,另选取一般地区健康个体51人作为对照组;运用地高辛探针标记的Southern印迹杂交(Southern blot)方法测量人群外周血白细胞端粒DNA限制性片断(TRF)长度。结果 以年龄为协变量,对长寿组和对照组外周血白细胞端粒DNA长度作协方差分析,长寿组端粒DNA长度(9.29±0.05)kb明显长于对照组(8.48±0.05)kb(P<0.01);长寿组和对照组内,不同年龄段的端粒DNA长度明显不同(P<0.05),端粒DNA长度随年龄的增加而降低。结论 广西巴马长寿地区人群外周血白细胞端粒DNA长度明显长于一般地区人群,提示广西巴马地区人群长寿与其端粒DNA长度较长可能有一定的关系。     

中老年人睡眠与外周血白细胞端粒长度的关联性分析

目的 探索中老年人群睡眠与外周血白细胞端粒长度的关联性,为提倡健康睡眠延缓衰老提供科学依据。方法 使用匹兹堡睡眠质量指数调查表（PSQI）及一般情况调查表,对176名中老年人进行睡眠质量状况调查;采用荧光定量PCR法测量外周血白细胞端粒相对长度,并进行相关和回归分析。结果 外周血白细胞端粒平均长度为（0.995±0.23）T/S,年龄与端粒长度呈负相关（r=-0.241,P=0.003）;睡眠与年龄有关,随着年龄的增加,睡眠质量更差（r=-0.230,P<0.01）、入睡时间更长（r=0.227,P<0.01）、睡眠时间更短（r=-0.486,P<0.01）、睡眠效率更差（r=-0.226,P<0.01）;校正性别、年龄、婚姻、学历、家庭月收入、居住形式、吸烟、饮酒、体育锻炼、基础疾病因素的影响后,线性回归分析显示睡眠时间（β=0.057,P<0.01）、入睡时间（β=-0.046,P<0.01）、睡眠质量（β=0.086,P<0.01）是外周血白细胞端粒长度的独立影响因素,表明睡眠时间越长、入睡时间越短、睡眠质量越好,端粒长度越长。结论 睡眠是影响中老年人群端粒长度的因素,优良的睡眠可能通过减缓端粒长度的缩短延缓衰老,鼓励在社区进行健康睡眠知识的宣教活动,提高睡眠质量。     

不同海拔地区不同年龄组人外周血白细胞端粒DNA长度变化

目的 探讨不同海拔地区不同年龄组人外周血白细胞端粒DNA长度变化.方法 分别选取高原组(花石峡海拔4380 m)与平原组(北京海拔43 m)健康人外周血标本172份.其中高原组95名(男性47名,女性48名),平原组77名(男性39名,女性38名).两组年龄分布基本相同.实验采用Southern杂交方法检测其端粒限制性片段长度(terminal restriction fragment,TRF),邻苯三酚氧化法测定超氧化物歧化酶(SOD),硫代巴比妥(TBA)比色法测定丙二醛(MDA)并做统计学分析.结果 高原组与平原组健康人平均TRF检测结果,高原组男性TRF值为10.45±1.35,女性为10.50±1.45;平原组男性TRF值为11.29±1.10,女性为11.31±1.13;高原组与平原组男性与女性TRF.值均与年龄呈负相关性;对高原组与平原组分别进行男性与女性4个不同年龄段间方差分析,4个年龄段均数间进行比较发现无论男性或女性,高原组与平原组25及55岁组比较,差异有统计学意义.25～44岁和45～65岁高原组和平原组相同年龄段组SOD,MDA测定值相比较,差异有统计学意义.结论 高原组人FRF均随年龄增长而逐渐缩短,TRF与年龄间存在负相关关系;高原组与平原组不同性别TRF不同,高原组TRF水平低于平原组;随着年龄的增长高原组TRF缩短更明显.     

父代n-3多不饱和脂肪酸对子代小鼠端粒长度的影响

目的 探讨父代备孕期n-3多不饱和脂肪酸(n-3 PUFAs)对子代端粒长度(TL)的影响。方法 将3～4周龄C57BL/6J雄性小鼠(父代)随机分为3组(10只/组),分别给予n-3 PUFAs缺乏(n-3 D)、n-3 PUFAs正常含量(n-3 N)和n-3 PUFAs高含量(n-3 H)饲料饲喂12周，然后与12周龄正常体重的同品系雌性小鼠交配繁育子代小鼠。对成年期子代小鼠进行外周血和组织TL以及端粒酶和端粒结合蛋白基因mRNA表达检测。结果 与n-3 N饲料相比，父代n-3 D饲料喂养使得子代雌和雄性小鼠的外周血、肝脏、脂肪组织和/或脑组织中的TL显著缩短，伴随雄性肝脏端粒酶组分TERC以及结合蛋白TRF2和POT1a的mRNA表达下调；同时显著缩短了子代睾丸TL并下调了端粒酶(TERT)和结合蛋白(TRF1、TRF2、POT1a)的mRNA表达。父代n-3 H饲料喂养虽然未改变子代的TL和肝脏端粒酶及结合蛋白表达，但却显著逆转了n-3 D饲料的不良影响。另外，相对于n-3 N饲料，父代n-3 D和n-3 H饲料喂养均未改变自身睾丸TL,但n-3 H饲料喂养时睾丸TL以及端粒...     

人外周血基因组DNA端粒长度与肺癌关系

目的 观察外周血基因组DNA端粒长度与肺癌危险性的关系.方法 用荧光定量PCR法检测145例肺癌患者、145名正常对照和145名焦炉工人外周血基因组DNA相对端粒长度.结果 肺癌组端粒长度明显短于对照组(P=0.028),职业暴露组端粒长度明显短于肺癌组(P=0.005)和对照组(P<0.001);按对照组端粒长度分4组,随着端粒的缩短,肺癌的危险性增加(Ptrend<0.001);按对照组端粒长度中位数把样本分为2组发现,与长端粒组比较,端粒变短明显增加肺癌的危险性(调整OR=2.337,95%CI为1.413～3.866);对照组中,随着年龄增加,端粒缩短(P<0.001).结论 端粒缩短可增加肺癌的危险性,可能是肺癌发展早期过程中的一项重要的生物标志.     

外周血白细胞端粒长度与轻度认知障碍老年人发生风险关联的病例对照研究

目的  探讨轻度认知障碍(mild cognitive impairment, MCI)老年人外周血白细胞端粒长度(leukocyte telomere length, LTL)与MCI发生风险之间的关联。 方法  于2017年10月-2017年12月在天津市南开区王顶堤街道的5个社区纳入MCI和健康对照老年受试者进行病例对照设计, 实施问卷调查和静脉血样采集, 用实时荧光定量多聚核苷酸链式反应(real-time quantitative polymerase chain reaction, qPCR)进行LTL的测量。采用多元Logistic回归分析模型分析LTL不同水平与MCI发生风险之间的关联。 结果  两组受试对象都为183例。MCI组LTL水平(1.44±0.23)低于对照组(1.66±0.23), 两组差异具有统计学意义(Z=-8.94, P < 0.001)。调整年龄、性别、教育程度、吸烟、饮酒、糖尿病、高血压、心脏病后, 较低水平LTL与MCI发生风险存在统计学意义关联(均有P < 0.05);与LTL第一水平组相比, 其二、三、四水平组MCI发生风险的比值比(odds ratio, OR)及95%置信区间(95% confidence interval, 95% CI)分别为0.262(0.130~0.531)、0.088(0.043~0.180)、0.083(0.040~0.169)。 结论  外周血白细胞短端粒可能是MCI发生的独立危险因素, 并且随着LTL缩短, MCI发生风险增加。     

不同营养状况儿童白细胞端粒长度与血压的相关性分析

分析儿童端粒长度与血压水平以及血压偏高检出率之间的关联性,为有效预防儿童高血压提供参考.方法 在2012年卫生行业科研专项基线数据库中,按照体质量指数(BMI)筛选湖南、天津、辽宁、上海4省市7~12岁儿童253名,按照BMI水平分为正常体重(81名)、超重和轻中度肥胖(85名)、重度肥胖(87名)3组,采用实时荧光定量PCR方法测定白细胞端粒长度,并计算对数转换的端粒长度.采用Pearson相关分析端粒长度与血压水平之间的关联性.结果 采用美国国家高血压教育项目(NHBPEP)标准和中国高血压联盟(CHL)标准,253名7~12岁儿童的血压偏高检出率分别为15.81%和24.90%,男生分别为17.36%和28.93%,女生分别为14.39%和21.21%,男生均高于女生,差异均无统计学意义(P值均>0.05).基于NHBPEP标准,血压偏高组儿童的端粒检测长度(TLT)和对数转换长度(Log-TLT)分别为1.07和0.02,与正常血压组儿童长度(分别为1.09和0.03)差异均无统计学意义(P值均>0.05);基于CHL标准,血压偏高组儿童的端粒长度TLT和Log-TLT分别为1.09和0.03,与正常血压组儿童长度(1.08和0.03)差异均无统计学意义(P值均>0.05).男、女生呈现相同趋势,差异无统计学意义(P>0.05).在BMI正常、超重和轻中度肥胖、重度肥胖3组学生中基本呈现相同趋势.结论 儿童时期端粒长度与血压水平和血压偏高检出无明显的关联性,还需要进一步在成人人群中进行验证.     

行为生活方式对端粒长度影响的研究进展

端粒是位于染色体末端维持基因稳定的DNA-蛋白质复合体。正常体细胞端粒长度由于“末端复制问题”会随着年龄的增加而缩短。端粒长度缩短的速度受到遗传因素和非遗传因素的影响,由于非遗传因素（如行为生活方式等）可以通过人为干预进行改善,故探明非遗传因素与端粒长度的关联性具有十分重要的意义。相关性研究分析了睡眠、体力活动、吸烟、压力、膳食等行为生活方式与端粒长度的关系,本文对以上研究结果进行比较归纳,并进一步探讨不同行为生活方式对端粒长度的影响,为延缓端粒损伤、促进健康衰老提供理论依据。     

镉对小鼠肾脏细胞凋亡的影响

目的 研究镉对小鼠肾脏细胞凋亡的影响。方法 将小鼠分成5组,分别注射0．9％生理盐水,80、160、240或320mg／kg的CdCl2溶液,连续6周,于染毒4周和6周后每组处死一半小鼠,测定肾脏系数,用流式细胞术检测细胞凋亡,用免疫组化法测Bcl—2。结果 染镉组小鼠肾脏系数较对照组显著增高,而且细胞凋亡率较对照组明显增高,Bcl—2蛋白表达明显下降。结论 镉可诱导小鼠肾脏细胞凋亡。     

亚低温对新生大鼠缺血脑凋亡细胞数和bcl—2表达的影响

目的 明确缺氧缺血性脑损害（HIBD）后亚低温干预对脑组织bcl-2和凋亡细胞数的影响其及相关性。方法 建立新生大鼠HIBD模型,31℃亚低温干预,采用原位末端标记技术观察脑组织凋亡细胞数,免疫组化法观察脑bcl-2表达水平,作统计分析。结果 新生HIBD大鼠8日龄时凋亡细胞大量出现（P＜0．01）,并达高峰,亚低温干预使8日龄凋亡细胞数减少（P＜0．01）,高峰后移;新生HIBD大鼠8日龄开始有bcl-2大量表达（P＜0．01）,8－10日龄其水平最高,亚低温干预使bcl-2表达水平下降（P＜0．01）;8日龄时bcl-2水平与8日龄脑海马及皮质凋亡细胞数呈等级正相关,相关系数分别为0．88及0．71（均为P＜0．05）;10日龄bcl-2水平与10日龄海马凋亡细胞数等级正相关,相关系数0．75（P＜0．05）,与皮质凋亡细胞数无相关意义。结论 新生大鼠HIBD后早期发生凋亡过程,bcl-2水平与凋亡数一致;亚低温干预使凋亡过程延缓,高峰时间的调亡细胞数及bcl-2水平降低,从而保护脑组织。     

电阻抗测量技术对兔脑急性缺血监测初步实验研究

目的：研究家兔脑急性缺血时脑阻抗的定性变化及频率特性。方法：采用第四军医大学医学电子工程教研室研制的阻抗监护系统（激励电流1 mA,激励频率：100、200、400、600、800 Hz和1、2、4、6、8、10、20、40、60、80、100、180 kHz,采用四电极法）,用双侧颈总动脉阻断法建立兔脑缺血模型后对9只家兔进行脑阻抗监测。结果：兔脑缺血后,脑阻抗实部、虚部绝对值均明显升高。对兔脑阻抗缺血前后数据进行配对t检验,具有显著性差异（P〈0.001）。缺血150 s时,在8 Hz频率点,阻抗变化率最大,实部1.36%,模1.38%;900 s时,在6 kHz频率点,阻抗变化率最大,实部15.5%,模15.4%。结论：采用电阻抗技术对脑缺血进行监测是可行的。采用不同的测量频率会得到不同的脑部电阻抗变化量。阻抗最大变化率频率点随时间从8 kHz向6 kHz转移。脑急性缺血后阻抗实部、虚部和模变化率的频谱特性随着时间变化而变化,以往单一频率的监测并不能全面反映脑急性缺血后的阻抗变化信息。     

Disruption of Telomere–Telomere Interactions Associated with DNA Damage in Human Spermatozoa

Telomeres play a fundamental role in the organization of the sperm nucleus resulting in the looped chromosome configuration and non-random positioning of chromosomes. Telomeres localize in the nuclear periphery and interact dynamically by forming dimers and tetramers. The purpose of this study was to evaluate the relationship of telomere interactions to DNA damage, a factor known to adversely influence male fertility.

Telomeres were localized by fluorescence in situ hybridization (FISH) using human chromosome pan-telomeric probe in ten samples with low and ten samples with high sperm DNA damage. The samples with a low DNA fragmentation index (DFI) had a mean number of telomere signals of 21.7±1.9 compared to a mean of 26.5±3.4 signals in the samples with a high DFI (p<.005). The percentage of cells with a typical telomere distribution of ≤23 telomere-telomere dimers was observed in 70.8%±15.6 samples with a low DFI compared to 44.2%±22.4 in samples with a high DFI (p<.05).

These results suggest that sperm DNA damage is associated with disruption of the normal telomere–telomere interactions leading to possible loss of the looped chromosome configuration. Improperly packed and organized sperm chromatin might have a high probability of disrupting the extremely structured sequence of sperm chromosome deposition, activation, and processing by the oocyte at the time of fertilization. These results might provide additional information on the nature of sperm DNA damage and the role of such damage on fertilization and development of the zygote.     

The Association Between Global DNA Methylation and Telomere Length in a Longitudinal Study of Boilermakers

The objectives of this study were to determine if global DNA methylation, as reflected in LINE‐1 and Alu elements, is associated with telomere length and whether it modifies the rate of telomeric change. A repeated‐measures longitudinal study was performed with a panel of 87 boilermaker subjects. The follow‐up period was 29 months. LINE‐1 and Alu methylation was determined using pyrosequencing. Leukocyte relative telomere length was assessed via real‐time qPCR. Linear‐mixed models were used to estimate the association between DNA methylation and telomere length. A structural equation model (SEM) was used to explore the hypothesized relationship between DNA methylation, proxies of particulate matter exposure, and telomere length at baseline. There appeared to be a positive association between both LINE‐1 and Alu methylation levels, and telomere length. For every incremental increase in LINE‐1 methylation, there was a statistically significant 1.0 × 10^?1 (95% CI: 4.6 × 10^?2, 1.5 × 10^?1, P < 0.01) unit increase in relative telomere length, controlling for age at baseline, current and past smoking status, work history, BMI (log kg/m²) and leukocyte differentials. Furthermore, for every incremental increase in Alu methylation, there was a statistically significant 6.2 × 10^?2 (95% CI: 1.0 × 10^?2, 1.1 × 10^?1, P = 0.02) unit increase in relative telomere length. The interaction between LINE‐1 methylation and follow‐up time was statistically significant with an estimate ?9.8 × 10^?3 (95% CI: ?1.8 × 10^?2, ?1.9 × 10^?3, P = 0.02); suggesting that the rate of telomeric change was modified by the degree of LINE‐1 methylation. No statistically significant association was found between the cumulative PM exposure construct, with global DNA methylation and telomere length at baseline.     

半胱胺酸蛋白酶抑制剂防治缺血性脑损伤研究

半胱胺酸蛋白酶抑制剂能阻断凋亡所需的特异蛋白酶 ,与其它神经保护剂相比具有较宽的治疗窗。该文从半胱胺酸蛋白酶抑制剂种类 ,作用机制 ,治疗窗等多个方面来阐述半胱胺酸蛋白酶抑制剂 ,探讨半胱胺酸蛋白酶抑制剂在新生儿缺氧缺血性脑损伤 (HIBD)中的治疗价值。     

SD大鼠急性脑梗死静脉溶栓后缺血半暗带VEGFmRNA的早期表达

目的研究VEGFmRAN在大鼠急性脑梗死静脉溶栓后缺血半暗带区的早期表达。方法建立大鼠自体血栓脑梗死模型,选择栓塞后不同时间点（3、6、12、24h）,采用逆转录一聚合酶链反应（RT—PCR）半定量测定缺血半暗带区VEGFmRNA的表达,比较rtPA静脉溶栓组和对照组的差异。结果在各时间点,溶栓组VEGFmRNA表达的平均值均高于对照组,但只在12h时间点达到统计学差异。结论大鼠自体血栓脑梗死后静脉溶栓治疗有促进缺血侧脑组织VEGFmRNA表达的趋势。     

Association of Average Telomere Length with Body-Mass Index and Vitamin D Status in Juvenile Population with Type 1 Diabetes

Background

Type 1 diabetes (T1D) is an autoimmune chronic disease where hyperglycemia, increased risk of oxidative stress, advanced glycation end-products and other genetic and environmental factors lead to T1D complications. Shorter telomeres are associated with hyperglycemic levels and lower serum vitamin D levels.

Methods

Average telomere length (ATL) in whole blood DNA samples was assessed with qPCR method in 53 Slovenian T1D children/adolescents (median age 8.7 years, 1:1.3 male/female ratio). Body mass index standard deviation score (BMI-SDS), glycated haemoglobin and serum level of vitamin D metabolite (25-(OH)-D3) and the age at the onset of T1D were collected from the available medical documentation.

Results

Results indicate shorter ATL in subjects with higher BMI-SDS when compared to those with longer ATL (0.455 ± 0.438, −0.63 ± 0.295; p=0.049). Subjects with higher BMI-SDS had lower serum vitamin D levels when compared to those with lower BMI-SDS (40.66 ± 3.07 vs. 52.86 ± 4.85 nmol/L; p=0.045). Vitamin D serum levels did not significantly differ between subjects with longer/shorter ATL.

Conclusion

T1D children/adolescents with shorter ATL tend to have higher BMI-SDS. Lower serum vitamin D levels were associated with higher BMI-SDS, while associations between vitamin D serum levels, age at the onset of T1D, glycated haemoglobin and ATL were not observed. Additional studies with more participants are required to clarify the role of the telomere dynamics in T1D aetiology and development of complications.     

n-3 Fatty Acid Supplementation and Leukocyte Telomere Length in Patients with Chronic Kidney Disease

DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F₂-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015). Post-intervention plasma F₂-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.     

A Comprehensive,Multidisciplinary, Personalized,Lifestyle Intervention Program Is Associated with Increased Leukocyte Telomere Length in Children and Adolescents with Overweight and Obesity

Leucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life.