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不同海拔高度对大鼠外周血白细胞端粒长度的影响及其机制研究

王亚平, 杨应忠, 马兰, 赵艳霞, 格日力^*

青海大学医学院高原医学研究中心，西宁 810001

摘要

本文旨在探讨不同海拔高度对大鼠外周血白细胞端粒长度的影响及其可能的机制。60只雄性Wistar大鼠随机分为低海拔对照组(南京，海拔10 m)、中度海拔组(西宁，海拔2 260 m)和特高海拔组(低压氧舱，模拟海拔5 000 m)。将中度海拔组和特高海拔组大鼠分别由南京快速运至西宁地区和青海大学低压氧舱室，30 d后抽取大鼠外周血标本。用荧光实时定量PCR检测大鼠外周血白细胞端粒长度，用全自动血细胞分析仪检测静脉血血红蛋白(hemoglobin, Hb)含量，ELISA法检测血浆端粒酶逆转录酶(telomerase reverse transcriptase, TERT)及低氧诱导因子1α (hypoxia-inducible factor-1α, HIF-1α)水平，WST-1法测定超氧化物歧化酶(superoxide dismutase, SOD)活力，TBA比色法测定丙二醛(malondialdehyde, MDA)含量。结果显示，中度海拔组大鼠外周血白细胞端粒长度长于低海拔对照组与特高海拔组，血浆TERT水平的变化与端粒长度一致；中度海拔组与特高海拔组大鼠血浆HIF-1α水平高于低海拔组；相对低海拔对照组和中度海拔组，特高海拔组大鼠血浆SOD活力下降，MDA水平增高。上述结果提示，中度海拔高度下大鼠外周血白细胞端粒长度延长，而极高海拔高度下此端粒延长作用消失，其中HIF-1α、TERT水平变化及氧化应激损伤是引起其端粒长度变化的主要机制；中度海拔地区居住可能有益于延长哺乳类动物的寿命。

关键词： 端粒; 不同海拔高度; 端粒酶逆转录酶; 低氧诱导因子1α; 超氧化物歧化酶; 丙二醛

分类号：R363.16

[Effect of different altitudes on telomere length of rat peripheral blood leukocyte and possible mechanism.] [Article in Chinese]

WANG Ya-Ping, YANG Ying-Zhong, MA Lan, ZHAO Yan-Xia, GE Ri-Li^*

Research Center for High Altitude Medical Sciences, Medical College of Qinghai University, Xining 810001, China

Abstract

The present study was aimed to investigate the effect of different altitudes on telomere length of rat peripheral blood leukocyte and possible mechanism. Sixty male rats were randomly divided into three groups, lower altitude control group (10 m), moderate altitude group (2 260 m) and very high altitude group (simulated 5 000 m). The moderate altitude group and very high altitude group rats were transported to Xining and hypobaric chamber in Qinghai University, respectively. The peripheral blood specimens were extracted 30 d after the transportation. By means of real-time PCR, automatic blood cell analyzer, ELISA, TBA and WST-1 methods, the telomere lengths of blood leukocyte, the hemoglobin (Hb) contents, the plasma levels of telomerase reverse transcriptase (TERT) and hypoxia-inducible factor 1α (HIF-1α), the plasma content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured, respectively. The results showed that the telomere lengths of peripheral blood leukocyte in moderate altitude group were longer than those in control group and very high altitude group. The changes of TERT were compatible with the telomere length of peripheral blood leukocyte under different altitudes. The levels of HIF-1α in moderate altitude group and very high altitude group were higher than that of control group. The very high altitude group showed decreased SOD activities and increased level of MDA, compared with the other two groups. These results suggest that the telomere lengths of rat peripheral blood leukocyte in moderate altitude are elongated, and that the telomere-elongating effect is lost under very high altitude. The changes of HIF-1α, TERT and oxidative stress damage are the main mechanisms of telomere length changes. Moderate altitude living might be beneficial to increasing the life span in mammals.

Key words: Telomere; different altitudes; telomerase reverse transcriptase; hypoxia-inducible factor 1α; superoxide dismutase; malondialdehyde

收稿日期：2013-04-03　　录用日期：2013-06-20

通讯作者：格日力　　E-mail: geriligao@hotmail.com

引用本文：

王亚平, 杨应忠, 马兰, 赵艳霞, 格日力. 不同海拔高度对大鼠外周血白细胞端粒长度的影响及其机制研究[J]. 生理学报 2013; 65 (5): 540-546.

WANG Ya-Ping, YANG Ying-Zhong, MA Lan, ZHAO Yan-Xia, GE Ri-Li. [Effect of different altitudes on telomere length of rat peripheral blood leukocyte and possible mechanism.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (5): 540-546 (in Chinese with English abstract).