王亚平，格日力

(1.青海省人民医院消化科；2.青海大学医学院高原医学研究中心)



不同海拔及时间下大鼠白细胞TERT及HIF-1α mRNA的表达及其对机体细胞寿命的影响和可能机制※

王亚平1，2，格日力2

(1.青海省人民医院消化科；2.青海大学医学院高原医学研究中心)

摘要目的研究不同海拔及时间下大鼠白细胞TERT及HIF-1α mRNA的表达规律，并探讨其对机体细胞寿命的影响及其可能机制。方法110只大鼠随机分为低海拔对照组、中度海拔组及特高海拔组，后两组根据时间不同分为1、3、7、15、30天组，每组各10只。采用real-time PCR法检测大鼠白细胞端粒酶逆转录酶(TERT)及低氧诱导因子1α(HIF-1α)mRNA表达水平，并行相关意义分析。结果中度海拔组大鼠白细胞TERT mRNA水平明显高于低海拔与特高海拔组(P<0.05)，各组TERT mRNA水平变化与时间相关；HIF-1α mRNA在中度海拔与特高海拔组表达均升高，中度海拔组又高于特高海拔组(P<0.05)，其变化趋势与TERT水平的变化基本一致。结论轻度低氧可通过HIF-1α上调TERT的表达，从而使白细胞端粒酶活性升高、端粒长度延长、机体细胞寿命增加。

关键词海拔时间端粒酶逆转录酶低氧诱导因子1α

EXPRESSIONS OF TERT AND HIF-1α mRNA IN RAT

LEUKOCYTES UNDER DIFFERENT ALTITUDES AND

DIFFERENT PERIODS OF TIME AS WELL AS THE INFLUENCE

AND POSSIBLE MECHANISM ON THE LIFE SPAN OF CELLS

Wang Yaping1，2，Ge Rili2

(1.Digestive Department of Qinghai Provincial People′s Hospital，Xining，810007；

2.Research Center for High Altitude Medical Sciences，Medical College of Qinghai University，Xining，810001)

Abstract ObjectiveTo investigates the changes of TERT and HIF-1α mRNA in rat leukocytes under different altitudes and different periods of time，discusses the influence and possible mechanism on the life span of body cells.Methods 110 rats were randomly divided into three groups，low altitude group，moderate altitude group and very high altitude group.The later two groups were further divided into 1，3，7，15 and 30 days groups，with 10 rats in each group.TERT and HIF-1α mRNA levels of leukocytes were measured using real-time PCR，and analyzed the related significance.Results The TERT mRNA expression of leukocytes in moderate altitude group was significantly higher than control group and very high altitude group(P<0.05)，and the changes of TERT mRNA expression are associated with time.The HIF-1α mRNA expression in moderate altitude group and very high altitude group were higher than that of control group(P<0.05)，however，the HIF-1α expression was much higher in the moderate altitude group than in the very high altitude group.HIF-1α mRNA expression changed in a similar manner as the TERT mRNA.Conclusions The TERT expression was up-regulated following the induction of HIF-1α during exposure to mild hypoxia，it makes the increasing of activity for leukocytes telomerase and the elongatin of telomere length，the life span on cells was extended.

KeywordsAltitudesTimeTelomerase reverse transcriptaseHypoxia-inducible factor 1α

高原环境有诸多不利因素作用于人体，其中低氧是影响和损伤机体的关键。目前关于低氧对细胞端粒酶逆转录酶(telomerase reverse transcriptase，TERT)、端粒酶(telomerase)及端粒(telomere)影响的研究报道逐渐增多，但其主要集中在对离体干细胞及肿瘤细胞的短期研究，缺乏不同低氧水平及时间下在体体细胞的系统观察比较[1-3]。因此本研究从整体水平上观察不同海拔及不同时间下大鼠白细胞TERT及低氧诱导因子1α(hypoxia-inducible factor-1α，HIF-1α)mRNA的表达水平及变化规律，并探讨其对机体细胞寿命的影响及其可能机制。

1材料与方法

1.1动物处理

110只健康雄性Wistar 大鼠[(180±20)g，购自中国药科大学实验动物中心，动物合格证号：SCXK(苏)2009-009]随机分为 3 组：低海拔对照组 10只(LA，南京，10m)，中度海拔组50只(MA，西宁，2260m)，特高海拔组 50只(VHA，低压氧舱模拟，5000m)，后两组根据暴露时间不同分为1、3、7、15、30天组，每组各10只。……