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端粒缩短是否先于自发性高血压小鼠高血压的发作?

Does Telomere Shortening Precede the Onset of Hypertension in Spontaneously Hypertensive Mice?

作者信息

Chiu Christine L, Hearn Nerissa L, Paine Devin, Steiner Nicole, Lind Joanne M

机构信息

Western Sydney University,School of Medicine, Sydney, New South Wales,Australia.

出版信息

Twin Res Hum Genet. 2016 Oct;19(5):422-9. doi: 10.1017/thg.2016.63. Epub 2016 Aug 12.

Abstract

Telomere length is widely considered as a marker of biological aging. Clinical studies have reported associations between reduced telomere length and hypertension. The aim of this study was to compare telomere length in hypertensive and normotensive mice at pre-disease and established disease time points to determine whether telomere length differs between the strains before and after the onset of disease. Genomic DNA was extracted from kidney and heart tissues of 4-, 12-, and 20-week-old male hypertensive (BPH/2J) and normotensive (BPN/3J) mice. Relative telomere length (T/S) was measured using quantitative PCR. Age was inversely correlated with telomere length in both strains. In 4-week-old pre-hypertensive animals, no difference in T/S was observed between BPH/2J and BPN/3J animals in kidney or heart tissue (kidney p = 0.14, heart p = 0.06). Once the animals had established disease, at 12 and 20 weeks, BPH/2J mice had significantly shorter telomeres when compared to their age-matched controls in both kidney (12 weeks p < 0.001 and 20 weeks p = 0.004) and heart tissues (12 weeks p < 0.001 and 20 weeks p < 0.001). This is the first study to show that differences in telomere lengths between BPH/2J and BPN/3J mice occur after the development of hypertension and do not cause hypertension in the BPH/2J mice.

摘要

端粒长度被广泛认为是生物衰老的一个标志。临床研究报告了端粒长度缩短与高血压之间的关联。本研究的目的是比较高血压小鼠和血压正常小鼠在疾病前期和疾病确立时间点的端粒长度,以确定在疾病发作前后这两个品系之间的端粒长度是否存在差异。从4周龄、12周龄和20周龄的雄性高血压(BPH/2J)和血压正常(BPN/3J)小鼠的肾脏和心脏组织中提取基因组DNA。使用定量PCR测量相对端粒长度(T/S)。在两个品系中,年龄与端粒长度呈负相关。在4周龄的高血压前期动物中,BPH/2J和BPN/3J动物在肾脏或心脏组织中的T/S没有差异(肾脏p = 0.14,心脏p = 0.06)。一旦动物确立了疾病,在12周和20周时,与年龄匹配的对照组相比,BPH/2J小鼠在肾脏(12周p < 0.001,20周p = 0.004)和心脏组织(12周p < 0.001,20周p < 0.001)中的端粒明显更短。这是第一项表明BPH/2J和BPN/3J小鼠之间的端粒长度差异在高血压发生后出现,且不会在BPH/2J小鼠中导致高血压的研究。

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