Ip S P, Wong T P, Tsai S J, Leung P S
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
J Mol Endocrinol. 2003 Dec;31(3):563-71. doi: 10.1677/jme.0.0310563.
Previous studies have shown that the expression of the major components from a local pancreatic renin-angiotensin system (RAS) was upregulated after chronic exposure to oxygen deprivation (10% oxygen). In the present study, the reversibility of expression for the pancreatic RAS affected by chronic hypoxia was investigated in the pancreas. Rats were first subject to hypoxia for one Month and they were then returned to normoxic conditions for a varying period of time (1, 2, 3 and 4 weeks). The degree of recovery in the expression of RAS components was analyzed with standard curve-quantitative competitive-reverse transcription-polymerase chain reaction (SC-QC-RT-PCR), Western blot analysis and a specific assay for angiotensin-converting enzyme (ACE) activity. Results from SC-QC-RT-PCR showed that the upregulated expression of angiotensin II type 1 (AT(1)) receptor mRNA following chronic hypoxia could be completely restored to the control level after the rats were returned to the normoxic condition for 3 weeks. The reversibility of mRNA expression for angiotensin II type 2 (AT(2)) receptor and angiotensinogen was observed after the return to normoxic conditions for 2 and 3 weeks respectively when compared with that of their respective controls. Results from Western blot analysis further confirmed that the expression of AT(1) receptor protein was also reversible after return to normoxic conditions for 4 weeks. In addition, the activation of ACE activity returned to its normal level in a time-dependent manner. These data indicate that the upregulation of a local pancreatic RAS affected by chronic hypoxia could be recoverable. The significance of its reversibility and adaptability following chronic hypoxia may be of physiological relevance to the pancreas.
先前的研究表明,长期暴露于低氧环境(10%氧气)后,局部胰腺肾素-血管紧张素系统(RAS)的主要成分表达上调。在本研究中,在胰腺中研究了受慢性缺氧影响的胰腺RAS表达的可逆性。大鼠首先经历1个月的缺氧,然后将它们恢复到常氧条件下不同的时间段(1、2、3和4周)。使用标准曲线-定量竞争-逆转录-聚合酶链反应(SC-QC-RT-PCR)、蛋白质免疫印迹分析和血管紧张素转换酶(ACE)活性特异性测定法分析RAS成分表达的恢复程度。SC-QC-RT-PCR结果显示,慢性缺氧后血管紧张素II 1型(AT(1))受体mRNA的上调表达在大鼠恢复到常氧条件3周后可完全恢复到对照水平。与各自对照相比,血管紧张素II 2型(AT(2))受体和血管紧张素原的mRNA表达分别在恢复到常氧条件2周和3周后观察到可逆性。蛋白质免疫印迹分析结果进一步证实,恢复到常氧条件4周后,AT(1)受体蛋白的表达也是可逆的。此外,ACE活性的激活以时间依赖性方式恢复到正常水平。这些数据表明,受慢性缺氧影响的局部胰腺RAS的上调可能是可恢复的。其在慢性缺氧后的可逆性和适应性的意义可能与胰腺的生理相关性有关。