Stan Ana D, Ghose Subroto, Gao Xue-Min, Roberts Rosalinda C, Lewis-Amezcua Kelly, Hatanpaa Kimmo J, Tamminga Carol A
University of Texas Southwestern Medical Center at Dallas, Department of Psychiatry, 5323 Harry Hines Blvd., NE5.110F, Dallas, TX 75390-9127, USA.
Brain Res. 2006 Dec 6;1123(1):1-11. doi: 10.1016/j.brainres.2006.09.025. Epub 2006 Oct 12.
Postmortem human brain tissue is used for the study of many different brain diseases. A key factor in conducting postmortem research is the quality of the tissue. Unlike animal tissue, whose condition at death can be controlled and influenced, human tissue can only be collected naturalistically. This introduces potential confounds, based both on pre- and postmortem conditions, that may influence the quality of tissue and its ability to yield accurate results. The traditionally recognized confounds that reduce tissue quality are agonal factors (e.g., coma, hypoxia, hyperpyrexia at the time of death), and long postmortem interval (PMI). We measured tissue quality parameters in over 100 postmortem cases collected from different sources and correlated them with RNA quality (as indicated by the RNA Integrity Number (RIN)) and with protein quality (as measured by the level of representative proteins). Our results show that the most sensible indicator of tissue quality is RIN and that there is a good correlation between RIN and the pH. No correlation developed between protein levels and the aforementioned factors. Moreover, even when RNA was degraded, the protein levels remained stable. However, these correlations did not prove true under all circumstances (e.g., thawed tissue, surgical tissue), that yielded unexpected quality indicators. These data also suggest that cases whose source was a Medical Examiner's office represent high tissue quality.
尸检获得的人脑组织被用于多种不同脑部疾病的研究。开展尸检研究的一个关键因素是组织的质量。与动物组织不同,动物死亡时的状况可以得到控制和影响,而人体组织只能自然采集。这就引入了基于生前和死后状况的潜在混杂因素,这些因素可能会影响组织质量及其产生准确结果的能力。传统上公认的会降低组织质量的混杂因素包括濒死因素(例如,死亡时的昏迷、缺氧、高热)以及较长的死后间隔时间(PMI)。我们在从不同来源收集的100多例尸检病例中测量了组织质量参数,并将它们与RNA质量(由RNA完整性数值(RIN)表示)以及蛋白质质量(通过代表性蛋白质水平测量)进行关联。我们的结果表明,组织质量最合理的指标是RIN,并且RIN与pH值之间存在良好的相关性。蛋白质水平与上述因素之间未发现相关性。此外,即使RNA降解,蛋白质水平仍保持稳定。然而,在所有情况下(例如,解冻组织、手术组织)这些相关性并不成立,这些情况会产生意想不到的质量指标。这些数据还表明,来自法医办公室的病例代表着高质量的组织。