Lv Sa, Wang Jiang-hua, Liu Feng, Gao Yan, Fei Ran, Du Shao-cai, Wei Lai
Peking University People's Hospital, Peking University Hepatology Institute, Beijing 100044, PR China.
BMC Gastroenterol. 2008 May 28;8:17. doi: 10.1186/1471-230X-8-17.
Our previous proteomic study showed that the senescence marker protein (SMP30) is selectively present in the plasma of a murine model of acute liver failure (ALF). The aim of this study was to validate this SMP30 expression in the plasma and liver tissues of mice and humans with ALF.
After the proteomic analysis of plasma from a murine model of D-galactosamine/lipopolysaccharide (GalN/LPS)-induced ALF by two-dimensional electrophoresis (2-DE) and mass spectrometry, the expression levels of SMP30 in the plasma and liver tissues were validated by western blot and RT-PCR analyses. These results were then confirmed in plasma samples from humans.
These data validate the results of 2-DE, and western blot showed that SMP30 protein levels were only elevated in the plasma of ALF mice. Further analysis revealed that GalN/LPS induced the downregulation of SMP30 protein levels in liver tissues (by approximately 25% and 16% in the GalN/LPS-treated mice and in the treated mice that survived, respectively; P < 0.01). Hepatic SMP30 mRNA levels decreased by about 90% only in the mice that survived the GalN/LPS treatment. Importantly, plasma obtained from patients with ALF also contained higher levels of SMP30, about (3.65 +/- 0.34) times those observed in healthy volunteers.
This study shows that SMP30 is not only a potential biomarker for the diagnosis and even prognosis of ALF. It also plays a very important role in a self-protective mechanism in survival and participates in the pathophysiological processes of ALF.
我们之前的蛋白质组学研究表明，衰老标记蛋白（SMP30）选择性地存在于急性肝衰竭（ALF）小鼠模型的血浆中。本研究的目的是验证ALF小鼠和人类血浆及肝组织中这种SMP30的表达情况。
通过二维电泳（2-DE）和质谱对D-半乳糖胺/脂多糖（GalN/LPS）诱导的ALF小鼠模型的血浆进行蛋白质组学分析后，通过蛋白质印迹和RT-PCR分析验证血浆和肝组织中SMP30的表达水平。然后在人类血浆样本中证实这些结果。
这些数据验证了2-DE的结果，蛋白质印迹显示SMP30蛋白水平仅在ALF小鼠的血浆中升高。进一步分析表明，GalN/LPS诱导肝组织中SMP30蛋白水平下调（在GalN/LPS处理的小鼠和存活的处理小鼠中分别下调约25%和16%；P<0.01）。仅在GalN/LPS处理后存活的小鼠中，肝脏SMP30 mRNA水平下降了约90%。重要的是，从ALF患者获得的血浆中也含有较高水平的SMP30，约为健康志愿者中观察到水平的（3.65±0.34）倍。
本研究表明，SMP30不仅是ALF诊断甚至预后的潜在生物标志物。它在生存的自我保护机制中也起着非常重要的作用，并参与ALF的病理生理过程。
