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常氧和缺血大鼠肠道中Survivin的表达模式

Survivin expression pattern in the intestine of normoxic and ischemic rats.

作者信息

Scheer Alexandra, Knauer Shirley K, Verhaegh Rabea

机构信息

Institute of Physiological Chemistry, University Hospital Essen, Hufelandstraße 55, D-45147, Essen, Germany.

Institute for Molecular Biology, Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.

出版信息

BMC Gastroenterol. 2017 Jun 14;17(1):76. doi: 10.1186/s12876-017-0625-6.

Abstract

BACKGROUND

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, regulates mitosis and chromosome segregation. The expression of survivin proceeds during embryonic development and in addition has already been demonstrated in cancer cells. However, there is also evidence of survivin expression in differentiated tissues, including the gastro-intestinal tract of adult rats. A study with human colon specimens exhibited survivin in most basal crypt epithelial cells of normal mucosa. There is rather limited information on survivin expression in the small intestine. In order to paint a more detailed and thus complete picture of survivin expression patterns in the gastrointestinal tract, we used an immunohistochemical approach in normal adult rat small intestinal and ascending colonic tissue. Moreover, to get deeper insights in the regulation of survivin expression after tissue damage, we also studied its expression in mesenteric ischemia-reperfusion (I/R) injury.

METHODS

Mesenteric ischemia-reperfusion injury was induced in male Wistar rats (six animals/group) by occlusion of the superior mesenteric artery for 90 min and subsequent reperfusion for 120 min. Paraffin sections of untreated or ischemically treated tissue were assessed immunohistochemically by survivin and Ki-67 staining.

RESULTS

Survivin could be detected in the small intestine and ascending colon of the normoxia group. It was expressed mainly in the epithelial cells of the crypts and only marginally in the villi. The individual small intestinal segments studied revealed comparable staining intensities. Likewise, expression of survivin was detected in the ischemically damaged small intestine and ascending colon. The expression pattern corresponded to the normoxic animals, as far as verifiable due to the existing tissue damage. Comparison of the expression pattern of Ki-67, a protein that acts as a cellular marker for proliferation, and survivin demonstrated a coincidental localization of the two proteins in the small intestinal and ascending colonic tissue.

CONCLUSIONS

Survivin was expressed strongly in epithelial cells of small intestinal as well as ascending colonic tissue. Its expression was located in cells with a high proliferation rate and regenerative capacity. This further supports the decisive role of survivin in cell division. Surprisingly, the ischemically damaged small intestinal and ascending colonic tissue showed a comparably high expression level. These results suggest that there is already a maximal survivin expression under normal conditions. However, the intestine is able to maintain the regenerative capacity even in spite of an ischemic injury. These findings reflect the important relevance of an intact intestinal barrier.

摘要

背景

生存素是凋亡抑制蛋白(IAP)家族的成员之一,可调节有丝分裂和染色体分离。生存素在胚胎发育过程中表达,此外在癌细胞中也已得到证实。然而,也有证据表明生存素在包括成年大鼠胃肠道在内的分化组织中表达。一项对人类结肠标本的研究显示,正常黏膜的大多数隐窝基底上皮细胞中存在生存素。关于小肠中生存素表达的信息相当有限。为了更详细、完整地描绘胃肠道中生存素的表达模式,我们采用免疫组织化学方法对成年正常大鼠小肠和升结肠组织进行了研究。此外,为了更深入了解组织损伤后生存素表达的调控机制,我们还研究了其在肠系膜缺血再灌注(I/R)损伤中的表达。

方法

通过夹闭雄性Wistar大鼠(每组6只动物)的肠系膜上动脉90分钟,随后再灌注120分钟,诱导肠系膜缺血再灌注损伤。对未处理或经缺血处理的组织石蜡切片进行生存素和Ki-67染色的免疫组织化学评估。

结果

在常氧组的小肠和升结肠中可检测到生存素。它主要在上皮隐窝细胞中表达,在绒毛中仅有少量表达。所研究的各个小肠段显示出相当的染色强度。同样,在缺血损伤的小肠和升结肠中也检测到了生存素的表达。就现有组织损伤而言,其表达模式与常氧动物相似。作为细胞增殖标志物的Ki-67与生存素的表达模式比较显示,这两种蛋白在小肠和升结肠组织中存在共同定位。

结论

生存素在小肠和升结肠组织的上皮细胞中强烈表达。其表达位于具有高增殖率和再生能力的细胞中。这进一步支持了生存素在细胞分裂中的决定性作用。令人惊讶的是,缺血损伤的小肠和升结肠组织显示出相当高的表达水平。这些结果表明,在正常条件下生存素已经有最大表达。然而,即使遭受缺血损伤,肠道仍能够维持其再生能力。这些发现反映了完整肠屏障的重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d05/5471735/700eeac32f24/12876_2017_625_Fig1_HTML.jpg

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