创伤性脑损伤后肠黏膜细胞凋亡和c-fos基因表达

Apoptosis and c-fos expression in the rat gut mucosa following traumatic brain injury

目的:研究创伤性脑损伤(TB I)后小肠黏膜细胞凋亡及c-fos基因表达,探讨肠黏膜上皮细胞凋亡在破坏肠黏膜屏障中的作用及c-fos基因表达与凋亡的关系。方法:雄性W istar大鼠,随机分为假手术(对照)组和脑创伤后3 h、12 h、24 h、72 h和7 d组,采用自由落体撞击致重型颅脑损伤。在各时相点取空肠近端,应用TUNEL法观测小肠黏膜细胞凋亡,应用免疫组化法观察c-fos基因的表达。结果:①凋亡细胞以肠黏膜上皮细胞为主;②脑损伤后3 h肠黏膜上皮即出现明显凋亡,凋亡细胞的数量以伤后72 h最多,分布于绒毛顶端,后延伸至绒毛中下部;③脑损伤后肠黏膜上皮细胞的c-fos基因表达逐渐增强,主要出现在上皮细胞、平滑肌细胞和淋巴细胞,伤后24 h、72h和7d的表达明显升高。结论:创伤性脑损伤可引起大鼠小肠黏膜细胞明显凋亡和c-fos基因的显著表达。

Objective：The aim is to study the apoptosis and c-fos expression occurred in the rat gut following traumatic brain injury, and to explore the potential role of mucosal apoptosis in the intestinal barrier dysfunction and the relation of c-fos expression withthe mucosal apoptosis. Methods ： Male Wistar rats were randomly divided into six groups （6 rats each group） including controls with sham operation and TBI groups at hours 3, 12, 24, and 72, and on day 7. Parietal brain contusion was adopted using weight-dropping method. Rat jejunum was taken at each corresponding time point. Apoptosis was detected by in situ immunohistochemical staining （TUNEL） and c-fos expression by immunohistochemistry. Results：Mucosal epithelium appeared to be the major apoptotic cells, and the number of apoptotic cells increased since 3 h after TBI, peaking at 72 h postinjury. The apoptotic cells initially located at the tip of villus and gradually spread to the whole villus. The c-fos expression of gut mucosa gradually increased after TBI, predominantly in epithelial ceils, smooth muscle ceils and lymphocytes and with the maximal expression appeared at 24 h, 72 h and 7 d postinjury. Conclusion：It is highly suggested that intestinal mucosa apoptosis plays an important role in the pathogenesis of gut barrier damage, and c-fos expression might be highly responsible for the apoptosis, proliferation and renovation of the small intestinal mucosa.