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孕酮对雄性大鼠创伤性脑损伤后肠道炎症反应、黏膜结构改变及细胞凋亡的影响。

Effects of progesterone on intestinal inflammatory response, mucosa structure alterations, and apoptosis following traumatic brain injury in male rats.

作者信息

Chen Gang, Shi Ji-Xin, Qi Meng, Wang Hu-Xu, Hang Chun-Hua

机构信息

Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.

出版信息

J Surg Res. 2008 Jun 1;147(1):92-8. doi: 10.1016/j.jss.2007.05.029. Epub 2007 Sep 14.

Abstract

BACKGROUND

Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes, and apoptosis in the gut. Progesterone given after TBI has been shown to reduce the cerebral inflammation and neuronal apoptosis in the brain. However, the effects of progesterone on the inflammatory response, structure alterations, and apoptosis in the intestinal mucosa following TBI has not been investigated.

MATERIALS AND METHODS

Right parietal cortical contusion in male rats was made by using the weight-dropping method. Rats were given 0 or 16 mg/kg injections of progesterone at postinjury at 1 and 6 hours and on days 1, 2, 3, 4, and 5. Gut samples were extracted at 5 days after trauma. We measured the concentrations of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay; intercellular adhesion molecule-1 expression by immunohistochemistry; intestinal mucosal morphological changes by histopathological study and electron microscopy; and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining.

RESULTS

Administration of progesterone following TBI could decrease the intestinal concentrations of IL-1beta and tumor necrosis factor-alpha, but not IL-6. The level of intercellular adhesion molecule-1 expression in the gut was down-regulated by progesterone. TBI-induced damages of gut structure and apoptosis were attenuated after progesterone injections.

CONCLUSIONS

The results of the present study suggest that post-TBI progesterone administration could suppress the intestinal inflammation, protect the intestinal mucosal structure, and reduce the mucosa apoptosis.

摘要

背景

创伤性脑损伤(TBI)可引发肠道持续的炎症反应、组织病理学变化及细胞凋亡。TBI后给予孕酮已显示可减轻脑部的炎症和神经元凋亡。然而,孕酮对TBI后肠黏膜炎症反应、结构改变及细胞凋亡的影响尚未得到研究。

材料与方法

采用重物坠落法对雄性大鼠造成右顶叶皮质挫伤。大鼠在伤后1小时、6小时以及第1、2、3、4和5天给予0或16mg/kg的孕酮注射。在创伤后5天提取肠道样本。我们通过酶联免疫吸附测定法测量白细胞介素-1β(IL-1β)、肿瘤坏死因子-α和白细胞介素-6(IL-6)的浓度;通过免疫组织化学检测细胞间黏附分子-1的表达;通过组织病理学研究和电子显微镜观察肠黏膜形态变化;并通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色检测细胞凋亡。

结果

TBI后给予孕酮可降低肠道中IL-1β和肿瘤坏死因子-α的浓度,但对IL-6无影响。孕酮可下调肠道中细胞间黏附分子-1的表达水平。注射孕酮后,TBI诱导的肠道结构损伤和细胞凋亡得到减轻。

结论

本研究结果表明,TBI后给予孕酮可抑制肠道炎症,保护肠黏膜结构,并减少黏膜细胞凋亡。

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