初探低氧暴露对大鼠胃肠道ghrelin信号通路的影响
首发时间:2015-06-24
摘要:目的:通过过低氧暴露对大鼠胃肠ghrelin信号通路的影响,初探低氧刺激对消化系统的影响机制。方法6周龄Wistar大鼠24只称重后随机分为4组,分别为普通对照组(NC)、低氧12h组(H-12)、低氧24h组(H-24)和低氧48h组(H-48),每组6只。低氧组动物分别在人工模拟10.2%氧气浓度(相当于5000米海拔氧含量)中暴露12h、24h和48h。干预结束后所有动物麻醉后腹主动脉取血,采集胃底部和十二指肠、垂体和下丘脑组织,使用蛋白质芯片测试大鼠胃肠组织炎症因子含量,使用实时荧光定量PCR法测试胃肠组织ghrelin mRNA、垂体下丘脑组织GHS-R mRNA表达水平。所有数据以平均数±标准差(X ?±SD)表示。结果:(1)大鼠体重随急性低氧暴露时间延长呈显著下降趋势。(2)低氧暴露12h后胃组织TNF-α、IL-10、IL-2等指标表达显著上升,随着暴露时间的增加,TNF-α、IL-10、IL-2等指标逐渐回落到低氧干预前水平。低氧暴露后肠道TNF-α、IL-10、IL-2等指标表达水平显著下降,并于暴露24h后达到最低值,随后于暴露48h回升至低氧干预前水平。(3)胃ghrelin mRNA表达水平在低氧暴露12h后出现显著下降(P<0.05)然后出现回升并超过对照组的表达水平;肠道ghrelin mRNA表达水平在低氧暴露后变化趋势与胃组织相近;垂体GHS-R mRNA表达水平在低氧暴露12h后出现显著下降(P<0.05)之后随着暴露时间的增加GHS-R mRNA表达水平出现回升但是没有达到对照组GHS-R mRNA表达水平;下丘脑GHS-R mRNA表达水平总体变化趋势与垂体GHS-R mRNA表达水平趋势相近,但是表达水平回升相对滞后。结论:急性低氧暴露对胃肠道的不适反应可能是通过Ghrelin-GHS-R反应来影响消化系统功能异常的机制之一。
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Effect of Acute Hypoxia Exposure on Ghrelin Signal Pathway in Rats
Abstract:Object: the aim of this study was to preliminary investigate the change of the ghrelin signal pathway in rats' gastric and intestinal tissue under the intervention of acute hypoxia exposure, so as to explore the mechanism of abnormalities of the digestive system caused by hypoxia exposure. Methodology: 24 Wistar male rats were randomly divided into group NC (normal control, 6), group H-12 (hypoxia 12h, 6), group H-24 (hypoxia 24h, 6) and group H-48 (hypoxia 48h, 6). All rats were fed normal chow with free drinking water. Rats in hypoxia group were placed in normobaric hypoxia, and controls remained in room air. Rats were killed at 12h, 24h and 48h of hypoxia intervention and then detect the indicators. Body weight were recorded before and after the intervention. The mRNA level of ghrelin in gastric and intestinal tissue and GHS-R mRNA level in the pituitary and hypothalamus were detected by using Real Time PCR. And inflammatory factors were detected by a protein chip. Results: the body weight trend downward after hypoxia exposure. Inflammatory factors like TNF-α, IL-10, IL-2 etc. increased significantly in gastric tissue in H-12 and gradually decreased as exposure time increased. While in intestinal tissue, inflammatory factors significantly decreased and reached its minim level in H-24 then show trend rebound in H-48. Ghrelin mRNA level in gastric tissue were significantly decreased (P<0.05) in H-12, and show trend rebound in H-24 and H-48. The ghrelin mRNA level in intestinal tissue shows same tendency as in gastric tissue. Pituitary GHS-R mRNA level decreased significantly (P<0.05) in H-12and rebound slightly in H-24 and H-48. The tendency of GHS-R level in hypothalamus was similar to the pituitary, but lagged. Conclusion: the diversification to ghrelin and GHS-R mRNA level caused by acute hypoxia exposure might be one of the mechanism how hypoxia affect the digestive system.
Keywords: Biochemistry Hypoxia Exposure ghrelin
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