Lambert G P, Gisolfi C V, Berg D J, Moseley P L, Oberley L W, Kregel K C
Department of Exercise Science, The University of Iowa, Iowa City, Iowa 52242-1111, USA.
J Appl Physiol (1985). 2002 Apr;92(4):1750-61; discussion 1749. doi: 10.1152/japplphysiol.00787.2001.
The purpose of this study was to characterize intestinal permeability changes over a range of physiologically relevant body temperatures in vivo and in vitro. Initially, FITC-dextran (4,000 Da), a large fluorescent molecule, was loaded into the small intestine of anesthetized rats. The rats were then maintained at approximately 37 degrees C or heated over 90 min to a core body temperature of approximately 41, approximately 41.5, or approximately 42.5 degrees C. Permeability was greater in the 42.5 degrees C group compared with the 37, 41, or 41.5 degrees C groups. Histological analysis revealed intestinal epithelial damage in heated groups. Everted intestinal sacs were then used to further characterize hyperthermia-induced intestinal permeability and to study the potential role of oxidative and nitrosative stress. Increased permeability to 4,000-Da FITC-dextran in both small intestinal and colonic sacs was observed at a temperature of 41.5-42 degrees C compared with 37 degrees C, along with widespread intestinal epithelial damage. Administration of antioxidant enzyme mimics or a nitric oxide synthase inhibitor did not reduce permeability due to heat stress, and tissue concentrations of a lipid peroxidation product were not altered by heat stress, suggesting that oxidative and nitrosative stress were not likely mediators of this phenomenon in vitro. In conclusion, hyperthermia produced increased permeability and marked intestinal epithelial damage both in vivo and in vitro, suggesting that thermal disruption of epithelial membranes contributes to the intestinal barrier dysfunction manifested with heat stress.
本研究的目的是在体内和体外一系列生理相关体温范围内表征肠道通透性的变化。最初，将一种大的荧光分子异硫氰酸荧光素标记的葡聚糖（4000道尔顿）注入麻醉大鼠的小肠。然后将大鼠维持在约37℃，或在90分钟内加热至核心体温约41℃、约41.5℃或约42.5℃。与37℃、41℃或41.5℃组相比，42.5℃组的通透性更高。组织学分析显示加热组存在肠道上皮损伤。然后使用外翻肠囊进一步表征热诱导的肠道通透性，并研究氧化应激和亚硝化应激的潜在作用。与37℃相比，在41.5 - 42℃时，小肠和结肠囊对4000道尔顿异硫氰酸荧光素标记的葡聚糖的通透性增加，同时伴有广泛的肠道上皮损伤。给予抗氧化酶模拟物或一氧化氮合酶抑制剂并不能降低热应激导致的通透性，热应激也未改变脂质过氧化产物的组织浓度，这表明氧化应激和亚硝化应激在体外不太可能是这种现象的介导因素。总之，高温在体内和体外均导致通透性增加和明显的肠道上皮损伤，表明上皮细胞膜的热破坏导致了热应激时出现的肠道屏障功能障碍。
