摘要
目的观察肠道缺血／再灌注（I／R）的淋巴液对炎性因子和Toll样受体4（TLR4）的配体高迁移率族蛋白B1（HMGB1）的影响。方法收集淋巴液，SD大鼠20只，体重（300±20）g，分为淋巴液引流组（N组，只引流淋巴液180min）和肠道I／R淋巴液引流组（I／R组，引流淋巴液180min同时夹闭肠系膜上动脉60min后复灌120min）。TLR4基因缺陷（TLR4^-/-）小鼠和野生型小鼠（C57BL／6）各32只，分别分为4个亚组（n=8），从尾静脉注射不同成分。N组：注射普通淋巴液；I／R组：注射I／R的淋巴液；Edt组：注射内毒素；HMGB1组：注射HMGB1蛋白。180min后取材。结果大鼠肠道I／R时，I／R组引流的淋巴液中内毒素和HMGB1显著高于普通引流组[内毒素：（Q034±0．050）Eu／ml比（0．017±0．023）Eu／ml，P=0．033；HMGB1：（4．293±0．883）ng／ml比（0．509±0．128）ng／ml，P=0．006]。TLR4^-/-小鼠和野生型小鼠在注射不同成分后，注射HMGB1的野生型小鼠比HMGB1的TLR4^-/-小鼠回肠黏膜厚度（TLR4^-/-比野生型小鼠：（602．1±37．5）μm比（335．8±43．2）μm，P=0．000]和绒毛高度[（404．5±18．6）μm比（273．0±31．7）μm，P=0．000]显著降低；注射I／R淋巴液的二组黏膜厚度和绒毛高度都有所降低，但TLR4^-/-组比野生型组小鼠黏膜厚度和绒毛高度的降低显著减少；注射普通淋巴液和内毒素的TLR4^-/-与野生型小鼠之间血清细胞因子白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α、内毒素和HMGB1差异无统计学意义。注射I／R淋巴液的TLR4^-/-组的炎症因子水平显著低于其野生型小鼠组[TLR4^-/-比野生型，TNF-α：（28．637±5．166）pg/ml比（41．917±8．175）pg／ml，P=0．000；IL-6：（60．900±24．729）pg／ml比（110．265±28．545）pg／ml，P=0．000]；注射HMGB1的TLR4^-/-组的炎性因子浓度显著低于野生型小鼠组[TLR4^-/-比野生型小鼠，TNF-α：（20�
Objective To investigate the effects of lymph from ischemic/reperfused intestine on the in flammatory factors and Toll-like receptor 4 （TLR4） ligand high mobility group box-1 （HMGB1） in TLR4 deficient （TLR4^ -/- ） mice. Methods A total of 20 SD rats weighing （300 ± 20） g were randomly assigned into two groups： lymph drainage group （group N, lymph drainage for 180 minutes without other treatment） and intestinal ischemia/reperfusion group （group I/R, draining the lymph for 180 minutes while clipping the superiormesenteric artery for 60 minutes followed by 120-minute reperfusion）. Thirty-two TLR4^ -/- mice and thirty-two C57BL/6 wild type （WT） mice were each divided into 4 sub-groups （ n = 8 ）, injected with different fluids through the caudal vein： group N with normal lymph; group I/R with I/R lymph; group Edt with endotoxin; group HMGB1 with HMGB1 protein. The mice were sacrificed 180 minutes after the injection for sample collection. Results The levels of endotoxin and HMGB1 in the lymph drainage of the group I/R rats were significantly higher than that of the group N rats [ （ 0. 034 ± 0. 050 ） Eu/ml vs. （ 0. 017 ± 0. 023 ） Eu/ml, P = 0.033; （4.293 ±0.883） ng/ml vs. （0.509 ±0.128） ng/ml, P =0.006]. In the mice injected with HMGB1, the mucosa thickness and villus height in the ileum of the WT mice were significantly lower than that of the TLR4^-/-mice [ （335.8±43.2） μm vs. （602. 1 ±37.5） μm, P=0.000; （273.0 ±31.7） μm vs. （404. 5 ± 18.6）μm, P =0. 000] ; in both WT and TLR4^-/- mice injected with the I/R lymph drainage, the mucosa thickness and villus height were decreased, but the decrements were significantly lower in TLR4^-/- mice; there were no statistically significant differences in the levels of interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, endotoxin, and HMGB1 between the TLR4^-/- and the WT mice injected with normal lymph or endotoxin. In the mice injected with I/R lymph drainage, the levels of inflammatory f
出处
《中华临床营养杂志》
CAS
CSCD
2015年第3期164-169,共6页
Chinese Journal of Clinical Nutrition
基金
国家自然科学基金（30940069）
北京市自然科学基金（7102127）
