脓毒血症时肾脏炎症因子的变化:以大鼠为实验动物的临床研究

Inflammatory factors in kidney early in sepsis: experiment with rats

目的研究脓毒血症时肾内肿瘤坏死因子-α（TNF-α）、MCP～1含量变化。方法48只SD大鼠随机分为等量的两组，一组接受盲肠结扎及贯穿以建立大鼠脓毒血症模型，分别在致伤后1h、3h、6h、12h、24h、48h采血，用全自动生化分析仪测定各时间点的血清尿素氮（BUN）、血肌酐（SCr）含量。随即将大鼠处死，取出肾脏，用碘化丙啶膜联蛋白V双染色法和流式细胞术检测细胞凋亡率。用ELISA法测定肾组织匀浆上清中的TNF—α、MCP-1含量。对照组24只只行假手术，分别在1h、3h、6h、12h、24h、48h后采血，并随即处死，取出肾脏。结果CLP致伤组各时间点肾组织匀浆中TNF-α、MCP-1水平均显著高于对照组（均P〈0．01），于致伤后3h达高峰。CLP致伤后1～3h肾组织匀浆细胞凋亡率显著升高，于致伤后3h达高峰，各时间点的细胞凋亡率均显著高于（均P〈0．01）。CLP组6h后各时间点的血尿素氮（BUN）、血肌酐（SCr）均显著高于对照组（均P〈0．01）。结论脓毒血症早期TNF-α和MCP-1即被激活，脓毒症引起的肾功能改变与细胞因子大量释放有关。

Objective To in observe the changes of inflammatory factors, tumor necrosis-ct （TNF-α） and monocyte chemotactic protein-1 （MCP-1） in kidney during early stage of sepsis and to investigate the relationship between these factors and acute renal dysfunction （ARF）. Methods Forty-eight SD rats were randomly divided into 2 equal groups： cecal ligation and puncture （CLP） group .undergoing CLP and collection of blood samples 1, 3, 6, 12, 24, and 48h later to examine the levels of blood urea nitrogen （BUN） and serum creainine （SCr）; and control group, undergoing sham operation and collection of blood samples 1, 3, 6, 12, 24, and 48h later to examine the levels of BUN and SCr Then the rats were killed with their kidneys taken out. Propidine iodide/annexin V staining and flow cytometry were used to detect the cell apoptosis. Renal homogenate was prepared. ELISA was used to examine the levels of TNF-α and MCP-1 in the supernatant of the renal homogenate. Results The TNF- α and MCP-1 levels in the renal homogenate at different time points of the CLP group were all significantly higher than those of the control group （all P〈0.01） with peak 3h later. The apoptotic rates at different time points of the CLP group were all significantly higher than those of the control group （all P〈0.01 ）And the serum BUN and Scr levels of the CLP groups were all significantly higher than those of the control group （all P〈0.01）. Conclusion TNF-α and MCP-1 are activated in the early stage of sepsis and are significantly related to the release of a grate deal of cytokines.