脓毒症大鼠心肌细胞Toll样受体4和炎症因子基因表达的变化及作用机制  

Changes in expressions of the myocardial Toll-like receptor 4, tumor necrosis factor-α and interleukin-6 mRNA in rat with sepsis

作　　者：尹海燕[1] 韦建瑞[2] 张锐[1] 叶小玲[1] 洪城[1] 黎宝红[1] 赵蔚诗[1] 江颖仪[1] 

机构地区：[1]广州市红十字会医院中心ICU,广东510220 [2]广州市红十字会医院中心CCU,广东510220

出　　处：《中国危重病急救医学》2009年第8期488-491,I0002,共5页Chinese Critical Care Medicine

基　　金：基金项目：广东省广州市医药卫生科技项目（2008-YB-049）

摘　　要：目的观察脓毒症大鼠心肌细胞凋亡的变化及与Toll样受体4（TLR4）、肿瘤坏死因子-α（TNF—α）及白细胞介素-6（IL-6）基因表达的关系；同时探讨谷氨酰胺（Gin）在脓毒症心肌损伤治疗中的保护作用。方法采用内毒素脂多糖（LPS）腹腔注射法制备脓毒症大鼠模型。将大鼠随机分为对照组、LPS组及Gln组，再分为术后0、6、12、24h亚组，每组6只。于相应时间点取心肌组织，采用逆转录一聚合酶链反应（RT—PCR）检测TLR4、TNF—α及IL-6的mRNA表达，并观察心肌组织病理学改变。结果LPS组大鼠心肌细胞凋亡程度增高。LPS组、Gln组各时间点心肌细胞TLR4、TNF—α及IL-6的mRNA表达均较对照组明显增加（P均〈0．05）。而Gin组心肌细胞凋亡程度较LPS组轻，各时间点TLR4mRNA表达均较LPS组升高幅度明显降低，且于12h、24h差异有统计学意义；TNF—αmRNA表达亦降低，于6h、24h差异有统计学意义；IL-6mRNA表达较LPS组升高幅度降低，且于12h差异有统计学意义（P均〈0．05）。结论TLR4信号转导基因及其调控细胞因子TNF-α、IL-6基因表达在脓毒症心肌细胞损伤的发生发展中起重要作用。Gin通过影响相关基因表达干预脓毒症心肌细胞的凋亡。Objective To investigate the relationship between apoptosis of myocardial cell in the rats with sepsis and the expressions of Toll-like receptor 4 （TLR4）, tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） mRNA, and the protective effect of glutamine （Gln） against apoptosis of myocardial cell. Methods Rat model of sepsis was reproduced by peritoneal injection with lipopolysaecharide （LPS）, and the animals were divided into control group, LPS group and Gin group. Rats in each group were further divided into four subgroups, 0, 6, 12 and 24 hours （n= 6）. Apoptosis of myocardial cells was surveyed, and TLR4, TNF-α and IL-6 mRNA expressions were assessed with reverse transeription-polymerase chain reaction （RT-PCR）. The pathological changes in myocardial cells were observed. Results Myocardial apoptosis rate in LPS group was higher. Compared with the control group, expressions of TLR4 mRNA, TNF-α mRNA and IL-6 mRNA were significantly higher at all time points after LPS administration in the LPS group and the Gin group （all P〈0. 05）. Compared with the LPS group, the rate of myocardial apoptosis in Gln group was lower, and expression of TLR4 mRNA in the Gln group was significantly lower at 12 hours and 24 hours ; the expression of TNF-α mRNA was obviously lower at 6 hours and 24 hours ; the expression of IL-6 mRNA in the Gin group was significantly lower at 12 hours （all P〈0. 05）. Conclusion TLR4, TNF-α and IL-6 gene expressions play extremely important role in apoptosis of myocardial cell in the rat with sepsis. Gin can affect apoptosis-related gene expressions, thus alleviating the apoptosis of myocardial cell.

关 键 词：脓毒症 谷氨酰胺 TOLL样受体4 细胞因子 

分 类 号：R686[医药卫生—骨科学]