细胞外信号调节激酶抑制剂PD98059对脓毒症新生大鼠脑组织肿瘤坏死因子-α表达的影响  

Effect of Extracellular Signal Regulated Kinase Inhibitor PD98059 on Expression of Tumor Necrosis Factor-α in Brain Tissue in Neonatal Rats with Sepsis

作　　者：王静[1] 李熙鸿[1] 屈艺[1] 刘忠强[1] 潘玲丽[1] 王炎[1] 王慧卿[1] 母得志[1] 

机构地区：[1]四川大学华西第二医院急诊医学科,成都610041

出　　处：《实用儿科临床杂志》2012年第24期1888-1890,共3页Journal of Applied Clinical Pediatrics

基　　金：教育部长江学者和创新团队发展计划(IRT0935);国家自然科学基金(30500544);四川省科技厅支撑项目(2012SZ0012)

摘　　要：目的探讨脓毒症新生大鼠脑组织炎性细胞因子TNF-α的表达水平及细胞外信号调节激酶(ERK)抑制剂PD98059对其表达的影响。方法行盲肠结扎穿孔术(CLP)建立脓毒症新生大鼠模型。将74只10日龄新生大鼠随机分为对照组(6只)、CLP组(34只)和PD98059组(34只)。CLP组只采用CLP措施,PD98059组新生大鼠于CLP处理前0.5 h腹腔内注射入PD98059,0.3mg·kg-1。于CLP处理后2 h、4 h、6 h、8 h,CLP组和PD98059组各取6只新生大鼠处死,取出脑组织,采用酶联免疫吸附试剂盒检测脑组织TNF-α蛋白的表达,反转录PCR检测其mRNA表达。结果对照组新生大鼠脑组织仅微量表达TNF-αmRNA及TNF-α蛋白。CLP组新生大鼠脑组织TNF-αmRNA及其蛋白的表达量于CLP处理后2 h开始升高,6 h达高峰,8 h下降,均明显高于对照组(P<0.001、0.05)。PD98059组各个时间点TNF-αmRNA及其蛋白的表达量均明显低于CLP组(Pa<0.001、0.05)。实验10 d,CLP组和PD98059组未处死的20只新生大鼠共有10只大鼠死亡。其中CLP组8只死亡,死亡率为80%(8/10);PD98059组死亡2只,死亡率为20%(2/10)。2组间死亡率比较差异有统计学意义(P=0.023)。结论新生大鼠脓毒症早期,脑组织中炎性细胞因子TNF-α表达上调,而ERK抑制剂PD98059可下调其表达,缓解脑损伤,降低其死亡率。Objective To investigate the expression of inflammatory cytokines TNF - α in brain tissue of rats with seps：is and the effect of extracellular signal regulated kinase （ERK） inhibitor PD98059 on its expression. Methods Models of neonatal rats with sepsis were estab- lished by the cecal ligation and puncture （ELP）. Totally 74 cases of 10 - day - old neonatal rats were randomly divided into 3 groups ： control group （n =6） ,CLP group （n =34） and PD98059 group （n =34）. In CLP group,only CLP was performed in the rats. In PD98059 group, PD98059 （0.3 mg . kg-1 body weight） was injected into the rats peritoneal cavity 0.5 hour before CLP. Six rats in CLP group and PD98059 group were killed and their brains were removed at 2 h ,4 h ,6 h and 8 h after CLP, respectively. Then, reverse transcriptase polymerase chain reaction was used to detect the TNF - α mRNA expression in rats＇ brain tissue. Expression of protein was detected by the enzyme linked im- munosorbent assay. Results In control group,there were very low expressions of TNF - α mRNA and protein in rats＇ brain tissue. In CLP group ,the expressions of TNF - α mRNA and protein started to increase at 2 hours ,reached the peak at 6 hours and decreased at 8 hours after C LP, and were up- regulated significantly compared with control group（ P 〈 0. 001,0.05 ）. Expressions of TNF-a mRNA and protein were significantly lower in various time points after CLP in PD98059 group than those in CLP group（ Pa 〈 0. 001,0.05 ）. Additionally, 10 cases in the other 20 rats with sepsis died in 10 days,including 8 cases in CLP group （mortality rate, 80% ） and 2 cases in PD98059 group （mortality rate,20% ） （ P = 0.023 ）. Conclusions In the early stage, sepsis can induce the prominent increased expression of TNF - α in brain tissue of neonatal rats. But ERK inhibitor PD98059 can down - regulate its expression, and alleviate the brain injury as well as reduce septic mortality.

关 键 词：脓毒症 细胞外信号调节激酶 PD98059 肿瘤坏死因子Α 新生大鼠 

分 类 号：R459.7[医药卫生—急诊医学]