中文摘要：

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0．5h腹腔内注射入PD98059，0．3mg.kg-1。于CLP处理后2h、4h,6h、8h，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2h开始升高，6h达高峰，8h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10d，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。

英文摘要：

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.