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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 neonatal rats with sepsis and the effect of extracellular signal-regulated kinase (ERK) inhibitor PD98059 on it. Methods The cecal ligation and perforation (CLP) was used to establish a neonatal rat model of sepsis. Totally 74 neonatal rats of 10 days old were randomly divided into control group (6 mice), CLP group (34 mice) and PD98059 group (34 mice). CLP group only CLP measures, PD98059 group of neonatal rats before CLP 0.5 h intraperitoneal injection of PD98059, 0.3 mg · kg-1. At 2 h, 4 h, 6 h and 8 h after CLP treatment, 6 neonatal rats were sacrificed in CLP group and PD98059 group, respectively. The brain tissue was removed and the expression of TNF-α protein in brain tissue was detected by enzyme-linked immunosorbent assay Reverse transcription PCR was used to detect the mRNA expression. Results In the control group, the expression of TNF-αmRNA and TNF-αprotein were only slightly expressed in the brain tissue of neonatal rats. The expression of TNF-αmRNA and its protein in brain tissue of CLP rats increased at 2 h after CLP treatment, reached the peak at 6 h, decreased at 8 h, and were significantly higher than that of the control group (P <0.001, 0.05). The expression of TNF-α mRNA and protein in PD98059 group was significantly lower than that in CLP group at each time point (Pa <0.001, 0.05). On the 10th day of experiment, a total of 10 neonatal rats in the CLP group and the PD98059 group were sacrificed and 10 rats died. Eight of them died in the CLP group, with a mortality rate of 80% (8/10). Two of the PD98059 patients died with a mortality rate of 20% (2/10). There was significant difference in mortality between the two groups (P = 0.023). Conclusion Neonatal rat sepsis early brain tissue inflammatory cytokines TNF-α expression increased, while ERK inhibitor PD98059 down-regulated its expression, relieve brain injury and reduce its mortality.