摘要
目的通过动物脓毒症模型探讨可溶性髓样细胞触发受体(sTREM-1)与Janus激酶-信号转导和转录激活因子(JAK/STAT)通路的关系。方法采用盲肠结扎穿孔(CLP)法制作大鼠脓毒症模型,大鼠随机(随机数字法)分为正常对照组(n=6)。假手术组(n=24)、CLP组(n=48)、JAK2抑制剂(AG490)组(n=48)和STAT3抑制剂(雷帕霉素,RPM)组(n=48)。留取外周血行流式细胞仪分析CD4+CD25+Treg细胞/CD4+T细胞比值.采厢逆转录多聚酶链式反应(RT-PCR)测定肝组织sTREM-1mRNA表达水平。结果CLP后6h肝sTREM-1mRNA表达即高于对照组和假手术组,且随时间变化逐渐升高。AG490组肝组织sTREM-1mRNA的表达任术后6h、24h(1.572±0.051,2.063±0.025)较同时间点CLP组(1.592±0.036,2.082±0.021)差异无统计学意义(P〉0.05),而在48h和72hAG490组肝组织sTREM-1mRNA的表达(2.522±0.083,3.153±0.021)低于同时间点CLP组(2.592±0.055,3.204±0.013)(P〈0.05)。术后6hRPM组肝组织sTREM-1mRNA的表达(1.581±0.017)较CLP组差异无统计学意义(P〉0.05),而在术后24、48、72hRPM组肝组织sTREM-1mRNA的表达(1.486±0.019,1.263±0.011,1.115±0.022)显著低于同时间点CLP组肝组织sTREM-1mRNA的表达(P〈0.05)。结论sTREM-1因子与JAK/STAT通路有关,阻断JAK/STAT通路能够抑制sTREM-1mRNA的表达,减缓脓毒症炎症反应的进展。
Objective To investigate the correlation between the soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in rats with abdominal sepsis. Methods Using a sepsis model produced by cecal ligation and puncture (CLP) , Wistar rats were randomly (random number) divided into normal control group (n = 6), sham-operated group ( n = 24, ) CLP group ( n = 48 ) , AG490 (JAK2 inhibitor) treatment group ( n = 48) and rapamycin (RPM , STAT3 inhibitor) treatment group (n = 48). At different intervals, the rats in each group were sacrificed, then the peripheral blood cells were harvested to detect the percent of CD4 + CD25 + Treg cells in CD4 + cells by flow cytometry. Meanwhile, mRNA of sTREM-1 from the tissue samples of the liver was also measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). Results Colnpared withthe normal control group and the sham-operated group, expression of sTREM-1 in the CLP group was significantly higher, and it showed a gradually increased tendency over time. At 6 and 24 hours, there were no significant differences in the expressions of sTREM-1 between the AG490 group ( 1. 57± 0. 051, 2. 063 ±0. 025, respectively) and the CLP group (1. 592 ±0. 036, 2. 082±0. 021, respectively). But the expression of sTREM-lin the AG490 group (2. 522 ± 0. 083, 3. 153 ±0. 021, respectively) was lower than those in the CLP group (2. 592 ±0. 055, 3. 204 ±0. 013, respectively) during 48 and 72 hours. In addition, there was no significant difference in the expression of sTREM-I between the RPM group (1. 581 ±0.017) and the CLP group ( 1. 592±0. 036) at 6 hours. And the expression of sTREM-lin the RPM group (1. 486 ±0. 019, 1. 263±0. 011, 1.115 ±0. 022, respectively) was significantly lower than those in the CLP group (2. 082 ±0. 021, 2. 592 ± 0. 055, 3. 204± 0. 013, respectively) during 24 to 72 hours. Conclusions These data proved that blocking JAK/STAT pathway could inhibit the expression of sTREM-1 and decelarate the progress of inflammatory reaction in rats with abdominal sepsis.
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2016年第3期314-319,共6页
Chinese Journal of Emergency Medicine
基金
国家临床重点专科建设项目(2011873)