中性粒细胞sTLR9和IL-17在小鼠脓毒症性腹膜炎发病中的相关性研究
发布时间：2018-11-10 16:50
【摘要】：脓毒症的高致死率一直是临床急需解决的难题。为了研究脓毒症炎症局部的免疫细胞应答对疾病发生发展的影响,我们利用大肠杆菌腹腔注射的方法建立了小鼠脓毒症性腹膜炎模型,并观察了感染局部腹腔灌洗细胞(P LC)中的中性粒细胞(P MN)的数量、形态、亚群及活性的变化,发现:1)腹膜炎小鼠PLC中PMN的数量明显增多,出现巨大细胞,且与菌量正相关;2)PMN的两个亚群CD11b~+PMN和CD11b-PMN比例有差异,感染早期CD11b~+PMN降低而CD11b-PMN比例增高,随着病程延长,两群细胞比例均回归正常;3)虽然在感染18h时,C D11b~+PMN和CD11b-PMN中s TLR9+细胞比例均明显增高,但在感染的更早时间(8h),s TLR9表达水平增高主要出现在CD11b~+PMN,而高菌量组的CD11b-PMN表达s TLR9水平降低;4)作为炎症细胞因子的IL-17在感染早期(8h)的CD11b~+PMN和CD11b-PMN中的表达水平均明显增高,但在感染18h时似乎只有C D11b~+PMN还在分泌IL-17;5)对于CD11b~+PMN,s TLR9和IL-17的表达不在同一群细胞内,但二者的变化规律是一致的;6)免疫抑制性ODN能提高脓毒症腹膜炎小鼠的生存率,抑制P MN两个亚群s TLR9的表达水平,也抑制C D11b~+PMN的IL-17表达水平及T细胞和巨噬细胞IL-17的表达水平。值得注意的是:在本研究中,我们通过流式细胞分选法证明细菌感染局部I L-17的产生不仅来源于C D3+T细胞,也来源于PMN。我们的研究提示:PMN在细菌感染中发挥重要的作用,但不同P MN亚群的功能有差异,s TLR9+PMN及IL17+PMN在感染后病情发展中有重要作用,可能成为脓毒症干预治疗或预后预测的关注对象。
[Abstract]:The high mortality rate of sepsis is an urgent problem in clinic. In order to study the effect of local immune cell response of sepsis inflammation on the occurrence and development of the disease, we established a mouse model of septic peritonitis by intraperitoneal injection of Escherichia coli. The number, morphology, subgroup and activity of neutrophil (P MN) in (P LC) of infected local peritoneal lavage cells were observed. The results showed that: 1) the number of PMN in PLC of peritonitis mice increased obviously, and giant cells appeared. And positive correlation with the amount of bacteria; 2) the proportion of CD11b~ PMN and CD11b-PMN in two subsets of PMN was different. The proportion of CD11b~ PMN decreased but CD11b-PMN increased in the early stage of infection. With the prolongation of the course of disease, the proportion of CD11b~ PMN and CD11b-PMN returned to normal. 3) although the proportion of s TLR9 cells in C D 11b ~ PMN and CD11b-PMN increased significantly at 18 h, the increase of), s TLR9 expression at the early stage of infection (8 h) was mainly found in CD11b~ PMN, while the CD11b-PMN expression s TLR9 level in high bacteria group was decreased. 4) the expression of IL-17, as an inflammatory cytokine, was significantly increased in CD11b~ PMN and CD11b-PMN at the early stage of infection (8 h), but only C D 11b ~ PMN seemed to secrete IL-17; at 18 h after infection. 5) the expression of CD11b~ PMN,s TLR9 and IL-17 was not in the same group of cells, but the changes of them were consistent. 6) immunosuppressive ODN could increase the survival rate of mice with septic peritonitis, inhibit the expression of s TLR9 in two subsets of P MN, IL-17 expression of C D11b- PMN and IL-17 expression of T cells and macrophages. It is worth noting that, in this study, we demonstrated by flow cytometry that the local production of L-17 in bacterial infection was derived not only from C D3 T cells, but also from PMN.. Our results suggest that PMN plays an important role in bacterial infection, but the function of different P MN subsets is different. S TLR9 PMN and IL17 PMN play an important role in the development of disease after infection. It may be the focus of sepsis intervention therapy or prognosis prediction.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R459.7
[Abstract]:The high mortality rate of sepsis is an urgent problem in clinic. In order to study the effect of local immune cell response of sepsis inflammation on the occurrence and development of the disease, we established a mouse model of septic peritonitis by intraperitoneal injection of Escherichia coli. The number, morphology, subgroup and activity of neutrophil (P MN) in (P LC) of infected local peritoneal lavage cells were observed. The results showed that: 1) the number of PMN in PLC of peritonitis mice increased obviously, and giant cells appeared. And positive correlation with the amount of bacteria; 2) the proportion of CD11b~ PMN and CD11b-PMN in two subsets of PMN was different. The proportion of CD11b~ PMN decreased but CD11b-PMN increased in the early stage of infection. With the prolongation of the course of disease, the proportion of CD11b~ PMN and CD11b-PMN returned to normal. 3) although the proportion of s TLR9 cells in C D 11b ~ PMN and CD11b-PMN increased significantly at 18 h, the increase of), s TLR9 expression at the early stage of infection (8 h) was mainly found in CD11b~ PMN, while the CD11b-PMN expression s TLR9 level in high bacteria group was decreased. 4) the expression of IL-17, as an inflammatory cytokine, was significantly increased in CD11b~ PMN and CD11b-PMN at the early stage of infection (8 h), but only C D 11b ~ PMN seemed to secrete IL-17; at 18 h after infection. 5) the expression of CD11b~ PMN,s TLR9 and IL-17 was not in the same group of cells, but the changes of them were consistent. 6) immunosuppressive ODN could increase the survival rate of mice with septic peritonitis, inhibit the expression of s TLR9 in two subsets of P MN, IL-17 expression of C D11b- PMN and IL-17 expression of T cells and macrophages. It is worth noting that, in this study, we demonstrated by flow cytometry that the local production of L-17 in bacterial infection was derived not only from C D3 T cells, but also from PMN.. Our results suggest that PMN plays an important role in bacterial infection, but the function of different P MN subsets is different. S TLR9 PMN and IL17 PMN play an important role in the development of disease after infection. It may be the focus of sepsis intervention therapy or prognosis prediction.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R459.7
【相似文献】
相关期刊论文 前10条
1 姚咏明,盛志勇;脓毒症研究的若干新动态[J];中国危重病急救医学;2000年06期
2 菲琳;;治疗脓毒症的新希望[J];国外医学情报;2002年10期
3 向阳;防止脓毒症自高动力相转向低动力相的新途径[J];国外医学.外科学分册;2003年03期
4 任新生;重新认识全身炎症反应综合征、脓毒症和多器官功能衰竭综合征[J];中华急诊医学杂志;2004年02期
5 崔德健;探讨脓毒症诊断和治疗新策略[J];中国呼吸与危重监护杂志;2004年03期
6 林洪远;脓毒症诊断和治疗进展[J];中国实用外科杂志;2004年06期
7 汤耀卿;脓毒症的定义和诊断[J];临床外科杂志;2004年11期
8 王小平;脓毒症研究现状[J];实用临床医学;2005年06期
9 周国勇;性别与脓毒症严重程度的关系[J];中国危重病急救医学;2005年07期
10 黎永明;姜勇;;脓毒症发生机制的新进展[J];感染.炎症.修复;2005年01期
相关会议论文 前10条
1 张丽葳;奚希相;张威;张莉芬;陈昊;李俊;杨兴易;;以血小板减少为主要表现的脓毒症抢救一例[A];《中华急诊医学杂志》第八届组稿会暨急诊医学首届青年论坛论文汇编[C];2009年
2 张振辉;林s钜，
本文编号：2323010
本文链接：https://www.wllwen.com/yixuelunwen/jjyx/2323010.html
最近更新
教材专著
