Effects of histone methyltransferase inhibitor on the polarization of peritoneal macrophages in septic mice
10.3760/cma.j.issn.2095-4352.2019.02.013
- VernacularTitle:组蛋白甲基转移酶抑制剂对脓毒症小鼠?腹腔巨噬细胞极化的影响
- Author:
Qianqian ZHANG
1
;
Xiaohui ZHOU
;
Lunxian TANG
Author Information
1. 同济大学附属东方医院急诊内科
- Keywords:
Sepsis;
Macrophage polarization;
Histone methyltransferase EZH2;
Peroxisome proliferator-activated receptorγ
- From:
Chinese Critical Care Medicine
2019;31(2):187-192
- CountryChina
- Language:Chinese
-
Abstract:
Objective? To?investigate?the?effect?of?histone?methyltransferase?(EZH2)?inhibitor?on?the?polarization??of?peritoneal?macrophages?in?septic?mice.? Methods? Thirty-six?healthy?male?C57BL/6J?mice?were?divided?into?three?groups?by?random?number?table?method?(n?=?12):?sham?operated?group?(Sham?group),?sepsis?model?group?(CLP?group)??and?EZH2?inhibitor?treatment?group?(CLP+3-DZNeP?group).?Sepsis?animal?model?was?established?by?cecum?ligation?and?puncture?(CLP);?Sham?group?was?challenged?only?by?cecum?traction?without?ligation.?3-Deazaneplanocin?A?(3-DZNeP)?1?mg/kg?was?intraperitoneal?injected?24?hours?before?and?1?hour?after?CLP?in?CLP+3-DZNeP?group.?Eight?mice?in?each?group?were?sacrificed?at?24?hours?after?surgery.?The?levels?of?proinflammatory?cytokines?interleukin-6??(IL-6)?and?tumor?necrosis?factor-α(TNF-α)?in?peritoneal?lavatory?fluid?were?detected?by?high?throughput?liquid?protein?chip.?The?expression?levels?of?inducible?nitrogenase?(iNOS)?and?macrophage?mannose?receptor?(CD206)?were?analyzed?by?flow?cytometry.?Mouse?peritoneal?macrophages?were?isolated?and?purified?by?adherent?method,?the?protein?expressions?of?EZH2,?peroxisome?proliferator-activated?receptorγ(PPARγ)?were?detected?by?Western?Blot.?The?remaining?4?mice?? were?sacrificed?at?48?hours?after?surgery,?the?histopathological?changes?of?lung?and?kidney?tissue?were?evaluated?by?hematoxylin-eosin?(HE)?staining.? Results? Compared?with?Sham?group,?the?infiltration?of?inflammatory?cells?in?lung?and?kidney?of?the?CLP?group,?the?levels?of?IL-6?and?TNF-α?in?peritoneal?lavatory?fluid?were?significant?increased??[IL-6?(ng/L):?7?794.75±405.56?vs.?78.63±74.09,?TNF-α(ng/L):?147.25±25.19?vs.?18.20±5.03,?both?P?
