Impact of Pioglitazone on Macrophage Dynamics in Adipose Tissues of Cecal Ligation and Puncture-Treated Mice
Impact of Pioglitazone on Macrophage Dynamics in Adipose Tissues of Cecal Ligation and Puncture-Treated Mice
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DOI：
10.1248/bpb.b16-00883
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发表时间：
2017-05-01
影响因子：
2
通讯作者：
Uchida, Eiji
中科院分区：
文献类型：
--
作者：
Matsutani, Takeshi;Tamura, Kazuhiro;Uchida, Eiji
吡格列酮改善脓毒症诱导的器官损伤，并对内脏脂肪组织具有抗炎作用。然而，其在脂肪免疫细胞中的作用仍有待确定。我们研究了吡格列酮对盲肠结扎穿孔（CLP）诱导的脓毒症小鼠内脏脂肪巨噬细胞群和极化的影响。将8周龄雄性小鼠分为3组：1）假手术组，2）CLP组，或3）吡格列酮治疗CLP组。腹腔注射吡格列酮（10 mg/kg）7 d后行CLP手术。术后24 h取内脏脂肪组织。通过实时RT-PCR定量几种巨噬细胞标志物（M1的诱导型一氧化氮合酶（iNOS）、M2的谷胱甘肽转移酶1（Arg 1）和白细胞介素（IL）-10、成熟巨噬细胞的CD 163和F4/80）和炎性脂肪因子（IL-6、单核细胞趋化蛋白-1：MCP-1）的mRNA表达。组织切片进行免疫组化分析和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）测定。CLP组Arg 1、IL-10和iNOSmRNA表达较假手术组显著增加，吡格列酮组CD 163和F4/80 mRNA表达较假手术组显著增加。吡格列酮治疗可降低CLP刺激的IL-6和MCP-1的表达。CLP组和吡格列酮组CD 11b/c和CD 163阳性细胞以及凋亡细胞增加。数据表明，在CLP诱导的小鼠中，内脏脂肪组织的M1/M2巨噬细胞活化被诱导，并且从周围器官募集的巨噬细胞的功能可以通过吡格列酮处理来调节。
Pioglitazone improves sepsis-induced organ injury accompanied with anti-inflammatory effects on visceral adipose tissue. However, its action in adipose immune cells remains to be ascertained. We investigated the effects of pioglitazone on visceral adipose macrophage population and polarisation in cecal ligation and puncture (CLP)-induced sepsis mice. Eight-week-old male mice were assigned to 3 groups: 1) sham-operated group, 2) CLP group, or 3) pioglitazone-treated CLP group. Pioglitazone (10 mg/kg) was injected intraperitonally for 7d and CLP surgery was performed. Visceral adipose tissues were collected 24h after the surgery. mRNA expression of several macrophage markers (inducible nitric oxide synthase (iNOS) for M1, arginase1 (Arg1) and interleukin (IL)-10 for M2, CD163 and F4/80 for mature macrophages) and inflammatory adipokines (IL-6, monocyte chemoattractant protein-1: MCP-1) was quantified by real-time RT-PCR. Tissue sections were subjected to the immunohistochemical analysis and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. CLP significantly enhanced Arg1, IL-10 and iNOS mRNA expressions as compared with the sham group, and pioglitazone significantly increased the mRNA level of CD163 and F4/80 in CLP mice. Expression of IL-6 and MCP-1 stimulated by CLP was reduced by pioglitazone treatment. Increased CD11b/c- and CD163-positive cells as well as apoptotic cells were observed in the CLP group and the pioglitazone-treated group. The data indicate that M1/M2 macrophage activation of visceral adipose tissues is induced in CLP-induced mice, and the function of macrophages recruited from surrounding organs may be modulated by pioglitazone treatment.