白细胞介素-17 对脱氧皮质酮/ 盐诱导的高血压 心肌纤维化大鼠巨噬细胞极化的影响
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马礼坤,E-mail :lkma119@163.com ;Tel :0551-62283339

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2016 年安徽省科技攻关计划项目(No :1604a0802074)


Effect of interleukin-17 on macrophage polarization in myocardial fibrosis of DOC/salt hypertensive rats
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    摘要:

    目的 探讨脱氧皮质酮(DOC)/ 盐诱导的高血压心肌纤维化(MF)大鼠中白细胞介素-17(IL-17) 对巨噬细胞极化的作用。方法 30 只雄性清洁级SD 大鼠予右肾切除处理,术后用含0.1% 氯化钾和1% 氯 化钠的饮水灌胃2 周,随机分成对照组、DOC 组、DOC+IL-17 抗体组。使用尾套法测量大鼠动脉收缩压, 1 次/2 周;天狼猩红染色法检测心肌间质纤维化程度;免疫组织化学法观察心肌组织CD11c、CD206 表 达;逆转录聚合酶链反应检测诱导性一氧化氮合酶(iNOS)、精氨酸酶1(Arg1)mRNA 的表达;Western blotting 检测各组IL-17、iNOS 和Arg1 蛋白表达。结果 各组收缩压比较,差异有统计学意义(P <0.05)。 DOC 组心肌间质胶原面积/ 视野总面积比值较对照组增加(P <0.05);使用IL-17 抗体中和干预治疗后, DOC+IL-17 抗体组心肌间质胶原面积/ 视野总面积比值较DOC 组减少(P <0.05)。DOC 组iNOS、Arg1 mRNA 相对表达量和IL-17、iNOS、Arg1、CD11c、CD206 蛋白相对表达量较对照组升高(P <0.05),使用 IL-17 抗体中和后,DOC+IL-17 抗体组iNOS、Arg1 mRNA 相对表达量较DOC 组降低(P <0.05),IL-17、 iNOS、Arg1、CD11c 和CD206 蛋白相对表达量较DOC 组降低(P <0.05)。结论 DOC/ 盐诱导的高血压 大鼠MF 中巨噬细胞极化很可能与IL-17 有关。

    Abstract:

    Objective To investigate the effect of interleukin-17 (IL-17) on macrophage polarization in DOC/ salt hypertensive rats. Methods Thirty male right uninephrectomized SD rats were treated with 0.1%KCl and 1%NaCl in the drinking water for 2 weeks and randomly divided to three groups: vehicle control rats (CON group); DOC treated group (DOC group); DOC and IL-17 antibody treated group (DOC+ IL-17 antibody group). Systolic blood pressure (SBP) was measured biweekly using the tail-cuff method. The extent of myocardial interstitial fibrosis was analyzed by sirius red staining. CD11c and CD206 were analyzed by immunohistochemistry. Expressions of mRNA of inducible nitric oxide synthases (iNOS) and arginase 1 (Arg1) were determined by real time PCR.Western blotting assay was performed to detect the protein expression of IL-17, iNOS and Arg1. Results There was significant difference in systolic blood pressure among three groups (P < 0.05). The ratio of collagen area to total area of visual field in doc group was higher than that in control group (P < 0.05); after neutralization with IL-17 antibody, the ratio of collagen area to total visual field area in the doc + IL-17 antibody group was lower than that in the doc group (P < 0.05). The expression of iNOS and Arg1 mRNA and the expression of IL-17, iNOS, Arg1, CD11c and CD206 protein were increased in DOC group compared with CON group (P > 0.05). After neutralizing with IL-17 antibody, the expression of iNOS and Arg1 mRNA in DOC+IL-17 antibody group was significantly lower than that of the DOC group (P < 0.05), and the expression of IL-17, iNOS, Arg1, CD11c and CD206 protein was decreased (P < 0.05). Conclusions Macrophage polarization is likely to be associated with IL-17 in DOC/salt hypertensive rats.

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周俊岭,范彬,马礼坤.白细胞介素-17 对脱氧皮质酮/ 盐诱导的高血压 心肌纤维化大鼠巨噬细胞极化的影响[J].中国现代医学杂志,2019,(24):15-21

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  • 收稿日期:2019-06-25
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  • 在线发布日期: 2019-12-30
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