Baicalin improves survival in a murine model of polymicrobial sepsis via suppressing inflammatory response and lymphocyte apoptosis.

Baicalin improves survival in a murine model of polymicrobial sepsis via suppressing inflammatory response and lymphocyte apoptosis.
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黄芩苷通过抑制炎症反应和淋巴细胞凋亡来提高多种微生物败血症小鼠模型的存活率。

DOI:
10.1371/journal.pone.0035523
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Li J
Li J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhu J;Wang J;Sheng Y;Zou Y;Bo L;Wang F;Lou J;Fan X;Bao R;Wu Y;Chen F;Deng X;Li J

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严重的炎症和淋巴细胞凋亡之间的失衡是脓毒症患者高死亡率的主要原因。黄芩苷是黄芩的主要活性成分,在炎症性疾病和感染性疾病中具有抗炎、抗细胞凋亡、甚至抗菌作用。然而,黄芩苷治疗多菌败血症的疗效尚不清楚。采用盲肠结扎穿刺法(CLP)建立C57BL/6小鼠多菌败血症模型。分别于CLP后1 h、6 h和12 h给予小鼠腹腔注射黄芩苷。在随后的8天内评估存活率。计算血液和腹膜腔内细菌载量,以评估细菌清除情况。计算腹腔灌洗液中中性粒细胞计数。苏木精-伊红染色观察肺、肝组织损伤情况。采用双抗体夹心酶联免疫吸附试验检测血清和腹膜组织中肿瘤坏死因子α、白介素6、白介素10和白介素17等细胞因子的水平。通过胸腺淋巴细胞的凋亡和脾中不同类型细胞的计数来评估获得性免疫功能。黄芩苷可显著提高脓毒症小鼠的细菌清除率和存活率。黄芩苷可降低小鼠腹腔灌洗液中中性粒细胞的数量。黄芩苷处理的小鼠肺和肝脏的中性粒细胞浸润减少与这些器官的损伤减轻有关。黄芩苷显著降低血液和腹膜促炎细胞因子的水平,而增加抗炎细胞因子的水平。胸腺中CD3+T细胞的凋亡受到抑制。与CLP组比较,黄芩苷组小鼠外周血中CD4+、CD8+T淋巴细胞和树突状细胞(DC)数量增加,而CD4+CD25+调节性T细胞数量减少。黄芩苷可提高多菌败血症小鼠的存活率,其机制可能与其抗菌、抗炎、抗细胞凋亡作用有关。
An imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3+ T cell was inhibited in the thymus. The numbers of CD4+, CD8+ T lymphocytes and dendritic cells (DCs) were higher, while the number of CD4+CD25+ regulatory T cells was lower in the baicalin group compared with the CLP group. Baicalin improves survival of mice with polymicrobial sepsis, and this may be attributed to its antibacterial property as well as its anti-inflammatory and anti-apoptotic effects.
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