ISO-alpha-acids improve the hematoma resolution and prevent peri-hematoma inflammations by transforming microglia via PPARgamma-CD36 axis in ICH rats
ISO-alpha-acids improve the hematoma resolution and prevent peri-hematoma inflammations by transforming microglia via PPARgamma-CD36 axis in ICH rats
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ISO-α-酸通过 PPARgamma-CD36 轴转化 ICH 大鼠的小胶质细胞，改善血肿消退并预防血肿周围炎症
DOI：
10.1016/j.intimp.2020.106396
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发表时间：
2020
影响因子：
5.6
通讯作者：
Rong Xie
中科院分区：
文献类型：
--
作者：
Jian-Lan Zhao;Yan-Jie Chen;Jian Yu;Zhuo-Ying Du;Qiang Yuan;Yi-Rui Sun;Xing Wu;Zhi-Qi Li;Xue-Hai Wu;Jin Hu;Rong Xie
目的探讨PPAR-γ激动剂ISO-α-酸（IAAs）对脑出血大鼠的作用及其可能机制。材料与方法采用100 μl自体动脉血立体定向注射诱导大鼠脑出血模型。90只雄性大鼠随机分为5组：自体血和IAAs (IAA)；给予自体血、IAAs和PPAR-γ抑制剂（IAA + GW9662）；自体血和生理盐水（生理盐水）；只有自体血（Mock）；只注射针（Sham）。采用mNSS评估神经功能。检测血肿体积、脑含水量、表面蛋白及炎症因子。小胶质细胞的抗炎能力也被评估。结果与生理盐水、模拟盐水相比，aas能显著降低脑出血大鼠的mNSS评分，减轻脑含水量，改善血肿消退（p < 0.05）。IAAs可诱导更多的“M2”小胶质/巨噬细胞。IAA组cd36表达量显著高于其他各组（p < 0.05）。注射IAAs可显著增加cd11b和cd206双阳性抗炎型小胶质/巨噬细胞，降低炎症因子表达（p < 0.05）。GW9662可以缓解这种保护作用。结论本研究首次阐明了IAAs与ICH之间的关系。IAAs能够加速血肿吸收，减轻脑水肿，抑制血肿周围炎症，最终改善脑出血大鼠的预后。该表型是由于IAAs通过激活PPAR-γ和增加cd36表达诱导“M2”小胶质细胞/巨噬细胞。
ObjectiveTo elucidate the effects of ISO-α-acids (IAAs), a PPAR-γ agonist, on ICH rats and its potential mechanism.Material and methodsThe Sprague Dawley rats ICH model was induced by stereotactic injecting of 100 μl autologous artery blood. Ninety male rats were randomly allocated to five groups: autologous blood and IAAs (IAA); received autologous blood, IAAs and PPAR-γ inhibitor (IAA + GW9662); autologous blood and normal Saline (Saline); only autologous blood (Mock); and only needle injection (Sham). Neurological functions were assessed by mNSS. Hematoma volume, brain water content, surface proteins and inflammatory factors were detected. The microglia anti-inflammatory abilities were also evaluated.ResultsIAAs were able to significantly decrease ICH rat’s mNSS scores, alleviate brain water content, improve hematoma resolution than Saline, Mock (p < 0.05). More “M2” microglial/macrophage can be induced by IAAs. The expression of CD 36 was statistically higher in IAA than other groups (p < 0.05). Injection of IAAs led to a greatly increasing in CD 11b and CD 206 double-positive anti-inflammatory type microglial/macrophage, moreover, a reduction of inflammatory cytokines expression (p < 0.05). Such protective effects can be relieved by GW9662.ConclusionsThis is the first study to elucidate the relationship between IAAs and ICH. IAAs were able to accelerate hematoma absorption, alleviate brain edema, suppress peri-hematoma inflammations and finally improved the outcome of ICH rats. The phenotype was due to the IAAs induction of “M2” microglial/macrophage via activating of PPAR-γ and increasing CD 36 expression.