Chronic Low-Dose Alcohol Consumption Attenuates Post-Ischemic Inflammation via PPARγ in Mice.
Chronic Low-Dose Alcohol Consumption Attenuates Post-Ischemic Inflammation via PPARγ in Mice.
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DOI：
10.3390/ijms22105121
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发表时间：
2021-05-12
影响因子：
5.6
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Li C;Li J;Loreno EG;Miriyala S;Panchatcharam M;Lu X;Sun H
缺血性中风是成人死亡和永久残疾的主要原因之一。近年来，我们发现少量饮酒可抑制缺血后炎症反应，而炎症反应在缺血性脑损伤中起重要作用。我们的目的是确定过氧化物酶体增殖物激活受体-γ（PPARγ）在LAC抗短暂性局灶性脑缺血的抗炎作用中的作用。在体内研究中，雄性C57 BL/6 J野生型（WT）和内皮特异性条件性PPARγ敲除小鼠每天灌胃0.7 g/kg/天乙醇或体积匹配的水，持续8周。从第7周开始，腹腔注射3 mg/kg/天GW 9662（选择性PPARγ拮抗剂），持续两周。在单侧大脑中动脉闭塞（MCAO）90 min/再灌注24 h之前和之后，评价脑缺血/再灌注（I/R）损伤和大脑皮质锰超氧化物歧化酶（MnSOD）和粘附分子的表达、中性粒细胞浸润和小胶质细胞活化。在体外实验中，观察慢性酒精暴露对C57 BL/6 J小鼠脑微血管内皮细胞（MBMVECs）过氧化物酶体增殖物激活受体γ（PPARγ）和锰超氧化物歧化酶（MnSOD）表达的影响。在酒精喂养的WT小鼠和低浓度酒精暴露的C57 BL/6 J MBMVECs的大脑皮层中，PPARγ和MnSOD显著上调。GW 9662显著抑制酒精诱导的MnSOD上调。8周乙醇喂养显著减少脑I/R损伤，减轻缺血后炎症反应（上调细胞间粘附分子-1（ICAM-1）和E-选择素，小胶质细胞活化和中性粒细胞浸润）。GW 9662和内皮特异性条件性敲除PPARγ治疗未改变对照小鼠的脑I/R损伤和炎症反应，但消除了乙醇喂养小鼠的神经保护作用。此外，GW 9662和内皮特异性条件性敲除PPARγ可减弱LAC对缺血后粘附分子表达和中性粒细胞浸润的抑制作用。本研究结果提示LAC可能通过激活PPARγ抑制缺血后炎症反应而对脑I/R损伤起到保护作用。
Ischemic stroke is one of the leading causes of death and permanent disability in adults. Recently, we found that light alcohol consumption (LAC) suppresses post-ischemic inflammatory response, which plays an important role in ischemic brain damage. Our goal was to determine the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in the anti-inflammatory effect of LAC against transient focal cerebral ischemia. In in vivo study, male C57BL/6J wild type (WT) and endothelial-specific conditional PPARγ knockout mice were gavage fed with 0.7 g/kg/day ethanol or volume-matched water daily for 8 weeks. From the 7th week, 3 mg/kg/day GW9662 (a selective PPARγ antagonist) was intraperitoneally given for two weeks. Cerebral ischemia/reperfusion (I/R) injury and expression of manganese superoxide dismutase (MnSOD) and adhesion molecules, neutrophil infiltration, and microglial activation in the cerebral cortex before and following a 90 min unilateral middle cerebral artery occlusion (MCAO)/24 h reperfusion were evaluated. In in vitro study, the impact of chronic alcohol exposure on expression of PPARγ and MnSOD in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs) was measured. PPARγ and MnSOD were significantly upregulated in the cerebral cortex of ethanol-fed WT mice and low-concentration ethanol-exposed C57BL/6J MBMVECs. GW9662 significantly inhibited alcohol-induced upregulation of MnSOD. Eight-week ethanol feeding significantly reduced cerebral I/R injury and alleviated the post-ischemic inflammatory response (upregulation of intercellular adhesion molecule-1 (ICAM-1) and E-selectin, microglial activation, and neutrophil infiltration). Treatment with GW9662 and endothelial-specific conditional knockout of PPARγ did not alter cerebral I/R injury and the inflammatory response in the control mice but abolish the neuroprotective effect in ethanol-fed mice. In addition, GW9662 and endothelial-specific conditional knockout of PPARγ diminished the inhibitory effect of LAC on the post-ischemic expression of adhesion molecules and neutrophil infiltration. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing the post-ischemic inflammation via activation of PPARγ.
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影响因子：
3.4
作者：
Jin, Rong;Liu, Lin;Zhang, Shihao;Nanda, Anil;Li, Guohong
通讯作者：
Li, Guohong
DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
通讯作者：
Korthuis, Ronald J.
DOI：
10.1186/2046-2395-3-6
发表时间：
2014
期刊：
Longevity & healthspan
影响因子：
--
作者：
Dai DF;Chiao YA;Marcinek DJ;Szeto HH;Rabinovitch PS
通讯作者：
Rabinovitch PS
影响因子：
4.2
作者：
Chavez, Pollyanna R. G.;Lian, Fuzhi;Wang, Xiang-Dong
通讯作者：
Wang, Xiang-Dong
影响因子：
6.3
作者：
Justicia, C;Martín, A;Planas, AM
通讯作者：
Planas, AM