PPAR-γ Activation Prevents Septic Cardiac Dysfunction via Inhibition of Apoptosis and Necroptosis.
PPAR-γ Activation Prevents Septic Cardiac Dysfunction via Inhibition of Apoptosis and Necroptosis.
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PPAR-gamma 激活通过抑制细胞凋亡和坏死性凋亡来预防脓毒性心脏功能障碍
DOI：
10.1155/2017/8326749
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发表时间：
2017
影响因子：
--
通讯作者：
Xiao F
中科院分区：
文献类型：
--
作者：
Peng S;Xu J;Ruan W;Li S;Xiao F
脓毒症引起的心脏功能障碍仍然是重症监护病房死亡的主要原因之一。过度的炎症反应和不受限制的细胞死亡在脓毒症引起的心脏功能障碍中发挥着关键作用。过氧化物酶体增殖物激活受体（PPAR-）γ 已被证明对脓毒症具有心脏保护作用。然而，PPAR-γ介导的心脏保护机制及其与炎症和细胞死亡的关系尚不清楚。我们假设通过减少心脏炎症、心肌细胞凋亡和坏死性凋亡来激活 PPAR-γ 可以预防脓毒症时的心肌功能障碍。在有或没有PPAR-γ激动剂（罗格列酮）或拮抗剂T0070907（T007）的情况下对大鼠进行盲肠结扎和穿刺（CLP）。 CLP后，心功能显着下降，这与心肌受损、促炎细胞因子上调以及细胞凋亡、坏死和坏死性凋亡增加有关。这一过程与抑制剂 κB (IκBα) 的减少和 NF-κB、受体相互作用蛋白激酶 1 (RIP1)、RIP3 和混合谱系激酶样 (MLKL) 蛋白的增加相对应。罗格列酮预处理激活 PPAR-γ 可增强 PPAR-γ 活性并阻止这些变化，从而提高脓毒症大鼠的存活率。相比之下，T007对PPAR-γ的抑制进一步加剧了病情，使存活率降至接近0%。总之，PPAR-γ 激活通过减少心肌中的促炎细胞因子、细胞凋亡和坏死性凋亡来预防脓毒症心肌功能障碍。
Sepsis-induced cardiac dysfunction remains one of the major causes of death in intensive care units. Overwhelmed inflammatory response and unrestrained cell death play critical roles in sepsis-induced cardiac dysfunction. Peroxisome proliferator-activated receptor- (PPAR-) γ has been proven to be cardioprotective in sepsis. However, the mechanism of PPAR-γ-mediated cardioprotection and its relationship with inflammation and cell death are unclear. We hypothesized that activation of PPAR-γ by reducing cardiac inflammation, myocardial apoptosis, and necroptosis may prevent myocardial dysfunction in sepsis. Rats were subjected to cecal ligation and puncture (CLP) with or without PPAR-γ agonist (rosiglitazone) or antagonist T0070907 (T007). After CLP, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated proinflammatory cytokines, and increased apoptosis, necrosis, and necroptosis. This process is corresponded with decreased inhibitor κB (IκBα) and increased NF-κB, receptor-interacting protein kinase-1 (RIP1), RIP3, and mixed lineage kinase-like (MLKL) protein. Activation of PPAR-γ by rosiglitazone pretreatment enhanced PPAR-γ activity and prevented these changes, thereby improving the survival of septic rats. In contrast, inhibition of PPAR-γ by T007 further exacerbated the condition, dropping the survival rate to nearly 0%. In conclusion, PPAR-γ activation by reducing proinflammatory cytokines, apoptosis, and necroptosis in the myocardium prevents septic myocardial dysfunction.
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DOI：
10.1097/shk.0000000000000520
发表时间：
2016-04
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Araújo CV;Campbell C;Gonçalves-de-Albuquerque CF;Molinaro R;Cody MJ;Yost CC;Bozza PT;Zimmerman GA;Weyrich AS;Castro-Faria-Neto HC;Silva AR
通讯作者：
Silva AR
影响因子：
30.3
作者：
Nogusa S;Thapa RJ;Dillon CP;Liedmann S;Oguin TH 3rd;Ingram JP;Rodriguez DA;Kosoff R;Sharma S;Sturm O;Verbist K;Gough PJ;Bertin J;Hartmann BM;Sealfon SC;Kaiser WJ;Mocarski ES;López CB;Thomas PG;Oberst A;Green DR;Balachandran S
通讯作者：
Balachandran S
影响因子：
3.2
作者：
Kaplan J;Nowell M;Chima R;Zingarelli B
通讯作者：
Zingarelli B
影响因子：
3.7
作者：
Furian, Thiago;Aguiar, Cyntia;Biolo, Andreia
通讯作者：
Biolo, Andreia
DOI：
10.1161/circheartfailure.112.000177
发表时间：
2013-05
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Drosatos K;Khan RS;Trent CM;Jiang H;Son NH;Blaner WS;Homma S;Schulze PC;Goldberg IJ
通讯作者：
Goldberg IJ