NLRP3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats.
NLRP3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats.
复制标题
NLRP3 炎症小体激活介导的细胞焦亡加重糖尿病大鼠心肌缺血/再灌注损伤
DOI：
10.1155/2017/9743280
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发表时间：
2017
影响因子：
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通讯作者：
Xia ZY
中科院分区：
文献类型：
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作者：
Qiu Z;Lei S;Zhao B;Wu Y;Su W;Liu M;Meng Q;Zhou B;Leng Y;Xia ZY
活性氧（ROS）诱导的NLRP 3炎性小体引发无菌炎症反应和焦亡，焦亡是由炎性半胱天冬酶激活引发的程序性细胞死亡的促炎形式。NLRP 3炎性体激活在心肌缺血/再灌注损伤中起重要作用。本研究探讨糖尿病是否通过NLRP 3炎性小体介导的细胞凋亡加重MI/R损伤。腹腔注射链脲佐菌素（60 mg/kg）建立1型糖尿病大鼠模型。结扎左前降支（LAD）30 min，再灌注2 h，建立MI/R模型。将H9 C2心肌细胞暴露于高葡萄糖（HG，30 mM）条件和缺氧/复氧（H/R）刺激。糖尿病大鼠心肌梗死面积、CK-MB和LDH释放均显著高于非糖尿病大鼠，并伴有NLRP 3炎性小体活化和细胞凋亡增加。用BAY 11 -7082抑制炎性小体活化显著降低MI/R损伤。体外研究显示，BAY 11 -7082或ROS清除剂N-乙酰半胱氨酸具有类似的作用，可减轻HG和H/R诱导的H9 C2细胞损伤。总之，高血压诱导的NLRP 3炎性小体激活可能是一个ROS依赖性的过程中pyroptotic细胞死亡，NLRP 3炎性小体诱导的pyroptosis加重MI/R损伤糖尿病大鼠。
The reactive oxygen species- (ROS-) induced nod-like receptor protein-3 (NLRP3) inflammasome triggers sterile inflammatory responses and pyroptosis, which is a proinflammatory form of programmed cell death initiated by the activation of inflammatory caspases. NLRP3 inflammasome activation plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Our present study investigated whether diabetes aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. Type 1 diabetic rat model was established by intraperitoneal injection of streptozotocin (60 mg/kg). MI/R was induced by ligating the left anterior descending artery (LAD) for 30 minutes followed by 2 h reperfusion. H9C2 cardiomyocytes were exposed to high glucose (HG, 30 mM) conditions and hypoxia/reoxygenation (H/R) stimulation. The myocardial infarct size, CK-MB, and LDH release in the diabetic rats subjected to MI/R were significantly higher than those in the nondiabetic rats, accompanied with increased NLRP3 inflammasome activation and increased pyroptosis. Inhibition of inflammasome activation with BAY11-7082 significantly decreased the MI/R injury. In vitro studies showed similar effects, as BAY11-7082 or the ROS scavenger N-acetylcysteine, attenuated HG and H/R-induced H9C2 cell injury. In conclusion, hyperglycaemia-induced NLRP3 inflammasome activation may be a ROS-dependent process in pyroptotic cell death, and NLRP3 inflammasome-induced pyroptosis aggravates MI/R injury in diabetic rats.
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影响因子：
9.3
作者：
Ding M;Lei J;Han H;Li W;Qu Y;Fu E;Fu F;Wang X
通讯作者：
Wang X
影响因子：
4
作者：
Harijith A;Ebenezer DL;Natarajan V
通讯作者：
Natarajan V
影响因子：
37.8
作者：
Arslan, Fatih;Smeets, Mirjam B.;de Kleijn, Dominique P. V.
通讯作者：
de Kleijn, Dominique P. V.
缺血和再灌注 - 从翻译机构。
影响因子：
82.9
作者：
通讯作者：
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影响因子：
64.8
作者：
通讯作者：
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