Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction.
Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction.
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DOI：
10.1038/srep39551
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发表时间：
2016-12-21
影响因子：
4.6
通讯作者：
Connelly KA
中科院分区：
文献类型：
--
作者：
Bugyei-Twum A;Abadeh A;Thai K;Zhang Y;Mitchell M;Kabir G;Connelly KA
心脏纤维化是慢性肾脏病患者的常见发现。在这里，我们调查的心肾作用theracurmin，多酚化合物姜黄素的新配方，在慢性肾脏疾病的大鼠模型。简而言之，将Sprague-Dawley大鼠随机进行假手术或肾大部切除术（SNx）手术。在术后3周，SNx动物进一步随机化，通过每日一次经口管饲法接受theracurmin或溶剂，连续5周。术后8周，通过超声心动图和压力容积环分析评估心脏功能，然后收集LV和肾组织进行分析。SNx动物出现肾损伤的关键标志，包括高血压、蛋白尿、血尿素氮升高和肾小球硬化。SNx动物中的肾损伤还与显著的舒张功能障碍、巨噬细胞浸润和心脏NLRP 3炎性体活化相关。用theracurmin治疗SNx动物改善了与肾衰竭相关的心脏损伤的结构和功能表现，并且还减弱了心脏NLRP 3炎性小体活化和成熟IL-1β释放。综上所述，我们的研究结果表明，NLRP 3炎性小体在肾损伤诱导的心功能不全中具有重要作用，并将炎性小体衰减作为预防慢性肾脏疾病背景下不良心脏重塑的独特策略。
Cardiac fibrosis is a common finding in patients with chronic kidney disease. Here, we investigate the cardio-renal effects of theracurmin, a novel formulation of the polyphenolic compound curcumin, in a rat model of chronic kidney disease. Briefly, Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery. At 3 weeks post surgery, SNx animals were further randomized to received theracurmin via once daily oral gavage or vehicle for 5 consecutive weeks. At 8 weeks post surgery, cardiac function was assessed via echocardiography and pressure volume loop analysis, followed by LV and renal tissue collection for analysis. SNx animals developed key hallmarks of renal injury including hypertension, proteinuria, elevated blood urea nitrogen, and glomerulosclerosis. Renal injury in SNx animals was also associated with significant diastolic dysfunction, macrophage infiltration, and cardiac NLRP3 inflammasome activation. Treatment of SNx animals with theracurmin improved structural and functional manifestations of cardiac injury associated with renal failure and also attenuated cardiac NLRP3 inflammasome activation and mature IL-1β release. Taken together, our findings suggest a significant role for the NLRP3 inflammasome in renal injury-induced cardiac dysfunction and presents inflammasome attenuation as a unique strategy to prevent adverse cardiac remodeling in the setting of chronic kidney disease.
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影响因子：
10.8
作者：
Connelly, K. A.;Kelly, D. J.;Gilbert, R. E.
通讯作者：
Gilbert, R. E.
影响因子：
13.6
作者：
Parikh, CR;Abraham, E;Edelstein, CL
通讯作者：
Edelstein, CL
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
15.9
作者：
Melnikov, VY;Faubel, S;Edelstein, CL
通讯作者：
Edelstein, CL
DOI：
10.1152/ajpheart.00154.2010
发表时间：
2010-10-01
影响因子：
4.8
作者：
Ghosh, Siddhartha S.;Salloum, Fadi N.;Kukreja, Rakesh C.
通讯作者：
Kukreja, Rakesh C.