Ranolazine Inhibits Pyroptosis via Regulation of miR-135b in the Treatment of Diabetic Cardiac Fibrosis.
Ranolazine Inhibits Pyroptosis via Regulation of miR-135b in the Treatment of Diabetic Cardiac Fibrosis.
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雷诺嗪通过调节 miR-135b 抑制细胞焦亡治疗糖尿病心脏纤维化
DOI：
10.3389/fmolb.2022.806966
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发表时间：
2022
影响因子：
5
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
Ren L;Chen X;Nie B;Qu H;Ju J;Bai Y
糖尿病心肌病（DCM）是糖尿病（DM）的主要心血管并发症，心肌纤维化是DCM的特征性病理表现。DCM可因焦亡而加重，焦亡是microRNA（miRNAs）的潜在靶点。miR-135 b参与延缓许多心血管疾病的进展，然而，miR-135 b在糖尿病心脏纤维化中的作用尚不清楚。雷诺嗪是一种哌嗪衍生物，可有效治疗心血管疾病。本研究的目的是阐明雷诺嗪抗糖尿病心脏纤维化的作用机制，并研究miR-135 b在此过程中的作用。用超声心动图、苏木精-伊红（H&E）染色和Masson染色观察大鼠心脏功能和结构的变化。采用免疫组化法检测大鼠左心室内caspase-1、白细胞介素-1 β（IL-1β）、Gasdermin D（GSDMD）、转化生长因子-β1（TGF-β1）、I型胶原和III型胶原的表达。采用免疫印迹法和免疫荧光法检测caspase-1、IL-1β、GSDMD、TGF-β1、I型胶原和III型胶原蛋白的蛋白表达，采用荧光定量PCR法检测mRNA水平。雷诺嗪减少了大鼠的焦亡，抑制了胶原沉积，改善了心脏功能。雷诺嗪增加了高糖处理的心脏成纤维细胞中miR-135 b的表达，miR-135 b直接与caspase-1结合。干扰miR-135 b降低雷诺嗪对焦亡和胶原沉积的影响。雷诺嗪治疗糖尿病心脏纤维化通过上调miR-135 b抑制焦亡和胶原沉积。本研究为深入了解糖尿病心肌纤维化的发病机制及雷诺嗪治疗DCM的临床应用提供了坚实的理论基础。
Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus (DM), and cardiac fibrosis is a characteristic pathological manifestation of DCM. DCM can be exacerbated by pyroptosis, and pyroptosis is a potential target of microRNAs (miRNAs). miR-135b is involved in delaying the progression of numerous cardiovascular diseases, Nonetheless, the role of miR-135b in diabetic cardiac fibrosis is unclear. Ranolazine is a piperazine derivative and is effective for the treatment of cardiovascular disease. The purpose of the study was to elucidate the mechanism of action of ranolazine against diabetic cardiac fibrosis and to investigate the role of miR-135b in this process. Functional and structural changes in the rat heart were examined by echocardiography, hematoxylin-eosin (H&E) and Masson staining. Immunohistochemistry was used to assess the expression of caspase-1, interleukin-1β (IL-1β), gasdermin D (GSDMD), transforming growth factor-β1 (TGF-β1), collagen I and collagen III in the rat left ventricle. Western blot and immunofluorescence were used to detect the protein expression of caspase-1, IL-1β, GSDMD, TGF-β1, collagen I and collagen III proteins, and the mRNA levels were determined using fluorescent quantitative PCR. Ranolazine reduced pyroptosis and inhibited collagen deposition, improving cardiac function in rats. Ranolazine increased miR-135b expression in high glucose-treated cardiac fibroblasts, and miR-135b directly bound to caspase-1. Interference with miR-135b reduced the effects of ranolazine on pyroptosis and collagen deposition. Ranolazine treatment of diabetic cardiac fibrosis inhibited pyroptosis and collagen deposition by upregulating miR-135b. Our study provides a solid theoretical basis for understanding the pathogenesis of diabetic cardiac fibrosis and the clinical use of ranolazine in the treatment of DCM.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
影响因子：
4.9
作者：
de Simone G;Devereux RB;Chinali M;Lee ET;Galloway JM;Barac A;Panza JA;Howard BV
通讯作者：
Howard BV
影响因子：
5.6
作者：
Hölscher ME;Bode C;Bugger H
通讯作者：
Bugger H
影响因子：
16.2
作者：
Chisholm JW;Goldfine AB;Dhalla AK;Braunwald E;Morrow DA;Karwatowska-Prokopczuk E;Belardinelli L
通讯作者：
Belardinelli L
影响因子：
39.3
作者：
Palomer, Xavier;Silvia Roman-Azcona, M.;Vazquez-Carrera, Manuel
通讯作者：
Vazquez-Carrera, Manuel