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白藜芦醇可预防软脂酸诱导的心肌细胞收缩功能障碍。

Resveratrol prevents palmitic-acid-induced cardiomyocyte contractile impairment.

机构信息

Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.

Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.

出版信息

Can J Physiol Pharmacol. 2019 Dec;97(12):1132-1140. doi: 10.1139/cjpp-2019-0051. Epub 2019 Aug 2.

Abstract

Long-chain saturated fatty acids, especially palmitic acid (PA), contribute to cardiomyocyte lipotoxicity. This study tests the effects of PA on adult rat cardiomyocyte contractile function and proteins associated with calcium regulating cardiomyocyte contraction and relaxation. Adult rat cardiomyocytes were pretreated with resveratrol (Resv) and then treated with PA. For the reversal study, cardiomyocytes were incubated with PA prior to treatment with Resv. Cardiomyocyte contractility, ratio of rod- to round-shaped cardiomyocytes, and Hoechst staining were used to measure functional and morphological changes in cardiomyocytes. Protein expression of sarco-endoplasmic reticulum ATPase 2a (SERCA2a), native phospholamban (PLB) and phosphorylated PLB (pPLB ser16 and pPLB thr17), and troponin I (TnI) and phosphorylated TnI (pTnI) were measured. SERCA2a activity was also measured. Our results show that PA (200 μM) decreased the rate of cardiomyocyte relaxation, reduced the number of rod-shaped cardiomyocytes, and increased the number of cells with condensed nuclei; pre-treating cardiomyocytes with Resv significantly prevented these changes. Post-treatment with Resv did not reverse morphological changes induced by PA. Protein expression levels of SERCA2a, PLB, pPLBs, TnI, and pTnI were unchanged by PA or Resv. SERCA2a activity assay showed that and Iono ratio were increased with PA and pre-treatment with Resv prevented this increase. In conclusion, our results show that Resv protect cardiomyocytes from contractile dysfunction induced by PA.

摘要

长链饱和脂肪酸,尤其是棕榈酸(PA),会导致心肌细胞脂肪毒性。本研究检测了 PA 对成年大鼠心肌细胞收缩功能和与钙调节心肌细胞收缩和舒张相关的蛋白的影响。成年大鼠心肌细胞先用白藜芦醇(Resv)预处理,然后用 PA 处理。对于逆转研究,心肌细胞先用 PA 孵育,然后用 Resv 处理。用心肌细胞收缩性、杆状-圆形心肌细胞的比例和 Hoechst 染色来测量心肌细胞的功能和形态变化。肌浆网-内质网 ATP 酶 2a(SERCA2a)、天然磷蛋白(PLB)和磷酸化 PLB(pPLB ser16 和 pPLB thr17)、肌钙蛋白 I(TnI)和磷酸化 TnI(pTnI)的蛋白表达水平也进行了测量。还测量了 SERCA2a 活性。我们的结果表明,PA(200μM)降低了心肌细胞舒张的速度,减少了杆状心肌细胞的数量,增加了核浓缩细胞的数量;Resv 预处理显著预防了这些变化。PA 诱导的形态变化用 Resv 后处理不能逆转。PA 或 Resv 对 SERCA2a、PLB、pPLBs、TnI 和 pTnI 的蛋白表达水平没有影响。SERCA2a 活性测定表明,PA 增加了 Iono 比值,Resv 预处理可预防这种增加。总之,我们的结果表明,Resv 可保护心肌细胞免受 PA 诱导的收缩功能障碍。

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