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目的:研究缬沙坦对心力衰竭(HF)时肌浆网(SR)钙离子调节蛋白的保护作用。方法:采用腹主动脉-下腔静脉造瘘术建立幼鼠HF模型,术后8周随机分为2组:未治疗组和治疗组(管饲缬沙坦),另设假手术组。对各组幼鼠左室组织提取SR膜,Western blotting法测定受磷蛋白(PLB)磷酸化水平,荧光分光光度仪检测钙离子(Ca2+)的重吸收和渗漏。结果:与假手术组比较,未治疗组体重降低(P<0.01),左室相对质量(LVRW)、右室相对质量(RVRW)均明显升高(P<0.01),16位丝氨酸磷酸化-受磷蛋白(Ser-16-PLB)蛋白量显著降低(P<0.01);与未治疗组比较,治疗组体重(P<0.01)升高,LVRW、RVRW降低(P<0.01),Ser-16-PLB蛋白量明显升高(P<0.01),接近假手术组水平;3组总PLB蛋白量差异无统计学意义(P>0.05);若分别向含有3组SR的缓冲液加入ATP(0.5mmol/L)后,未治疗组的Ca2+的重吸收量同假手术组和治疗组比较,明显降低(P<0.01);当分别向含有3组SR的缓冲液中加入毒胡萝卜内酯(1μmol/L)后,未治疗组同另外2组比较出现明显的Ca2+渗漏(P<0.01);而当毒胡萝卜内酯(1μmol/L)和FKBP抑制剂FK506(30μmol/L)一起加入3组SR的缓冲液中,假手术组、治疗组出现明显的Ca2+渗漏(P<0.01),而未治疗组较单独加入毒胡萝卜内酯时Ca2+渗漏仅轻微增多(P>0.05)。结论:HF时心肌组织肥厚,细胞Ca2+重吸收量降低、渗漏明显,心肌PLB磷酸化水平显著降低。缬沙坦一方面抑制Ca2+渗漏,另一方面提高PLB的磷酸化水平,恢复Ca2+-ATP酶的Ca2+重吸收能力,提高心脏功能并有效抑制心室重塑。
AIM: To investigate the protective effect of valsartan on sarcoplasmic reticulum (SR) calcium-regulated protein in heart failure (HF). Methods: The HF model was established by abdominal aorta - inferior vena cava fistula. The rats were randomly divided into two groups at 8 weeks after operation: untreated group and treatment group (valsartan tube feeding), and another sham operation group. SR membranes were extracted from left ventricular tissues of young rats in each group. Phosphorylation of phospholamban (PLB) was measured by Western blotting and reabsorption and leakage of calcium (Ca2 +) by fluorescence spectrophotometer. Results: Compared with the sham - operated group, the body weight of the untreated group was significantly lower (P <0.01), LVRW and RVRW were significantly increased (P <0.01) Compared with the untreated group, the body weight (P <0.01), LVRW and RVRW decreased (P <0.01) and Ser-16 (P <0.01), which was close to the level of sham-operation group. There was no significant difference in the total PLB protein in the three groups (P> 0.05) mmol / L), the reabsorption of Ca2 + in the untreated group was significantly lower than that in the sham-operated and untreated groups (P <0.01). When the concentration of Ca (superscript 2+) (P <0.01). When Ca (superscript 2 +) L (1μmol / L) and FK506 (30μmol / L) were added to the three groups In Ca2 + SR SR group, Ca2 + leakage was significantly increased in sham-operation group and treatment group (P <0.01), while Ca2 + leakage in untreated group increased only slightly (P> 0.05). Conclusion: Hypertrophy of myocardium in HF group decreased cellular reabsorption of Ca2 +, markedly infiltrated and significantly decreased phosphorylation of PLB in myocardium. Valsartan can inhibit the leakage of Ca2 + on the one hand and increase the phosphorylation of PLB on the other hand, restore the Ca2 + reabsorption capacity of Ca2 + -ATPase, improve cardiac function and effectively inhibit ventricular remodeling.