OBJECTIVE: Here, we evaluated the therapeutic effect of JDQYF on monocrotaline-induced right-sided heart failure associated with pulmonary arterial hypertension in Sprague-Dawley (SD) rats and investigated the potential mechanism of action.
METHODS: The main chemical components of JDQYF were detected and analyzed using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. The effects of JDQYF were investigated using a rat model of monocrotaline-induced right-sided heart failure associated with pulmonary arterial hypertension. We assessed the morphology of cardiac tissue using histopathology and the structure and function of the right heart using echocardiography. The biomarkers of heart failure, atrial natriuretic peptide and B-type natriuretic peptide, as well as serum pro-inflammatory markers, interleukin (IL)-1β, and IL-18, were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, the mRNA and protein expression levels of NLRP3 (NOD-, LRR-, and pyrin domain-containing 3), capase-1, IL-1β, and IL-18 in the right heart tissue were examined by real-time quantitative reverse transcription PCR and western blotting.
RESULTS: JDQYF improved ventricular function, alleviated pathological lesions in the right cardiac tissue, reduced the expression levels of biomarkers of heart failure and serum pro-inflammatory factors (IL-1β and IL-18), and downregulated the mRNA and protein expression levels of NLRP3, caspase-1, IL-1β, and IL-18 in the right cardiac tissue.
CONCLUSIONS: JDQYF possesses cardioprotective effect against right heart failure induced by pulmonary arterial hypertension, possibly owing to reduction of cardiac inflammation through the inhibition of NLRP3 inflammasome activation.
目标:这里,我们评价了JDQYF对野百合碱诱导的Sprague-Dawley(SD)大鼠肺动脉高压相关右心衰竭的治疗作用,并探讨了其潜在的作用机制.
方法:使用超高效液相色谱四极杆飞行时间质谱对JDQYF的主要化学成分进行检测和分析。使用野百合碱诱导的与肺动脉高压相关的右侧心力衰竭的大鼠模型研究了JDQYF的作用。我们使用组织病理学评估心脏组织的形态,并使用超声心动图评估右心的结构和功能。心力衰竭的生物标志物,心房利钠肽和B型利钠肽,以及血清促炎标志物,白细胞介素(IL)-1β,采用酶联免疫吸附试验(ELISA)检测IL-18。此外,NLRP3的mRNA和蛋白表达水平(NOD-,LRR-,和含pyrin结构域的3),capase-1,IL-1β,通过实时定量逆转录PCR和蛋白质印迹法检测右心组织中的IL-18。
结果:JDQYF改善了心室功能,减轻右侧心脏组织的病理损伤,降低心力衰竭标志物和血清促炎因子(IL-1β和IL-18)的表达水平,下调NLRP3、caspase-1、IL-1β的mRNA和蛋白表达水平,和右侧心脏组织中的IL-18。
结论:JDQYF对肺动脉高压引起的右心衰竭具有心脏保护作用,可能是由于通过抑制NLRP3炎性体激活来减少心脏炎症。