[关键词]
[摘要]
研究了原儿茶醛(Protocatechualdehyde,PCA)对糖尿病心肌病(Diabetic Cardiomyopathy,DCM)小鼠的心脏保护作用及其可能的分子机制。成功构建DCM小鼠模型后给予PCA干预治疗。记录小鼠心脏与体质量比值,测定心功能,检测心肌组织中促炎症因子、肌钙蛋白I、乳酸脱氢酶(Lactate Dehydrogenase,LDH)和肌酸激酶(Creatine Kinase,CK)的表达水平,并通过苏木精-伊红(Hematoxylin Eosin,HE)和马松染色观察了心肌组织的形态学变化。检测心肌组织和大鼠心肌细胞中核苷酸结合寡聚化结构域样受体蛋白3(Nod Like Receptor Protein 3,NLRP3)等蛋白的表达,并评估了PCA对心肌细胞存活率的影响。结果显示,PCA干预DCM小鼠中心脏与体质量比值、射血分数和短轴缩短距分别增加为5.42 mg/g、54.91%和28.07%,血清中LDH、CK和肌钙蛋白I分别降低为538.51 U/L、885.93 U/L和221.87 pg/mL,同时降低了肿瘤坏死因子α,白细胞介素1β和白细胞介素6的水平(P<0.05)。同时,PCA也能有效抑制高糖引起的心肌细胞毒性和NLRP3炎症小体的激活。PCA具有保护DCM小鼠心肌的作用,抑制NLRP3炎症小体的激活可能是发挥心脏改善作用的途径。
[Key word]
[Abstract]
The protective effects of protocatechualdehyde (PCA) on hearts of mice with diabetic cardiomyopathy (DCM) and its possible molecular mechanism were investigated. After the successful construction of DCM mouse models, PCA intervention was made. The heart-to-body mass ratio of mice and the cardiac function were determined. The expression levels of pro-inflammatory factors, troponin I, lactate dehydrogenase (LDH), and creatine kinase (CK) in the myocardial tissues were also determined. Hematoxylin and eosin (HE) staining and Masson staining methods were used to observe the morphological changes of the myocardial tissues. The expressions of nod-like receptor protein 3 (NLRP3) in the myocardial tissue and myocardial cells were detected, and the effects of PCA on the survival rate of myocardial cells were evaluated. The results showed that the heart-to-body mass ratio, ejection fraction, and fractional shortening increase by 5.42 mg/g, 54.91%, and 28.07%, respectively, after PCA intervention. At the same time, serum LDH, CK, and troponin I concentrations decrease to 538.51 U/L, 885.93 U/L, and 221.87 pg/mL, respectively. The levels of tumor necrosis factor-α, interleukin1β, and interleukin-6 also decreased (P<0.05). PCA also inhibited myocardial cytotoxicity and activation of NLRP3 inflammasome induced by high glucose concentrations. PCA can protect the myocardium of DCM mice. Inhibition of the activation of NLRP3 inflammasome may be the way to cardiac improvement.
[中图分类号]
[基金项目]
广东省普通高校药物早期毒性评价创新团队项目(2018KCXTD016)