摘要
目的探讨和厚朴酚(Honokiol,HKL)对实验糖尿病动物和细胞模型心肌纤维化的影响及机制。方法培养大鼠心肌成纤维细胞,高糖、糖原合成酶激酶-3β(GSK-3β)作为诱导剂,观察HKL对纤维化相关蛋白的表达作用。通过小动物超声方法探究HKL在糖尿病引起的射血分数保留型心力衰竭(HFpEF)小鼠左心室收缩与舒张功能的影响;利用HE染色和Masson染色方法检测HKL对糖尿病小鼠心脏结构变化的影响。结果HKL能显著降低高糖诱导纤维化相关蛋白CollagenⅠ、CollagenⅢ、TGF-β、CTGF和FN的表达水平(P<0.05),并呈现剂量依赖性;HKL能显著降低GSK-3β诱导的纤维化相关蛋白表达水平(P<0.05)并显著降低GSK-3β和β-catenin的表达水平(P<0.05);HKL对心脏收缩功能射血分数(EF)和短轴缩短率(FS)无显著变化,对心脏舒张功能指标E/A比值显著降低(P<0.05),E峰下降时间(MVDT)与等容舒张时间(IVRT)明显延长(P<0.05);HKL对糖尿病心肌组织的结构损伤及胶原沉积有明显改善作用。结论HKL可通过下调GSK-3β、β-catenin抑制纤维化,从而改善糖尿病导致的心脏舒张功能不全。
Objective To investigate the protective effect and its mechanism of honokiol(HKL)on myocardial fibrosis in vitro and in vivo.Methods The effect of HKL on the expression of fibrosis related proteins of rat cardiac fibroblasts was observed with high glucose and GSK-3βas inducers.The effect of HKL on left ventricular systolic and diastolic function in diabetes-induced ejection fraction preserved heart failure(HFpEF)mice was investigated with echocardiography.HE staining and Masson trichrome staining were used to analyze the changes of myocardial tissue structure.Results HKL significantly decreased the expression of collagen I,collagen III,TGF-β,CTGF and FN in a dose-dependent manner(P<0.05).HKL also reduced the expression of GSK-3β-induced fibrosis related proteins and the expression of GSK-3βandβ-catenin(P<0.05).HKL had no significant influence on systolic function,including ejection fraction(EF)and fraction shortening(FS)and had obvious effects on diastolic function,including E/A ratio,mitral valve descending time(MVDT)and isovolumetric relaxation time(IVRT)(P<0.05).The structural damage and collagen deposition of diabetic myocardial tissue were significantly improved by HKL treatment.Conclusion HKL can inhibit fibrosis by down-regulating GSK-3βandβ-catenin,and improve diabetes-induced diastolic dysfunction.
作者
柯培雄
张许
岑怡
张贵平
张根水
KE Peixiong;ZHANG Xu;CEN Yi;ZHANG Guiping;ZHANG Genshui(Department of Pharmacology,Guangzhou Medical University,Guangzhou 511436,China)
出处
《广东药科大学学报》
CAS
2020年第5期651-656,共6页
Journal of Guangdong Pharmaceutical University
基金
广州市属高校科研计划项目(1201620072)。