中药基于TGF-β/Smad信号通路改善糖尿病心肌病的研究进展

Improvement of Diabetic Cardiomyopathy by Chinese Medicine Based on TGF-β/Smad Pathway:A Review

糖尿病心肌病(DCM)是糖尿病最常见的心血管病变之一。DCM的发生、发展与心肌纤维化密切相关,研究表明心肌纤维化是DCM重要的病理特征,因此针对心肌纤维化的治疗有助于延缓DCM的进程。在DCM进展的过程中,转化生长因子-β(TGF-β)/Smad信号通路的异常转导是高血糖诱导心肌纤维化的重要机制,TGF-β是心肌纤维化的关键因子,在DCM心肌纤维化过程中处于过度表达状态,Smad是TGF-β下游的主要效应因,TGF-β/Smad信号通过诱导心肌细胞凋亡,刺激肌成纤维细胞的过度产生,增加心肌细胞外基质(ECM)的沉积,在糖尿病心脏心肌纤维化的发病机制中发挥复杂作用。近年来中药在DCM的防治中发挥愈发重要的作用,基于TGF-β/Smad信号探寻中药干预DN进程的研究也逐渐增多。诸多药理研究表明,中药在防治DCM方面具备安全、高效等优势,具有明确的抑制心肌胶原沉积、抗心肌纤维化、改善心脏功能,保护心肌等功效,TGF-β/Smad信号通路是中药、中药单体和中药复方发挥DCM心肌保护作用的关键通路之一。鉴基于此,该篇将对近约10年以来中医药干预TGF-β/Smad信号通路治疗DCM现有的药理和实验研究成果进行综述,以期能为中药治疗DCM的进一步深入研究、开发和应用提供参考。

Diabetic cardiomyopathy(DCM)is one of the most common cardiovascular lesions in diabetes mellitus.The development and progression of DCM is closely related to myocardial fibrosis,which has been shown to be an important pathological feature of DCM.Therefore,the treatment targeting myocardial fibrosis can help slow down the DCM progress.In the DCM progress,abnormal transduction of transforming growth factor-β(TGF-β)/Smad signaling pathway is an important mechanism of hyperglycemia-induced myocardial fibrosis.TGF-βis a key factor of myocardial fibrosis and is overexpressed during myocardial fibrosis in DCM,and Smad is a major effector in the downstream of TGF-β.By inducing myocardial apoptosis,TGF-β/Smad signal stimulates the overproduction of myofibroblasts,increase the deposition of extracellular matrix(ECM),and plays a complex role in the pathogenesis of myocardial fibrosis in diabetic hearts.In recent years,Chinese medicine has played an increasingly important role in the prevention and treatment of DCM,and there has been an increase in the number of studies exploring the effects of Chinese medicine on the intervention of DN progress based on TGF-β/Smad signal.Various pharmacological studies have shown that Chinese medicine is safe and effective in the prevention and treatment of DCM,which has clear effects such as inhibiting the deposition of collagen,anti-myocardial fibrosis,improving cardiac function,and protecting myocardium,and TGF-β/Smad signaling pathway is one of the key pathways in which Chinese medicine,Chinese medicine monomers,and Chinese medicine compounds exert the myocardial protective effect in DCM.Based on this,this paper reviewed the existing pharmacological and experimental research results of Chinese medicine intervention in the TGF-β/Smad signaling pathway to treat DCM in the past decades,hoping to provide references for further in-depth research,development,and application of Chinese medicine in the treatment of DCM.