扩张型心肌病相关信号通路及其中医药调控研究进展

Signaling Pathways Related to Dilated Cardiomyopathy and Their Regulation by Traditional Chinese Medicine:A Review

扩张型心肌病(DCM)主要病理改变为左心室扩大为主的全心扩大,临床表现为心功能下降、心律失常、血栓栓塞等,甚者可能发生猝死,是难治性心血管疾病之一。临床仍以保守药物治疗为主,但因其无法规避的血压过低等不良反应常难以达到满意预后,而中西医结合治疗可有效改善副作用、提高疗效。研究发现,核转录因子-κB(NF-κB)、腺苷酸活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)、转化生长因子-β(TGF-β)/Smads、Toll样受体(TLR)4/c-Jun氨基末端激酶(JNK)丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶(Akt)等信号通路在DCM的发生发展中起到了关键的调控作用,且中医方药可通过调控上述信号通路起到改善心肌纤维化、逆转心室重构、减轻氧化应激、抗炎等多种作用改善DCM,并且因其多靶点、多机制的作用特点具有安全性高、耐受性良好的优势,已经成为当前临床治疗的重要内容。

Dilated cardiomyopathy(DCM)is characterized by the main pathological changes of global cardiac enlargement,especially left ventricular enlargement.Clinical manifestations include decreased heart function,arrhythmia,thromboembolism,and even sudden death.It is one of the refractory cardiovascular diseases.Conservative drug treatment is still the main approach in clinical practice,but due to its unavoidable side effects such as low blood pressure,it is often difficult to achieve a satisfactory prognosis.The combination of traditional Chinese medicine and Western medicine can effectively improve side effects and enhance efficacy.The research has found that nuclear transcription factors-κB(NF-κB),adenylate activated protein kinase(AMPK)/mammalian rapamycin target protein(mTOR),transforming growth factor-β(TGF-β)/Smads,Toll like receptors(TLR)4/c-Jun amino terminal kinase(JNK),mitogen activated protein kinase(MAPK),phosphatidylinositol 3-kinase(PI3K)/protein kinase(Akt),and other signaling pathways play a crucial regulatory role in the occurrence and development of DCM.Traditional Chinese medicine can improve myocardial fibrosis,reverse ventricular remodeling,alleviate oxidative stress,and achieve anti-inflammatory and other effects by regulating the above signaling pathways,thus improving DCM.Due to its multi-target and multi-mechanism characteristics,it has the advantages of high safety and good tolerance and has become an important part of current clinical treatment.