Effect of QSKL on MAPK and RhoA Pathways in a Rat Model of Heart Failure.
Effect of QSKL on MAPK and RhoA Pathways in a Rat Model of Heart Failure.
复制标题
QSKL 对心力衰竭大鼠模型 MAPK 和 RhoA 通路的影响
DOI：
10.1155/2017/3903898
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Xia K;Wang Q;Li C;Zeng Z;Wang Y;Wang W
芪参颗粒是治疗心力衰竭的中药方剂之一，具有抗纤维化作用。然而，其治疗作用的机制仍不清楚。在这项研究中，我们的目的是探讨QSKL是否可以发挥抗纤维化的作用，通过减弱ras同源家族成员A（RhoA）和丝裂原活化蛋白激酶（MAPK）途径。将大鼠随机分为假手术组、模型组、芪参康颗粒组和阳性对照组。结扎左心室前降支诱发心力衰竭。超声心动图测定心功能，Masson染色法测定胶原沉积。还测量了参与RhoA和MAPK通路的关键分子的表达。术后21 d，心功能严重受损，胶原沉积明显，而芪参康颗粒治疗可改善心功能，减轻胶原沉积。进一步的研究结果表明，这种作用可能是通过抑制细胞外信号调节激酶（ERK）和c-Jun N-末端激酶（JNK）的表达来介导的。与模型组相比，芪参康颗粒还能下调RhoA、Rho相关蛋白激酶1/2（ROCK 1/2）和磷酸化肌球蛋白轻链（p-MLC）的表达。QSKL对心力衰竭的保护机制可能是通过调节MAPK和RhoA信号通路来实现的。
Qishenkeli (QSKL) is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA) and mitogen activated protein kinase (MAPK) pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery. Cardiac functions were measured by echocardiography and collagen deposition was assessed by Masson staining. Expressions of the key molecules involved in the RhoA and MAPK pathways were also measured. Twenty-one days after surgery, cardiac functions were severely impaired and collagen deposition was remarkable, while QSKL treatment could improve heart functions and alleviate collagen deposition. Further results demonstrated that the effects may be mediated by suppressing expressions of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). Moreover, expressions of RhoA, Rho-associated protein kinase 1/2 (ROCK1/2), and phosphorylated myosin light chain (p-MLC) were also downregulated by QSKL compared with the model group. The cardioprotective mechanism of QSKL on heart failure is probably mediated by regulating both the MAPK and RhoA signaling pathways.