摘要
目的通过RhoA/ROCK1信号通路探讨抗纤益心方对扩张型心肌病(dilated cardiomyopathy,DCM)大鼠心肌纤维化的作用机制。方法将4周龄Wistar雄性大鼠100只随机选取10只作为正常组,其余90只通过呋喃唑酮诱导DCM大鼠模型,将造模成功大鼠随机分为模型组,抗纤益心方高(3.6 g·kg^(-1)·d^(-1))、中(1.8 g·kg^(-1)·d^(-1))、低剂量(0.9 g·kg^(-1)·d^(-1))及卡托普利组(10.125 mg·kg^(-1)·d^(-1))。连续给药4周后,超声检测大鼠心脏功能,HE、Masson检测心肌组织病理变化,Western blot、Real-time PCR检测心肌组织中Ras同源蛋白家族成员A(ras homologous family member A,RhoA)、Rho相关卷曲螺旋形成蛋白激酶1(rho associated coiled coil forming protein kinase 1,ROCK1)、肌球蛋白轻链(myosin light chain,MLC)、p-MLC、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、COI-I、结缔组织生长因子(connective tissue growth factor,CTGF)蛋白和mRNA表达水平。结果与正常组比较,模型组大鼠心脏功能明显降低(P<0.01),心肌组织结构异常、心肌纤维化明显,纤维化因子α-SMA、COI-1、CTGF的表达升高(P<0.01),RhoA/ROCK1信号通路表达上调(P<0.01);与模型组比较,抗纤益心方高、中剂量和卡托普利组大鼠心功能明显改善(P<0.05,P<0.01),心肌结构和心肌纤维化明显减轻,纤维化因子表达降低,RhoA/ROCK1信号通路表达下调(P<0.05,P<0.01);而低剂量组改善不明显(P>0.05)。结论抗纤益心方可以通过下调RhoA/ROCK1信号通路的来抑制扩张型心肌病大鼠心肌纤维化的发展。
Objective To explore the mechanism of Kangxian Yixin Decoction(抗纤益心方,KYD)on myocardial fibrosis in rats with dilated cardiomyopathy(DCM)through the Ras homologous family member A(RhoA)/Rho associated coiled coil form-ing protein kinase 1(ROCK1)signaling pathway.Methods A total of 100 Wistar male rats of 4 weeks old were randomly selected as the normal group,and the other 90 rats were injected furazolidone to induce the DCM models.The successfully modeled rats were randomly divided into model groups,KYD-high dose group(3.6 gkg^(-1)·d^(-1)),KYD-middle dose group(1.8 g·kg^(-1)·d^(-1)),KYD-low dose group(0.9g.kg^(-1)·d^(-1))and captopril group(10.125 mg.kg^(-1)·d^(-1)).Afer 4 weeks of con-tinuous administration,the heart function was detected by ultrasound,the pathological changes of myocardial tssue were detected by HE and Masson.Western blot and Real-time PCR were used to detect the expression levels of RhoA,ROCKI,myosin light chain(MLC),phosphorylated myosin(p-MLC),a-smooth muscle actin(a-SMA),COI-I,connective tissue growth factor(CTGF)protein and mRNA in myocardial tissue.Resuls Compared with those of the normal group,the heart function of the model group was significantly reduced(P<0.01),the myocardial tissue structure was abnormnal,myocardial fibrosis was obvious,and the expressions of a-SMA,COI-1 and CTGF increased(P<0.01).The expression of RhoA/R0CK1 signaling pathway was up - regulated(P <0. 01 ). Compared with those of the model group, the heart function of rats in the KYD - high dose group,KYD - middle dose group and the captopril group was signifcantly improved(P <0. 05,P<0.01). The myocardial structure and myocardial fibrosis were significantly reduced,the expressions of fibrotic factors decreased ,and the expression of RhoAV ROCKI signaling pathway was down - regulated(P<0.05,P<0. 01);while that of the KYD - low dose group was not significant(P>0.05). Conclusion KYD can inhibit the development of myocardial fibrosis in rats with DCM by down - regulating the RhoA/ ROCK1 signaling pathway.
作者
杨凤鸣
边汝涛
王冰
王振涛
吴鸿
YANG Fengming;BIAN Rutao;WANG Bing;WANG Zhentao;WU Hong(The Second Clinical Medical College of Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China;HenanUniversityof ChineseMedicine,Zhengzhou 450002,Henan,China)
出处
《中华中医药学刊》
CAS
北大核心
2022年第9期89-93,I0023,I0024,共7页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(81573920)
河南省中医药科学研究专项(2019JDZX003)
河南省中医院项目(2018YJKT07)。
