抗纤益心方对扩张型心肌病大鼠心肌细胞CaN/NFAT3信号转导通路的影响

Effects of Kangxian Yixin Formula on CaN/NFAT3 signal transduction pathway of cardiomyocyte in rats with dilated cardiomyopathy

目的:探讨抗纤益心方对扩张型心肌病(DCM)大鼠心肌细胞CaN/NFAT3信号转导通路的影响。方法:通过饮用呋喃唑酮水溶液诱导DCM大鼠模型,造模10周后将造模成功的大鼠随机分为模型组,抗纤益心方高、低剂量组和卡托普利组,另设正常组。药物干预4周后超声心动图检查各组大鼠心功能,HE染色及电镜观察心肌组织病理学变化;比色法检测心肌组织中CaN含量,ELISA法检测血清中血管紧张素Ⅱ(AngⅡ)含量,Western Blot检测心肌组织中NAFT3蛋白表达情况,Real-time PCR法检测心肌组织中ANP、BNP、NAFT3 mRNA表达水平。结果:与正常组比较,模型组大鼠心功能显著降低(P<0.01),心肌细胞病理损伤明显,心肌组织中CaN活性及血清中AngⅡ含量显著增加(P<0.01),心肌组织中ANP、BNP、NAFT3 mRNA表达量显著升高(P<0.01);与模型组比较,各药物干预组均可以显著改善心功能(P<0.05,P<0.01),减轻心肌细胞病理损伤,降低心肌组织中CaN活性及血清中AngⅡ含量,降低ANP、BNP、NAFT3 mRNA表达水平(P<0.01,P<0.05),但抗纤益心方低剂量降低血清中AngⅡ含量差异无统计学意义。结论:抗纤益心方可以改善DCM模型大鼠心功能,减轻心肌组织病理损伤,抑制心肌细胞肥大,可能与调节Ca N/NFAT3信号转导通路有关。

Objective: To investigate the effect of Kangxian Yixin Formula on the CaN/NFAT3 signal transduction pathway in cardiomyocytes of rats with dilated cardiomyopathy(DCM). Methods: The DCM rat model was induced by drinking furazolidone aqueous solution. After 10 weeks of modeling, the successfully established rats were randomly divided into the model group, the high-dose and low-dose groups of Kangxian Yixin Formula, and the captopril group. After 4 weeks of drug intervention, the cardiac function of the rats in each group was examined by echocardiography, and the pathological changes of myocardial tissue were observed by HE staining and electron microscope;the content of CaN in myocardial tissue was detected by colorimetry, and the content of angiotensin II(Ang II) in serum was detected by ELISA, Western Blot was used to detect the expression of NAFT3 protein in myocardial tissue, and Real-time PCR method was used to detect the expression levels of ANP, BNP and NAFT3 in myocardial tissue. Results: Compared with the normal group, the cardiac function of the rats in the model group was significantly reduced(P<0.01), the myocardial cell pathological damage was obvious, the CaN activity in the myocardial tissue and the content of Ang II in the serum were significantly increased(P<0.01), and the ANP, BNP and NAFT3 mRNA in the myocardial tissue expressions were significantly increased(P<0.01);Compared with the model group, each drug intervention group could significantly improve cardiac function(P<0.05, P<0.01),relieve myocardial cell pathological damage, and reduce myocardial tissue damage, the activity of CaN and the content of Ang I in serum decreased the mRNA expression levels of ANP, BNP and NAFT3(P<0.01, P<0.05), while the low-dose Kangxian Yixin Formula decreased the content of Ang Ⅱ in serum without statistical significance. Conclusion: Kangxian Yixin Formula can improve cardiac function in DCM model rats, reduce myocardial tissue pathological damage, and inhibit myocardial cell hypertrophy, which may be related to the regulation of CaN/NFAT3 signal transduction pathway.