脱氢表雄酮对缺血性心力衰竭大鼠心房颤动的保护作用

Protective Effect of Dehydroepiandrosterone on Atrial Fibrillation in Rats with Ischemic Heart Failure

本研究旨在调查脱氢表雄酮(DHEA)对缺血性心力衰竭大鼠心房颤动的保护作用。通过结扎SD大鼠左前降支冠状动脉建立心力衰竭动物模型。手术1周后,通过食道电刺激技术诱发房颤大鼠模型。建模后以15 mg·kg-1·d-1的剂量对大鼠灌胃DHEA,共灌胃4周。分别检测各组大鼠的房颤诱发率、房颤持续时间、左室射血分数(EF)和左室缩短分数(FS)。用天狼星红-快绿染色试剂对大鼠心脏组织进行染色。通过蛋白质印迹分析心脏组织中collagenⅠ、collagenⅢ、α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶9(MMP-9)和金属蛋白酶组织抑制剂1(TIMP-1)的蛋白表达。通过免疫组织化学分析心脏组织中心肌间隙连接蛋白43(Cx43)、Cx40和α-SMA的阳性表达。通过酶联免疫吸附法测定血清中白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平。研究显示,DHEA降低了心力衰竭大鼠的房颤诱发率和房颤持续时间。DHEA升高了EF和FS。DHEA减少了左心房纤维化区域和collagenⅠ和collagenⅢ的表达。DHEA增加了左心房中Cx43和Cx40的表达。DHEA降低了血清IL-6和TNF-α的水平。DHEA抑制了α-SMA的表达。DHEA降低了TGF-β1和MMP-9的表达水平,并增加了TIMP-1的表达水平。本研究表明,DHEA可以通过抑制左心房纤维化、上调心肌间隙连接蛋白表达、减少肌成纤维细胞分化、降低炎症因子水平来降低房颤易感性并提高心功能。

This study aimed to investigate the protective effect of dehydroepiandrosterone(DHEA)on atrial fibrillation in rats with ischemic heart failure.An animal model of heart failure was established by ligating the left anterior descending coronary artery of SD rats.One week after the operation,the rat model of atrial fibrillation was induced by esophageal electrical stimulation technique.After modeling,the rats were given DHEA at a dose of15 mg·kg-1·d-1 for 4 weeks.Then the atrial fibrillation induction rate,atrial fibrillation duration,left ventricular ejection fraction(EF)and left ventricular shortening fraction(FS)of each group were detected,respectively.The rat heart tissue was stained with Sirius red-fast green staining reagent.Western blotting were used to analysis the expression of collagenⅠ,collagenⅢ,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),matrix metalloproteinase 9(MMP-9)and metalloproteinase tissue inhibition agent 1(TIMP-1)protein.The positive expressions of myocardial gap junction protein 43(Cx43),Cx40 andα-SMA in cardiac tissue were analyzed by immunohistochemistry.The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum were determined by enzyme-linked immunosorbent assay.Studies showed that DHEA reduced the induction rate and duration of atrial fibrillation in heart failure rats.DHEA increased EF and FS.DHEA reduced the left atrial fibrosis area and the expression of collagenⅠand collagenⅢ.DHEA increased the expression of Cx43 and Cx40 in the left atrium.DHEA reduced the levels of serum IL-6 and TNF-α.DHEA inhibited the expression ofα-SMA.DHEA decreased the expression levels of TGF-β1 and MMP-9,and increased the expression level of TIMP-1.This study shows that DHEA can reduce susceptibility to atrial fibrillation and improve cardiac function by inhibiting left atrial fibrosis,up-regulating myocardial gap junction protein expression,reducing myofibroblast differentiation,and reducing inflammatory factor levels.