出 处:《华中科技大学学报(医学版)》2018年第2期140-144,177,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基 金:广东省中医药局科研项目(No.20151118)
摘 要:目的观察中药心康方对阿霉素诱导心力衰竭大鼠心肌胶原代谢的影响。方法阿霉素腹腔注射法建立大鼠心力衰竭模型,随机分为假手术组、模型组、心康方组和卡托普利组,观察大鼠心功能和左室重构指标,Masson染色观察心肌胶原变化,Western blot检测心肌Ⅰ型、Ⅲ型胶原、TGF-β1、IκB和p56的表达,Western blot和RT-qPCR分别检测心肌MMP-2、MMP-9、TIMP-1和TIMP-2的蛋白和mRNA表达水平。结果与假手术组比较,模型组大鼠心肌Ⅰ型和Ⅲ型胶原表达明显增加,胶原容积分数明显升高(均P<0.01);TGF-β1和p56表达明显增加,IκB明显降低(均P<0.05);MMP-2、MMP-9和TIMP-1和TIMP-2的蛋白和mRNA表达水平明显升高(P<0.05或P<0.01);心输出量、左室短轴缩短率和射血分数明显降低(均P<0.01),左室舒张末期容积、左室收缩末期容积和左室质量指数明显升高(均P<0.01)。与模型组比较,心康方组和卡托普利组大鼠心肌Ⅰ型和Ⅲ型胶原表达明显减少,胶原容积分数明显降低(均P<0.01);TGF-β1和p56明显降低,IκB明显升高(均P<0.05);MMP-2、MMP-9和TIMP-1和TIMP-2的蛋白和mRNA表达水平明显降低(P<0.05或P<0.01);心输出量、左室短轴缩短率和射血分数明显增加(均P<0.01),左室舒张末期容积、左室收缩末期容积和左室质量指数明显降低(均P<0.01)。结论中药心康方可以减轻阿霉素诱导心力衰竭大鼠的心肌胶原沉积,减轻其左室重构,改善心功能,其机制可能与抑制NF-κB介导的TGF-β1上调有关。Objective To investigate the effects of Xinkang recipe on myocardial collagen metabolism in rats with doxorubicin-induced heart failure.Methods Male SD rats were randomly divided into sham operation group(sham group),model group,Xinkang group and captopril group.The rat model of heart failure was established by intraperitoneal injection of doxorubicin.Distilled water,Xinkang decoction and captopril were respectively administrated to rats by gavage for 35 d.The indexes of ventricular remodeling and cardiac function were measured.Myocardial fibrosis was assessed by Masson’s trichrome staining.The expression levels of collagenⅠ,collagenⅢ,TGF-β1,IκB and p56 were detected in myocardial tissues by Western blotting.Myocardial protein and mRNA levels of matrix metalloproteinase-2(MMP-2),MMP-9,and tissue inhibitor of matrix metalloproteinase-1(TIMP-1)and TIMP-2 were detected by Western blotting and RT-qPCR,respectively.Results The expression levels of collagenⅠand collagenⅢprotein,the collagen volume fraction(CVF),and the expression levels of TGF-β1 and p56 protein were significantly increased(P<0.01),and the expression level of IκB protein was significantly decreased in the model group as compared with the sham group(P<0.05 for all).The myocardial protein and mRNA levels of MMP-2,MMP-9,TIMP-1,and TIMP-2 were significantly higher in the model group than in sham group(P<0.05 or P<0.01).The cardiac output(CO),left ventricular fractional shortening(FS),and left ventricular ejection fraction(LVEF)were significantly lower while the left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),and left ventricular mass index(LVMI)were significantly higher in model group than in sham group(P<0.01).Compared with the model group,the expression levels of collagenⅠand collagenⅢprotein,the CVF and the TGF-β1 and p56 expression levels were significantly decreased and the IκB protein expression was significantly increased in Xinkang and the captopril groups(P<0.05).The myocardial protein a
关 键 词:心康方 心力衰竭 心肌胶原 核因子-ΚB 转化生长因子Β1
分 类 号:R541.6[医药卫生—心血管疾病]
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