川芎嗪对血管紧张素Ⅱ诱导大鼠心脏成纤维细胞纤维化的影响  

The Influence of Ligustrazine on Cardiac Fibroblasts Fibrosis Induced by Angiotensin Ⅱ in Rats

作　　者：常煜胤 路明[1] 卢太苓 丁洁[1] 

机构地区：[1]徐州医学院,江苏徐州221000

出　　处：《中西医结合心脑血管病杂志》2016年第23期2758-2761,共4页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的探讨川芎嗪(ligustrazine)对血管紧张素Ⅱ(AngⅡ)诱导心脏成纤维细胞纤维化的机制及影响。方法体外培养SD大鼠乳鼠CFs,实验分为5组,A组(对照组):培养时不加干预药物;B组(AngⅡ组):加AngⅡ10-6mol/L;C组(川芎嗪低剂量组):AngⅡ10-6mol/L+川芎嗪5 mg/L;D组(川芎嗪中剂量组)AngⅡ10-6mol/L+川芎嗪10 mg/L;E组(川芎嗪高剂量组)AngⅡ10-6mol/L+川芎嗪20 mg/L,干预48 h后,采用RT-PCR法测定α-平滑肌肌动蛋白(α-SMA)及钙调神经磷酸酶催化亚基Aβ亚型(Cn Aβ)mRNA的表达情况;Western Blot法检测α-SMA及活化T细胞核因子3(NFAT3)的蛋白表达情况。结果与A组比较,B组α-SMAmRNA、Cn AβmRNA表达均显著增高,差异有统计学意义(P<0.05),α-SMA、NFAT3蛋白的表达也显著增加,差异有统计学意义(P<0.05);与B组比较,C组α-SMAmRNA、Cn AβmRNA表达差异无统计学意义(P>0.05),α-SMA、NFAT3蛋白表达无统计学意义(P>0.05),D组和E组α-SMA、Cn Aβ的mRNA表达均显著降低,差异有统计学意义(P<0.05),α-SMA、NFAT3蛋白表达显著减少,差异有统计学意义(P<0.05)。结论在一定浓度范围,川芎嗪以剂量依赖方式抑制AngⅡ诱导的SD大鼠CFs心肌纤维化过程,其机制可能与心脏成纤组细胞纤组化川芎嗪抑制CFs的钙调神经磷酸酶(Ca N)信号通路有关。Objective To observe the effect of ligustrazine on angiotensinⅡ（ AngⅡ）-induced cardiac fibroblasts（ CFs） fibrosis and its mechanisms. Methods The CFs of neonatal Sprague-Dawley（ SD） rats were isolated with the method of trypsin digestion and differential anchoring velocity,then cultured in vitro. The generation 2-4 of CFs were used for the experiment and randomly divided into 5 groups which were control group cultured without AngⅡ or ligustrazine（ group A）,AngⅡ group cultured with AngⅡ 10^- 6mol / L（ group B）,and ligustrazine groups（ group C,group D,group E） cultured with AngⅡ 10^- 6mol / L and ligustrazine 5,10,20 mg / L,respectively. CFs were cultured for 48 h and the smooth muscle alpha-actin（ α-SMA）,beta isoform of calcineurin（ Cn Aβ） mRNA expression were examined by reverse transcription polymerase chain reaction（ RT-PCR）,the α-SMA,nuclear factor of activated T-lymphocyte-3（ NFAT3） protein expression by western blot analyses. Results Compared with group A,the expressions of α-SMA,Cn Aβ mRNA and α-SMA,NFAT3 protein were upregulated in group B（ all P〈0.05）. Compared with group B,the expressions of α-SMA,Cn Aβ mRNA and α-SMA,NFAT3 protein in group D and group E were obviously decreased（ all P〈0.05）. Conclusion Within a given concentration range,ligustrazine can inhibit the expression of α-SMA in a dosedependent manner to delay the differentiation of CFs induced by AngⅡ. Ligustrazine can inhibit the expression of Ca N and downstream signaling molecules NFAT3,which indicates that the inhibition of CFs fibrosis process may be related to the Ca N signaling pathway.

关 键 词：心脏成纤维细胞纤维化 川芎嗪 血管紧张素Ⅱ α-平滑肌肌动蛋白 钙调神经磷酸酶催化亚基Aβ亚型 钙调神经磷酸酶信号通路 活化T细胞核因子3 SD大鼠 

分 类 号：R542.2[医药卫生—心血管疾病]