HDAC8在异丙肾上腺素诱导大鼠心肌纤维化中的作用

The role of HDAC 8 in isoprenaline-induced myocardial fibrosis of rat

目的初步探讨组蛋白去乙酰化酶(HDAC8)在盐酸异丙肾上腺素(ISO)诱导的大鼠心肌纤维化中表达的机制。方法将40只雄性SD大鼠随机均等分为正常组和模型组。模型组给予ISO 1次/d(5 mg/kg),正常组予以等剂量生理盐水皮下注射,连续注射7 d后处死大鼠取血液标本,并取心肌组织。测定心脏质量指数;ELISA法检测血清中I型胶原和Ⅲ型胶原的含量;HE和Masson染色法观察心肌纤维化程度;Western blot法测定HDAC8和α-平滑肌肌动蛋白(α-SMA)蛋白表达情况;qRT-PCR法检测HDAC8 mRNA的表达。结果与正常组比较,模型组心脏质量指数明显增加(P<0.05);HE和Masson染色显示模型组心肌组织出现明显的胶原纤维增生;模型组血清标本中Ⅰ型胶原和Ⅲ型胶原的含量较正常组明显增加(P<0.05);Western blot法检测显示模型组HDAC8、α-SMA的蛋白表达明显高于正常组(P<0.05,P<0.01);qRT-PCR检测模型组HDAC8 mRNA表达明显高于正常组(P<0.05)。结论 HDAC8在心肌纤维化中高表达,而在正常心肌组织中低表达,提示其在心肌纤维化的发生发展中可能发挥作用。

Objective To preliminarily study the expression and the role of histone deacetylase 8 （ HDAC8 ） of i-soprenaline induced myocardial fibrosis in rats. Methods The 40 male SD rats were randomly divided into normal group and the experimental model group. The model group was treated subcutaneously with 5 mg/kg isoprenaline daily for 7 d;the normal group was given the same amount of normal saline at the same time. Rats were executed to obtain blood samples and myocardial tissue after 7 d. And HW/BW, LVW/BW were tested. ELISA was used to detected the content of type I collagen and type III collagen in serum. The degree of myocardial fibrosis was ob-served with HE and Masson staining method. The expressions of HDAC8 andα-SMA were tested by Western blot. The mRNA expressions ofα-SMA and HDAC8 were examined by qRT-PCR. Results HW/BW and LVW/BW in-creased significantly in the model group compared with the normal group（P〈0. 05）. The content of type I collagen and type III collagen in serum increased significantly in the model group compared with the normal group （ P 〈0. 05 ） . HE and Masson staining showed myocardial tissue in the model group appeared obviously collagen fiber hy-perplasia. The expressions of HDAC8 and α-SMA in the model group were higher than the normal group （ P 〈0. 05 ） . qRT-PCR detection of mRNA expression of HDAC8 model group was significantly higher than the normal group （ P〈0. 05 ） . Conclusion The HDAC8 is highly expressed in myocardial fibrosis but lowly expressed in nor-mal myocardium suggesting that it may play a role in the development of myocardial fibrosis.