二十二碳六烯酸对房颤大鼠心房纤维化的影响
Effect of docosahexaenoic acid on atrial fibrosis in atrial fibrillation rats
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摘要: 目的：探讨二十二碳六烯酸（docosahexaenoic acid，DHA）对大鼠心房颤动模型心房纤维化的影响，及其对细胞外信号调节激酶1/2（extracellular signal-regulated kinase 1/2，ERK1/2）蛋白、磷酸化细胞外信号调节激酶1/2（phosphorylated extracellular signal-regulated kinase 1/2，p-ERK1/2）蛋白、Ⅰ型胶原mRNA和蛋白表达的影响。方法：将80只乙酰胆碱-氯化钙混合液敏感大鼠随机分为对照组（CTL组）、对照DHA处理组（DHA组）、房颤组（AF组）和房颤DHA处理组（DHA+AF组），各20只。观察各组大鼠房颤持续时间，采用Masson染色法观察大鼠心房组织胶原纤维增生情况，应用Real-time PCR法测定大鼠心房组织中Ⅰ型胶原mRNA表达，Western blot法测定大鼠心房组织中Ⅰ型胶原、ERK1/2和p-ERK1/2蛋白表达。结果：实验第10、17天，DHA+AF组大鼠房颤持续时间均明显短于AF组（P<0.01）。与CTL组比较，AF组大鼠心房肌间质可见大量胶原纤维增生，心房纤维化程度高；DHA+AF组大鼠心房肌间质可见少量胶原纤维增生，心房纤维化程度较AF组降低。与CTL组比较，AF组大鼠P-ERK1/2与ERK1/2比值升高（P<0.05），DHA组比值降低（P<0.05），而CTL组与DHA+AF组差异无统计学意义（P>0.05）；与AF组比较，DHA组和DHA+AF组与P-ERK1/2与ERK1/2比值均降低（P<0.05）。与CTL组比较，AF组和DHA+AF组大鼠心房组织Ⅰ型胶原mRNA和蛋白表达水平均升高（P<0.05~P<0.01）；与AF组比较，DHA+AF组大鼠心房组织Ⅰ型胶原mRNA和蛋白表达水平均降低（P<0.05）。结论：DHA具有改善SD大鼠房颤模型心房纤维化的作用，此作用与其抑制心房组织ERK1/2通路的活性进而下调心房组织Ⅰ型胶原mRNA和蛋白的表达有关。
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关键词:
- 心房颤动 /
- 二十二碳六烯酸 /
- 心房纤维化 /
- 细胞外信号调节激酶1/2 /
- Ⅰ型胶原
Abstract: Objective:To investigate the effects of docosahexaenoic acid(DHA) on the atrial fibrosis in atrial fibrillation rats,and mRNA and protein levels of extracellular signal-regulated kinase 1/2(ERK1/2),phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2) and type Ⅰ collagen.Methods:Eighty Sprague-Dawley (SD) rats sensitive to acetylcholine-calcium chloride mixture were randomly divided into the control group(CTL group),control treated with DHA group(DHA group),atrial fibrillation group(AF group) and atrial fibrillation treated with DHA group(DHA+AF group) (20 rats each group).The duration of atrial fibrillation in each group was measured.The atrial collagen fiber hyperplasia in rats were detected using Masson staining.The mRNA expression of type Ⅰ collagen in atrial tissue was detected using the quantitative real-time PCR,and the protein levels of ERK1/2,p-ERK1/2 and type Ⅰcollagen in atrial tissue were detected by Western blot.Results:At 10 and 17 days of experiment,the duration of atrial fibrillation in (DHA+AF) group was significantly shorter than that in AF group(P<0.01).Compared with the CTL group,a lot of collagen fibers proliferation in atrial interstitium were found,and the interstitial fibrosis in atrial was higher in AF group.Compared with the AF group, a little collagen fibers proliferation in atrial interstitium was found,and the interstitial fibrosis in atrial was lower in (DHA+AF) group.Compared with the CTL group,the ratio of p-ERK1/2 to ERK1/2 increased in AF group(P<0.05),which in DHA group decreased(P<0.05),and the difference of which between CTL group and(DHA+AF) group was not statistically significant(P>0.05).Compared with the AF group,the ratio of p-ERK1/2 to ERK1/2 decreased in (DHA+AF) group(P<0.05).Compared with the CTL group,the mRNA and protein levels of type Ⅰ collagen in atrial tissue increased in AF group and (DHA+AF) group(P<0.05 to P<0.01).Compared with the AF group,the mRNA and protein levels of type Ⅰ collagen in atrial tissue decreased in(DHA+AF) group(P<0.05).Conclusions:DHA can improve the atrial fibrosis in atrial fibrillation rats,the mechanism of which may be related to the mRNA and protein expressions of type Ⅰcollagen down-regulating by inhibiting the ERK1/2 activation in atrial tissue. -
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