二十二碳六烯酸对房颤大鼠心房纤维化的影响

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。

Effect of docosahexaenoic acid on atrial fibrosis in atrial fibrillation rats

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 typeⅠcollagen 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.