环孢素A对心房颤动大鼠心房有效不应期及血清中MMP-2、TIMP-2水平的影响

目的：探讨环孢素A（cyclosporineA，CsA）对心房颤动（AF）大鼠心房有效不应期（ERP）、血清中基质金属蛋白酶-2（MMP-2）及金属蛋白酶组织抑制剂-2（TIMP-2）水平的影响。方法：将SD大鼠随机分为对照组、AF组、AFCsA处理组。除对照组外，采用乙酰胆碱-氯化钙药物经尾静脉注射法构建AF大鼠模型；对照组静脉注射等体积的0．9％氯化钠注射液。AFCsA处理组饮食加5mg·kg^-1·d^-1CsA；对照组和AF组每天胃内注入等体积的0．9％氯化钠注射液。心电图检测AF持续时间；测定心房ERP；采用ELISA法检测大鼠血清中MMP-2及TIMP-2水平。结果：与对照组比较，AF组心房ERP明显缩短（P〈0．01），血清中MMP-2水平明显增高，TIMP-2水平明显下降（P〈0．01）；与AF组比较，AFCsA处理组AF持续时间明显缩短，心房ERP明显延长（P〈0．01），血清中MMP-2水平明显降低，TIMP-2水平明显升高（P〈0．01）。结论：CsA具有抗AF作用，其可能的机制是延长心房ERP从而改善大鼠心房电重构。以及调控MMP-2及TIMP-2表达而改善大鼠心房结构重构。

Effects of cyclosporine A on atrial effective refractory period,serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 levels in rat atrial fibrillation model

Objective： To study the effects of cyclosporine A （CsA） on atrial effective refractory period （ERP）, serum matrix metalloproteinase-2（ MMP-2 ） and tissue inhibitor of metalloproteinase-2 （TIMP-2） levels in rat atrial fibrillation （AF） model. Methods ：The SD rats were randomized into 3 groups：control group, AF group and CsA treatment group. The rat model with atrial fibrillation was made via tail vein injected with acetycholine and calcium chloride （Ach-CaCl2 ） ;the rats in control groups were injected with an equal amount of normal saline（NS） solution. The rats in CsA treatment group were given with CsA at 5 mg · kg^-1 · d^-1 orally; the rats in AF and control groups were given with an equal amount of NS orally. AF duration time was measured by ECG. All rats were anesthetized and the atriums were immediately excised for measuring ERP;the levels of serum MMP-2 and TIMP-2 were examined by ELISA. Results： The atrial ERP duration time in AF group was shorter than that in control group （ P 〈 0.01 ） ; compared with control group, serum M MP-2 level was increased significantly（ P 〈 0.01 ）, but TIMP-2 level was decreased in AF group（ P 〈 0.01 ）. However, compared with AF group, the duration time of atrial fibrillation in CsA treatment group was shorter significantly （P 〈 0.01 ）, atrial ERP duration time was longer（ P 〈 0.01 ） ; serum MMP-2 level was significantly decreased （ P 〈 0.01 ）, but TIMP-2 level was increased （ P 〈 0.01 ）. Conclusions： CsA may play the anti-atrial fibrillation role in atrial fibrillation rat model, which might be associated with prolonging atrial ERP and regulation of serum MMP-2 and TIMP-2 expressions.