骨保护蛋白/核因子-κβ受体活化因子/核因子-κβ受体活化因子配体轴与心脏瓣膜病合并持续性心房颤动患者改良迷宫术后心房颤动复发的关系及其作用机制研究

Relationship and Mechanism of Action of OPG/RANK/RANKL Axis with Recurrence of Atrial Fibrillation after Modified Maze Procedure in Patients with Valvular Heart Disease with Persistent Atrial Fibrillation

背景目前研究表明,心脏瓣膜病合并心房颤动(简称房颤)患者改良迷宫术后短期复发可能与心房结构重构有关,探讨该类患者术后房颤复发的可能机制具有一定的临床意义。目的探讨骨保护蛋白(OPG)/核因子-κβ受体活化因子(RANK)/核因子-κβ受体活化因子配体(RANKL)轴与心脏瓣膜病合并持续性房颤患者改良迷宫术后房颤复发的关系及其作用机制。方法选取2016年7月—2019年6月因心脏瓣膜病合并持续性房颤于宜兴市人民医院和南京鼓楼医院行改良迷宫术后转复为窦性心律(简称窦律)患者64例,根据术后3个月时房颤复发情况分为房颤复发组(AF组)27例和窦律维持组(SR组)37例。比较两组患者术前血清OPG、可溶性RANKL(sRANKL)水平、sRANKL/OPG及左心耳组织中基质金属蛋白酶9(MMP-9)、基质金属蛋白水解酶组织抑制因子1(TIMP-1)水平、MMP-9/TIMP-1,并采用Pearson相关分析探讨患者血清sRANKL/OPG与左心耳组织中MMP-9、TIMP-1水平及MMP-9/TIMP-1的关系。结果AF组患者术前血清sRANKL、OPG水平及左心耳组织中MMP-9水平高于SR组,血清sRANKL/OPG、左心耳组织中MMP-9/TIMP-1大于SR组(P<0.05)。Pearson相关分析结果显示,AF组患者血清sRANKL/OPG与左心耳组织中MMP-9/TIMP-1呈正相关(r=0.757,P<0.001),与左心耳组织中MMP-9(r=0.341)、TIMP-1(r=0.190)水平无相关性(P>0.05);SR组患者血清sRANKL/OPG与左心耳组织中MMP-9(r=0.193)、TIMP-1(r=0.107)水平和MMP-9/TIMP-1(r=0.180)无相关性(P>0.05)。结论OPG/RANK/RANKL轴活性增加可能通过调控MMP/TIMP系统影响心房间质纤维化,促进心房结构重构,从而增加心脏瓣膜病合并持续性房颤患者改良迷宫术后房颤复发风险,不利于窦律维持。

Background Current research shows that,recurrence of atrial fibrillation(AF)after modified maze procedure may be related to atrial structural remodeling in patients with valvular heart disease complicated with persistent AF.It is of clinical significance to explore the possible mechanism of recurrence of AF after operation.Objective To investigate the relationship of OPG/RANK/RANKL axis with recurrence of AF after modified maze procedure in patients with valvular heart disease complicated with persistent AF and the mechanism of action.Methods A total of 64 patients who recovered sinus rhythm after modified maze procedure for valvular heart disease with persistent AF were recruited from Yixing People's Hospital and Nanjing Drum Tower Hospital from July 2016 to June 2019,including 27 cases with AF recurrence(AF group)and 37 cases with maintained sinus rhythm(SR group)within 3 months postoperatively.Serum levels of OPG and sRANKL,and sRANKL/OPG ratio,and MMP-9,TIMP levels,and MMP-9/TIMP-1 ratio in the left atrial appendage were compared between the two groups.The relationships of serum sRANKL/OPG with MMP-9,TIMP-1,and MMP-9/TIMP-1 ratio in the left atrial appendage were analysed by Pearson correlation analysis.Results AF group had significantly higher serum levels of preoperative sRANKL and OPG and MMP-9 in the left atrial appendage,and much greater serum sRANKL/OPG ratio and MMP-9/TIMP-1 ratio in the left atrial appendage than SR group(P<0.05).Pearson correlation analysis results showed that,serum sRANKL/OPG ratio was positively correlated with MMP-9/TIMP-1 ratio in the left atrial appendage(r=0.757,P<0.001),but had no correlation with MMP-9(r=0.341)or TIMP-1(r=0.190)in the left atrial appendage in AF group(P>0.05).Moreover,there was no correlation between serum sRANKL/OPG ratio and MMP-9(r=0.193),TIMP-1(r=0.107)or MMP-9/TIMP-1 ratio in the left atrial appendage(r=0.180)in the left atrial appendage in SR group(P>0.05).Conclusion Increased activity of OPG/RANK/RANKL axis may affect the atrial interstitial fibrosis and aggravate the atrial structural remodeling by regulating MMP/TIMP system,leading to increased risk of recurrence of AF after modified maze procedure in patients with valvular heart disease with persistent AF,which is unfavorable for the maintenance of sinus rhythm.