XIRP2和HCN4在心肌脂肪浸润致猝死者心脏传导系统表达研究

Expression of XIRP2 and HCN4 in cardiac conduction system in sudden death caused by myocardial adipose infiltration

目的:研究心肌脂肪浸润致猝死的法医病理学特征及传导组织中含心肌动蛋白重复序列蛋白2(XIRP2)和超极化激活环核苷酸门控阳离子通道4(HCN4)蛋白含量表达变化情况,探讨XIRP2和HCN4蛋白作为心肌脂肪浸润致猝死的潜在分子标记物的可能性。方法:收集某司法鉴定中心2015~2022年死因为心肌脂肪浸润致猝死者8例为猝死组,选取死因为外伤致死者10例为对照组进行统计、归纳和分析。通过大体检查、HE染色和Masson三色染色观察组织病理学改变,免疫组织化学染色(IHC)观察XIRP2和HCN4蛋白表达情况。结果:组织病理学检查示心肌脂肪浸润主要侵犯右心室、窦房结、房室结;IHC结果示猝死组较对照组的XIRP2和HCN4蛋白在窦房结、房室结表达升高,在左右束支表达降低(P<0.05)。心肌脂肪浸润猝死者窦房结和房室结XIRP2和HCN4蛋白表达水平高于左右束支(P<0.05),表达趋势与对照组相反。心肌脂肪浸润猝死者HCN4、XIRP2蛋白表达在窦房结与房室结之间差异有统计学意义。传导系统XIRP2与HCN4蛋白表达相关(P<0.05)。结论:心肌脂肪浸润主要表现为右心室合并窦房结、房室结内大量脂肪浸润,可能通过影响传导系统离子通道蛋白表达致心律失常引起猝死,XIRP2和HCN4蛋白在传导系统的表达差异可为该类案件的法医学鉴定提供参考。

Objective:To study the forensic pathologic characteristics of sudden death caused by myocardial adipose infiltration and the expression of Xin-actin-binding-repeat-containing protein 2(XIRP2)and hyperpolarization activated cyclic nucleotide-gated cation channel 4(HCN4)in order to investigate the possibility of XIRP2 and HCN4 as potential molecular markers of sudden death from myocardial adipose infiltration in forensic identification of similar sudden death cases.Methods:Eight cases of sudden death caused by myocardial adipose infiltration,collected from XXX Center of Forensic Science from 2015 to 2022,were included in the experimental group,and another 10 death cases caused by trauma were included in control group.The related information was summarized and statistically analyzed in all cases in both groups.The pathological changes were observed by gross examination through HE staining and Masson trichromatic staining.The expressions and localization of HCN4 and XIRP2 were observed by immunohistochemical technology(IHC).Results:Histopathological examination revealed that in the cases of sudden death from adipose infiltration of myocardium,the adipose infiltration was mainly observed in right ventricle,sinoatrial node and atrioventricular node.IHC indicated that the expression of HCN4 and XIRP2 in the sudden death group was higher than that of the control group in sinoatrial node and atrioventricular node,yet was exactly opposite in left and right bundle branches(P<0.05).The expression of HCN4 and XIRP2 in the sinoatrial node and atrioventricular node of the sudden death group were higher than that in the left and right bundle branches,which was contrary to the control group(P<0.05).The expression of HCN4 and XIRP2 protein in the sinus node and atrioventricular node of the dead with sudden myocardial adipose infiltration was statistically different.XIRP2 and HCN4 was correlated in the cardiac conduction system(P<0.05).Conclusion:Myocardial adipose infiltration mainly occurs in the right ventricle,sinoatrial node and atrioventricular node,with a mass of myocardial tissue replaced by adipose tissue.Myocardial adipose infiltration may lead to arrhythmia and sudden death by affecting the expression of ion channel proteins in cardiac conduction system.The difference in the expression of XIRP2 and HCN4 in the conduction system may provide potential molecular markers for forensic identification of such cases.