核酸氧化与高龄老年射血分数保留心力衰竭的相关性研究

Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years

目的探讨高龄老年射血分数保留心力衰竭(HFpEF)患者心肌组织核酸氧化程度及其与淀粉样物质沉积的相关性。方法本研究为回顾性病例对照研究, 病例资料来源于2003—2017年北京医院病理科资料库中的系统病理解剖资料和临床资料。纳入26例≥85岁HFpEF患者为HFpEF组, 并将年龄和性别匹配、生前未诊断心力衰竭且死于非心血管疾病的患者13例作为对照组。取两组的左心室心肌切片进行8-氧化鸟嘌呤核苷(8-oxo-G)和8-氧化鸟嘌呤脱氧核苷(8-oxo-dG)免疫组织化学染色并进行半定量分析, 评估心肌细胞RNA和DNA氧化情况。以8-oxo-G免疫组织化学染色平均吸光度的中位数为界值, 将所有患者分为高值组和低值组, 采用刚果红染色法比较两组心肌淀粉样物质沉积情况。结果 HFpEF组患者年龄(91.8±3.7)岁, 男性24例(92.3%);对照组年龄(91.7±3.7)岁, 男性11例(84.6%)。HFpEF组心肌组织8-oxo-G免疫组织化学染色平均吸光度为0.313 8(0.302 2, 0.340 6), 高于对照组的0.289 2(0.276 7, 0.299 4), 差异有统计学意义(Z=-3.245, P=0.001);HFpEF组心肌组织8-oxo-dG免疫组织化学染色的平均吸光度为0.300 0(0.290 0, 0.322 5), 对照组为0.300 0(0.290 0, 0.320 0), 差异无统计学意义(Z=-0.454, P=0.661)。8-oxo-G免疫组织化学染色平均吸光度高值组患者心肌刚果红染色中重度阳性的比例(85.0%, 17/20)高于低值组(31.6%, 6/19)(P=0.001)。结论≥85岁老年HFpEF患者心肌组织RNA氧化程度高于同龄非心力衰竭老年人, RNA氧化程度高的患者心脏淀粉样物质沉积更多。

Objective To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction(HFpEF)and the correlation with myocardial amyloid deposition.Methods This was a retrospective case-control study.Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected.Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group.The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside(8-oxo-G)and 8-oxidized guanine deoxyriboside(8-oxo-dG)to evaluate the oxidation of RNA and DNA in cardiomyocytes.Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value,patients were divided into high-absorbance group and low-absorbance group.Congo red staining was used to compare myocardial amyloid deposition between the two groups.Results The mean age of patients in HFpEF group was(91.8±3.7)years,24(92.3%)were males.The mean age of patients in control group was(91.7±3.7)years old,11(84.6%)were males.The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group(0.3138(0.3022,0.3406)vs.0.2892(0.2767,0.2994),Z=-3.245,P=0.001).The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups(0.3000(0.2900,0.3225)vs.0.3000(0.2900,0.3200),Z=-0.454,P=0.661).Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group((85.0%,17/20)vs.(31.6%,6/19),P=0.001).Conclusion The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure.Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.