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慢性心力衰竭(CHF)是心血管疾病常见的晚期改变,是与衰老有关的慢性疾病之一。近年来虽然CHF在治疗上有一定的进展,但其发病率及死亡率仍处于上升趋势[1]。CHF现治疗上主要从改变神经激素环境抑制交感神经兴奋、肾素-血管紧张素-醛固酮系统活性来降低心肌重构[2],从而延缓心力衰竭进展和降低死亡率。目前许多文章报道心血管疾病中的氧化应激会导致线粒体功能受损,导致心肌细胞能量供应不足,影响心肌细胞正常收缩功能,加快心力衰竭进展[3]。线粒体融合蛋白-2(Mfn2)位于线粒体外膜,能调节线粒体融合和分裂的蛋白质,所以对维持线粒体正常功能起着重要作用[4]。同样乙醛脱氢酶2(ALDH2)是能够抑制机体氧化应激,维持正常线粒体功能的关键酶,能够调节心肌细胞凋亡、纤维化来延缓心力衰竭进展[5]。临床研究中关于Mfn2、ALDH2与CHF病人的相关性研究尚不明确。本文针对Mfn2、ALDH2与CHF病人的相关性研究进行研究,为CHF的诊断及治疗探索提供参考。
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2组研究对象的性别、年龄、天门冬氨酸氨基转移酶、三酰甘油等生化标志比较差异均无统计学意义(P>0.05);CHF组白细胞水平高于对照组, 丙氨酸氨基转移酶和血肌酐低于对照组,差异均有统计学意义(P < 0.05~P < 0.01)(见表 1)。
分组 n 男 女 年龄/岁 白细胞/(×109/L) 丙氨酸氨基转移酶/(U/L) 天门冬氨酸转移酶/(U/L) 三酰甘油/(mmol/L) 血肌酐/(μmol /L) 对照组 40 21 19 69.50±1.59 6.98±0.28 31.13±2.06 32.90±1.42 1.48±0.12 74.28±1.81 CHF组 180 97 83 69.07±0.93 7.47±2.84 29.41±1.37 32.54±1.47 1.51±0.06 73.21±1.37 t — 0.03* 1.65* 2.27* 5.04* 1.41 1.54* 3.52* P — >0.05 >0.05 < 0.05 < 0.01 >0.05 >0.05 < 0.01 *示t′值 表 1 2组病人一般资料比较(x±s)
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与对照组比较,Mfn2、ALDH2、LVEF在CHF组中降低,NT-proBNP、LVEDD在CHF组中增高,差异均有统计学意义(P < 0.01)。CHF心功能Ⅱ级、Ⅲ级、Ⅳ级病人组间比较,Mfn2、ALDH2随着心功能降低而降低,NT-proBNP、LVEDD逐级增高,差异均有统计学意义(P < 0.01)(见表 2)。
分组 n Mfn2/(ng/mL) ALDH2/(U/L) NT-proBNP/(pg/mL) LVEF/% LVEDD/mm 对照组 40 8.11±0.30 112.45±3.77 33.85±2.27 56.73±1.11 48.40±0.34 CHF心功能Ⅱ级组 46 6.47±0.16** 95.26±2.50** 2 724.92±632.58** 48.65±1.62** 52.41±1.50** CHF心功能Ⅲ级组 63 5.91±0.15**△△ 78.58±2.45**△△ 4 803.33±593.0**△△ 42.38±1.71**△△ 56.21±1.26**△△ CHF心功能Ⅳ级组 71 5.46±0.14**△△## 75.52±1.96**△△## 7 111.02±1 027.25**△△## 42.85±1.23**△△ 57.04±1.20*△△## F — 1 860.63 2 089.74 898.43 1 018.59 547.52 P — < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 MS组内 — 0.034 6.836 526 280.11 2.098 1.412 q检验:与对照组比较*P < 0.05, **P < 0.01;与心功能Ⅱ级组比较△△P < 0.01;与心功能Ⅲ级组##P < 0.01 表 2 2组研究对象的血清Mfn2、ALDH2水平及相关指标比较(x±s)
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CHF组中,LVEF≤40%病人为72例,LVEF>40%病人为108例; LVEF≤40%病人组Mfn2、ALDH2低于LVEF>40%病人,NT-proBNP、LVEDD高于LVEF>40%病人,差异均有统计学意义(P < 0.05~P < 0.01)(表 3)。
分组 n Mfn2/(ng/mL) ALDH2/(U/L) NT-proBN/(pg/mL) LVEDD/mm LVEF≤40%组 72 5.450±1.23 76.54±17.70 6 825.42±960.58 63.26±1.11 LVEF>40%组 108 6.16±1.18 85.03±19.85 4 087.11±505.82 50.44±0.67 t — 3.91 2.93 2.52 9.83 P — < 0.01 < 0.01 < 0.05 < 0.01 表 3 LVEF下降和保留的CHF病人的各项检测指标比较(x±s)
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经Pearson相关分析,CHF组中,Mfn2与LVEDD呈负相关(P < 0.01),与LVEF呈正相关(P < 0.01),与NT-proBNP无相关性;ALDH2与LVEF呈正相关(P < 0.01),与NT-proBNP、LVEDD无相关性(见表 4)。
指标 MFN2 ALDH2 r P r P NT-proBNP -0.034 >0.05 -0.141 >0.05 LVEF 0.196 < 0.01 0.282 < 0.01 LVEDD -0.212 < 0.01 -0.124 >0.05 表 4 Mfn2、ALDH2与NT-proBNP、LVEFLVEF和LVEDD的相关性分析
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通过ROC曲线分析,ALDH2诊断CHF的ROC曲线下面积为0.831,95%CI为0.762~0.900(P < 0.05), 当ALDH2取值48.710 U/L时,敏感度为1.00,特异度为1.00。Mfn2诊断CHF的ROC曲线下面积为0.803,95%CI为0.719~0.887(P < 0.05), 当Mfn2取值2.377 ng/mL时,敏感度为1.00,特异度为1.00。将Mfn2、ALDH2两者联合起来诊断得到预测概率,其诊断CHF的ROC曲线下面积为0.891,95%CI为0.823~0.958(P < 0.05)(见图 1)。
血清线粒体融合蛋白-2和乙醛脱氢酶2与慢性心力衰竭的相关性研究
Study on the correlation between serum levels of mitochondrial fusion protein-2, acetaldehyde dehydrogenase 2 and chronic heart failure
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摘要:
目的探讨线粒体融合蛋白-2(Mfn2)、乙醛脱氢酶2(ALDH2)与慢性心力衰竭(CHF)病人的相关性研究。 方法入选CHF病人180例和健康体检人(对照组)40名。其中CHF病人按NYHA心功能分级标准将病人分为Ⅱ级46例、Ⅲ级63例、Ⅳ级71例。入院后完善NT-proBNP、心脏彩超等结果,并留取血清检测Mfn2、ALDH2水平,分析Mfn2、ALDH2与CHF病人相关性。 结果与对照组比较,Mfn2、ALDH2、LVEF在CHF组中降低,NT-proBNP、LVEDD在CHF组中增高,差异均有统计学意义(P 0.01)。CHF心功能Ⅱ级、Ⅲ级、Ⅳ级病人组间比较,Mfn2、ALDH2随着心功能降低而降低,NT-proBNP、LVEDD逐级增高,差异均有统计学意义(P < 0.01)。按照左心室射血分数(LVEF)分级发现,LVEF≤40%病人组Mfn2、ALDH2低于LVEF>40%病人,NT-proBNP、LVEDD高于LVEF>40%病人,差异均有统计学意义(P < 0.05~P < 0.01);经Pearson相关分析,CHF组中,Mfn2与LVEDD呈负相关关系(P < 0.01),与LVEF呈正相关关系(P < 0.01),ALDH2与LVEF呈正相关关系(P < 0.01);与进一步分析Mfn2、ALDH2以及联合诊断CHF的受试者工作特征曲线下面积分别为0.803、0.831、0.891(P < 0.05)。 结论CHF病人随着心功能减退,血清中的Mfn2、ALDH2水平随着减低;Mfn2、ALDH2与CHF相关指标具有相关性,从而对临床评估病情及诊断可能有重要作用。 Abstract:ObjectiveTo investigate the correlation between the levels of mitochondrial fusion protein-2(Mfn2), acetaldehyde dehydrogenase 2(ALDH2) and chronic heart failure(CHF). MethodsOne hundred and eighty CHF patients and 40 healthy people(control group) were investigated.According to the NYHA heart function classification standard, the CHF patients were divided into the class Ⅱ in 46 cases, class Ⅲ in 63 cases and class Ⅳ in 71 cases.After admission, the results of NT-proBNP and cardiac color Doppler ultrasound were improved, the serum levels of Mfn2 and ALDH2 were detected, and the correlation between Mfn2, ALDH2 and CHF was analyzed. ResultsCompared with the control group, the serum levels of Mfn2, ALDH2 and LVEF decreased, the serum levels of NT-proBNP and LVEDD increased in the CHF group, and the differences of which were statistically significant(P < 0.01).Among the class Ⅱ, Ⅲ and Ⅳ heart function groups, the serum levels of Mfn2 and ALDH2 decreased with the decreasing of heart function, the serum levels of NT-proBNP and LVEDD increased with the increasing of heart function, and the differences of which were statistically significant(P < 0.01).According to the LVEF classification, the serum levels of Mfn2 and ALDH2 in patients with LVEF ≤ 40% were lower than those in patents with LVEF>40%, and the levels of NT-proBNP and LVED in patients with LVEF ≤ 40% were higher than those in patents with LVEF>40%(P < 0.05 to P < 0.01).The results of Pearson correlation analysis showed that the level of Mfn2 was negatively correlated with LVEDD(P < 0.01), and positively correlated with LVEF(P < 0.01), while the level of ALDH2 was positively correlated with LVEF(P < 0.01).The area under ROC curve of Mfn2, ALDH2 and both combination in the diagnosis of CHF were 0.803, 0.831 and 0.891(P < 0.05). ConclusionsWith the decreasing of cardiac function in CHF patients, the serum levels of Mfn2 and ALDH2 decrease.The Serum levels of Mfn2, ALDH2 are related to the CHF, which may play an important role in clinical assessment and diagnosis. -
表 1 2组病人一般资料比较(x±s)
分组 n 男 女 年龄/岁 白细胞/(×109/L) 丙氨酸氨基转移酶/(U/L) 天门冬氨酸转移酶/(U/L) 三酰甘油/(mmol/L) 血肌酐/(μmol /L) 对照组 40 21 19 69.50±1.59 6.98±0.28 31.13±2.06 32.90±1.42 1.48±0.12 74.28±1.81 CHF组 180 97 83 69.07±0.93 7.47±2.84 29.41±1.37 32.54±1.47 1.51±0.06 73.21±1.37 t — 0.03* 1.65* 2.27* 5.04* 1.41 1.54* 3.52* P — >0.05 >0.05 < 0.05 < 0.01 >0.05 >0.05 < 0.01 *示t′值 表 2 2组研究对象的血清Mfn2、ALDH2水平及相关指标比较(x±s)
分组 n Mfn2/(ng/mL) ALDH2/(U/L) NT-proBNP/(pg/mL) LVEF/% LVEDD/mm 对照组 40 8.11±0.30 112.45±3.77 33.85±2.27 56.73±1.11 48.40±0.34 CHF心功能Ⅱ级组 46 6.47±0.16** 95.26±2.50** 2 724.92±632.58** 48.65±1.62** 52.41±1.50** CHF心功能Ⅲ级组 63 5.91±0.15**△△ 78.58±2.45**△△ 4 803.33±593.0**△△ 42.38±1.71**△△ 56.21±1.26**△△ CHF心功能Ⅳ级组 71 5.46±0.14**△△## 75.52±1.96**△△## 7 111.02±1 027.25**△△## 42.85±1.23**△△ 57.04±1.20*△△## F — 1 860.63 2 089.74 898.43 1 018.59 547.52 P — < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 MS组内 — 0.034 6.836 526 280.11 2.098 1.412 q检验:与对照组比较*P < 0.05, **P < 0.01;与心功能Ⅱ级组比较△△P < 0.01;与心功能Ⅲ级组##P < 0.01 表 3 LVEF下降和保留的CHF病人的各项检测指标比较(x±s)
分组 n Mfn2/(ng/mL) ALDH2/(U/L) NT-proBN/(pg/mL) LVEDD/mm LVEF≤40%组 72 5.450±1.23 76.54±17.70 6 825.42±960.58 63.26±1.11 LVEF>40%组 108 6.16±1.18 85.03±19.85 4 087.11±505.82 50.44±0.67 t — 3.91 2.93 2.52 9.83 P — < 0.01 < 0.01 < 0.05 < 0.01 表 4 Mfn2、ALDH2与NT-proBNP、LVEFLVEF和LVEDD的相关性分析
指标 MFN2 ALDH2 r P r P NT-proBNP -0.034 >0.05 -0.141 >0.05 LVEF 0.196 < 0.01 0.282 < 0.01 LVEDD -0.212 < 0.01 -0.124 >0.05 -
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