基质金属蛋白酶2、基质金属蛋白酶抑制剂2和可溶性CD44在高度近视眼合并原发性开角型青光眼患者房水中的定量研究

doi:10.3877/cma.j.issn.2095-2007.2019.06.003

目的

研究房水中可溶性白细胞分化抗原44(sCD44)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶抑制剂2(TIMP-2)的水平及MMP-2与TIMP-2比值的变化与高度近视眼(HM)合并原发性开角型青光眼(POAG)发病的相关性。

方法

收集2015年7月至2016年12月期间就诊于解放军总医院第三医学中心的HM、POAG和年龄相关性白内障(CAT)患者47例，根据诊断分为4组，HM合并POAG患者12例(12只眼)作为HMG组；POAG组患者15例(15只眼)作为POAG组；HM患者12例(12只眼)作为HM组；CAT患者8例(8只眼)作为CAT组。以A型超声检查测定眼轴长度。采用双抗体夹心法酶联免疫吸附实验方法测定各组房水中MMP-2、TIMP-2及sCD44的水平。采用单因素方差分析比较各组房水样本之间sCD44、MMP-2、TIMP-2的水平及MMP-2与TIMP-2比值的差异，组间两两比较采用方差分析。采用Pearson相关性检验分析sCD44、MMP-2和TIMP-2之间的相关性及sCD44、MMP-2、TIMP-2与眼轴长度的相关性。

结果

HMG组、HM组、POAG组及CAT组房水中sCD44水平分别为(229.86±14.23) ng/l、(227.96±17.91) ng/l、(187.80±14.14) ng/l及(149.74±19.18) ng/l，MMP-2水平分别为(7.83±1.28) ng/ml、(7.78±0.91) ng/ml、(6.10±0.85) ng/ml及(5.42±0.72) ng/ml，TIMP-2水平分别为(128.08±11.41) ng/ml、(115.20±7.44) ng/ml、(91.89±8.26) ng/ml及(63.22±8.69) ng/ml，TIMP-2/MMP-2比值分别为(16.65±2.44)、(14.95±1.55)、(15.32±2.30)及(11.67±0.49)，比较差异均有统计学意义(F＝53.88，16.05，95.41，9.98；P<0.05)。其中，HMG组、HM组及POAG组房水中sCD44水平较CAT组升高，差异有统计学意义(t＝10.75，9.31，5.12；P<0.05)；HMG组及HM组房水样本中MMP-2的水平较CAT组升高，差异有统计学意义(t＝4.81，6.15；P<0.05)；POAG组房水中MMP-2的水平与CAT组比较，差异无统计学意义(t＝1.86，P>0.05)；HMG组、HM组及POAG组房水中TIMP-2的水平较CAT组升高，差异有统计学意义(t＝13.62，14.33，7.45；P<0.05)；HMG组、HM组及POAG组中TIMP-2/MMP-2的比值均高于CAT组，差异有统计学意义(t＝5.65，5.75，4.39；P<0.05)。相关性分析显示，房水中MMP-2的水平与TIMP-2的水平呈较高度正相关(r＝0.75，P<0.05)。房水中MMP-2的水平与sCD44的水平呈较高度正相关(r＝0.67，P<0.05)。房水中TIMP-2的水平与sCD44的水平呈高度正相关(r＝0.83，P<0.05)；房水中sCD44、MMP-2及TIMP-2的水平与眼轴长度呈正相关(r＝0.90，0.70，0.81；P<0.05)。

结论

HM合并POAG患者、HM患者和POAG患者房水中的sCD44、MMP-2及TIMP-2的水平显著升高，TIMPs/MMPs比例失衡。房水中sCD44、MMP-2及TIMP-2可作为HM合并POAG的早期预警指标。

关键词: 基质金属蛋白酶2, 基质金属蛋白酶抑制剂2, 可溶性白细胞分化抗原44, 高度近视合并原发性开角型青光眼, 房水

Objective

The aim of this study was to explore the correlation among the expression of matrix metalloproteinases-2(MMP-2), tissue inhibitor of metalloproteinases-2(TIMP-2), soluble cluster of differentiation antigen 44(sCD44) and TIMP-2/MMP-2 and the morbidity with HM&POAG.

Methods

Selected 47 objects of high myopia(HM), primary open angle glaucoma(POAG) and age-related cataract(CAT) from July 2015 to December 2016 in the Third Medical Center of Chinese PLA General Hospital. 47 objects were divided into 4 groups according to the diagnosis.12 patients (12 eyes) who were diagnosed as HM and POAG were taken as group HMG; 15 patients (15 eyes) who were diagnosed as POAG were taken as group POAG; 12 patients(12 eyes) who were diagnosed as HM were taken as group HM; 8 patients (8 eyes) who were diagnosed as CAT were taken as group CAT. A-scan ultrasonography was used to measure the length of optic axis. Double antibody sandwich enzyme linked immunosorbent assay was used to determine the concentration of MMP-2, TIMP-2 and sCD44 in aqueous humor. Differences among the level of MMP-2, TIMP-2, sCD44 and TIMP-2/MMP-2 of the four groups were verified by one-way ANOVA analysis; the correlation was verified by Pearson correlation test.

Results

In group HMG, HM, POAG and CAT, the level of sCD44 were (229.86±14.23) ng/l, (227.96±17.91) ng/l, (187.80±14.14) ng/l, (149.74±19.18) ng/l, the level of MMP-2 were (7.83±1.28) ng/ml, (7.78±0.91) ng/ml, (6.10±0.85) ng/ml and (5.42±0.72) ng/ml, the level of TIMP-2 were (128.08±11.41) ng/ml, (115.20±7.44) ng/ml, (91.89±8.26) ng/ml and(63.22±8.69) ng/ml, the ratio of TIMP-2/MMP-2 were (16.65±2.44), (14.95±1.55), (15.32±2.30) and (11.67±0.49), the differences were statistically significant(F=53.878, 16.051, 95.405, 9.984; P<0.05). The difference of the level of sCD44 between each two group of group HMG, HM, POAG and CAT was statistically significant(t=10.75, 9.31, 5.12; P<0.05). The difference of the level of MMP-2 of each two group of group HMG, HM and CAT was statistically significant(t=4.81, 6.15; P<0.05), but was no significantly difference between group POAG and CAT(t=1.86, P>0.05). The difference of the level of TIMP-2 of each two group of group HMG, HM, POAG and CAT was statistically significant(t=13.62, 4.33, 7.45; P<0.05). The difference of the level of TIMP-2 and MMP-2 of each two group of group HMG, HM, POAG and CAT was statistically significant(t=5.65, 5.75, 4.39; P<0.05). The level of TIMP-2 and MMP-2, sCD44 and MMP-2, sCD44 and TIMP-2 were positive correlated (r=0.754, 0.672, 0.829; P<0.05). The concentration of sCD44, MMP-2 and TIMP-2 in aqueous humor was positive correlated with axial length(r=0.896, 0.703, 0.813; P<0.05).

Conclusions

The expressions of sCD44, MMP-2 and TIMP-2 in aqueous humor of patients with POAG&HM or HM or POAG were significantly increased, and the balance of TIMP-2/MMP-2 was broken. The concentration of sCD44, MMP-2 and TIMP-2 in aqueous humor could be used as early warning indicators of high myopia with primary open angle glaucoma.

Key words: Matrix metalloproteinases-2, Tissue inhibitor of metalloproteinases-2, Soluble cluster of differentiation antigen 44, High myopia & primary open angle glaucoma, Aqueous humor

表1 四组患者房水中sCD44、MMP-2及TIMP-2水平的比较(±s)

组别	例数	sCD44(ng/l)	MMP-2(ng/ml)	TIMP-2(ng/ml)	TIMP-2 /MMP-2
HMG组	12	229.86±14.23^*	7.83±1.28^*	128.08±11.41^*	16.65±2.44^*
HM组	12	227.96±17.91^*	7.78±0.91^*	115.20± 7.44^*	14.95±1.55^*
POAG组	15	187.80±14.14^*	6.10±0.85	91.89± 8.26^*	15.32±2.30^*
CAT组	8	149.74±19.18	5.42±0.72	63.22± 8.69	11.67±0.49
F值		53.88	16.05	95.41	9.98
P值		<0.05	<0.05	<0.05	<0.05

表1 四组患者房水中sCD44、MMP-2及TIMP-2水平的比较(±s)

组别	例数	sCD44(ng/l)	MMP-2(ng/ml)	TIMP-2(ng/ml)	TIMP-2 /MMP-2
HMG组	12	229.86±14.23^*	7.83±1.28^*	128.08±11.41^*	16.65±2.44^*
HM组	12	227.96±17.91^*	7.78±0.91^*	115.20± 7.44^*	14.95±1.55^*
POAG组	15	187.80±14.14^*	6.10±0.85	91.89± 8.26^*	15.32±2.30^*
CAT组	8	149.74±19.18	5.42±0.72	63.22± 8.69	11.67±0.49
F值		53.88	16.05	95.41	9.98
P值		<0.05	<0.05	<0.05	<0.05

图1 房水中可溶性白细胞分化抗原44、基质金属蛋白酶2及基质金属蛋白酶2抑制剂的水平与眼轴长度关系的散点图　A图示房水样本中基质金属蛋白酶2水平及基质金属蛋白酶2抑制剂水平散点图；B图示房水样本中可溶性白细胞分化抗原44水平及基质金属蛋白酶2水平散点图；C图示房水样本中可溶性白细胞分化抗原44水平及基质金属蛋白酶2抑制剂水平散点图；D图示房水样本中可溶性白细胞分化抗原44水平及眼轴长度的散点图；E图示房水样本中基质金属蛋白酶2水平及眼轴长度的散点图；F图示房水样本中基质金属蛋白酶2抑制剂水平及眼轴长度的散点图

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Quantitative study of matrix metalloproteinases-2, tissue inhibitor of metalloproteinases-2 and soluble CD44 in aqueous humor of patients with high myopia and primary open angle glaucoma

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Quantitative study of matrix metalloproteinases-2, tissue inhibitor of metalloproteinases-2 and soluble CD44 in aqueous humor of patients with high myopia and primary open angle glaucoma