假鳞皮样脱皮综合征患者房水中基质金属蛋白酶-1组织抑制因子和结缔组织生长因子水平升高

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目的最近发现假鳞皮样脱皮综合征(pseudoexfoliationsyndrome,PXF)患者房水中转化生长因子β1(transforminggrowthfactorβ1,TGFβ1)表达增高,因为抗TGFβ1可潜在的干扰前房相关免疫偏离的维持,针对抗TGFβ1治疗的关注日益增高,作者探究了前房中基质金属蛋白酶1组织抑制因子(tissueinhibitorofmatrixmetalloproteinase1,TIMP1)、基质金属蛋白酶9(matrixmetalloproteinase9,MMP9)和结缔组织生长因子(connectivetissuegrowthfactor,CTGF)的水平,以测定他们是否可以作为选择性治疗目标。方法从施行常规白内障手术患者中收集房水样本。全部患者分为3组:PXF组、色素膜炎组和对照组。根据活组织显微镜检查观察到的表皮脱落物质密度及青光眼的有无,PXF组进一步分为3组。通过酶联免疫吸附测定法(ELISA)测定TIMP1,MMP9和CTGF的水平。结果与对照组(n=112,5.73(0.43)ng/ml)相比,PXF组前房TIMP1具有显著高密度(n=56,mean(SE),9.76(1.10)ng/mL,P<0.01);同样,前房CTGF水平PXF眼(n=36,4.38(0.65)ng/mL)明显高于对照眼(n=29,2.35(0.46)ng/mL,P<0.05)。而且,伴青光眼PXF组CTGF水平明显高于不伴青光眼PXF组(6.03(1.09)ng/mlv2.73(0.45)ng/ml,P<0.01)。PXF组和对照组中MMP9水平低于检测限度,2组之间无统计学差异。结论PXF眼前房高水平TIMP1和低水平MMP9说明蛋白水解活性的下调。CTGF浓度的增长说明PXF病理学上的纤维变性。MMP/TIMP表达的调整和抗CTGF治疗可以提供一条控制PXF及其视觉疾病发病率的途径。 Purpose Recently, the expression of transforming growth factor β1 (TGFβ1) in aqueous humor has been found to be elevated in patients with pseudoexfolial syndrome (PXF) because anti-TGFβ1 potentially interferes with the maintenance of anterior chamber-related immune bias and is resistant to treatment with TGFβ1 With increasing attention, the authors explored the levels of tissue inhibitor of matrix metalloproteinase 1 (TIMP1), matrix metalloproteinase 9 (MMP9) and connective tissue growth factor (CTGF) in the anterior chamber to determine if they could As a selective treatment target. Methods Aqueous humor samples were collected from patients undergoing conventional cataract surgery. All patients were divided into 3 groups: PXF group, pigmentary inflammation group and control group. The PXF group was further divided into three groups according to the density of the exfoliative material and the presence or absence of glaucoma observed by the biomicroscopy. The levels of TIMP1, MMP9 and CTGF were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group, TIMP1 in the anterior chamber of PXF group was significantly higher (n = 56, mean (SE), 9.76 (1.10) ng / mL, P <0.01 Similarly, CTGF levels in the anterior chamber were significantly higher in the PXF eyes (n = 36, 4.38 (0.65) ng / mL) than those in the control eyes (n = 29,2.35 (0.46) ng / mL, P <0.05). Moreover, CTGF levels in patients with glaucoma PXF were significantly higher than those in patients without glaucoma PXF (6.03 (1.09) ng / mlv 2.73 (0.45) ng / ml, P <0.01). The level of MMP9 in PXF group and control group was lower than the detection limit, and there was no significant difference between the two groups. Conclusions High PXP anterior chamber tissue level of TIMP1 and low level of MMP9 indicate a decrease in proteolytic activity. The increase in CTGF concentration indicates fibrotic pathology in PXF. Adjustment of MMP / TIMP expression and anti-CTGF therapy may provide a way to control the incidence of PXF and its visual disease.
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