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PPARy受体激动剂罗格列酮对形觉剥夺性近视和正常豚鼠屈光度的影响
引用本文:赵婧妍,李兵. PPARy受体激动剂罗格列酮对形觉剥夺性近视和正常豚鼠屈光度的影响[J]. 眼科新进展, 2022, 0(5): 347-352. DOI: 10.13389/j.cnki.rao.2022.0070
作者姓名:赵婧妍  李兵
作者单位:121000 辽宁省锦州市,锦州医科大学附属第一医院
摘    要:目的 探讨过氧化物酶体增殖物激活受体y(PPARy)激动剂罗格列酮在豚鼠形觉剥夺性近视(FDM)中的作用。方法 选取40只3周龄豚鼠(均为右眼),随机分成4组:正常组、FDM组、正常+罗格列酮组、FDM+罗格列酮组,其中正常组豚鼠不做处理,FDM组豚鼠使用头套法造模,正常+罗格列酮组豚鼠每天腹腔注射罗格列酮5 mg·kg-1,FDM+罗格列酮组豚鼠每天戴头套并腹腔注射罗格列酮5 mg·kg-1,持续28 d。实验前和实验后28 d测量豚鼠屈光度,实验后28 d测量豚鼠眼轴长度,保留眼球,免疫组织化学及Western blot测量豚鼠I型胶原蛋白(COL-I)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制剂-2(TIMP-2)蛋白的分布与表达,HE染色观察巩膜形态变化。结果 与正常组相比,FDM组豚鼠右眼屈光度和眼轴长度均增加,形成相对近视,差异均有统计学意义(均为P<0.05);巩膜明显变薄,胶原纤维排列紊乱,断裂明显,分布不规则。与正常组相比,正常+罗格列酮组豚鼠右眼屈光度和眼轴长度变化差异均无统计学意义(均为P>0.05);巩膜形态没有明显变化。与正常组相比,FDM+罗格列酮组豚鼠右眼屈光度和眼轴长度变化差异均无统计学意义(均为P>0.05)。与FDM组相比,FDM+罗格列酮组豚鼠右眼屈光度和眼轴长度均减少,差异均有统计学意义(均为P<0.05);巩膜胶原纤维排列松散,分布略紊乱。Western blot检测结果显示,与正常组相比,FDM组豚鼠巩膜中COL-I、TGF-β1、TIMP-2蛋白表达量均减少,MMP-2蛋白表达量增加,差异均有统计学意义(均为P<0.05);与正常组相比,正常+罗格列酮组豚鼠巩膜中,COL-I、TGF-β1蛋白表达量均增加,差异均有统计学意义(均为P<0.05),TIMP-2和MMP-2蛋白表达量差异均无统计学意义(均为P>0.05);与正常组相比,FDM+罗格列酮组豚鼠巩膜中COL-I蛋白的表达接近正常组,差异无统计学意义(P>0.05),TGF-β1、TIMP-2蛋白表达量均增加,MMP-2蛋白表达量减少,差异均有统计学意义(均为P<0.05);与FDM组相比,FDM+罗格列酮组豚鼠巩膜中COL-I、TGF-β1、TIMP-2蛋白表达量均增加,MMP-2蛋白表达量减少,差异均有统计学意义(均为P<0.05)。豚鼠巩膜中COL-I、TGF-β1、TIMP-2、MMP-2蛋白免疫组织化学表达趋势与Western blot检测结果一致。结论 PPARy受体激动剂罗格列酮可能通过调节TGF-β1、COL-I、TIMP-2和MMP-2蛋白的表达水平抑制FDM,对正常豚鼠的屈光影响不大。

关 键 词:PPARy  形觉剥夺性近视  豚鼠  罗格列酮

Effects of peroxisome proliferator-activated receptor y agonist rosiglitazone on diopter of guinea pigs with form-deprivation myopia and normal guinea pigs
ZHAO Jingyan,LI Bing. Effects of peroxisome proliferator-activated receptor y agonist rosiglitazone on diopter of guinea pigs with form-deprivation myopia and normal guinea pigs[J]. Recent Advances in Ophthalmology, 2022, 0(5): 347-352. DOI: 10.13389/j.cnki.rao.2022.0070
Authors:ZHAO Jingyan  LI Bing
Affiliation:The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,Liaoning Province,China
Abstract:Objective To investigate the role of peroxisome proliferator-activated receptor y (PPARy) agonist rosiglitazone in form-deprivation myopia (FDM) in guinea pigs. Methods Forty three-week-old guinea pigs (right eyes) were selected and randomly divided into four groups: normal group, FDM group, normal + rosiglitazone group, FDM + rosiglitazone group. Guinea pigs in the normal group received no treatment; guinea pigs in the FDM group were modeled using the headgear method; guinea pigs in the normal + rosiglitazone group were injected intraperitoneally with 5 mg·kg-1 of rosiglitazone once a day; guinea pigs in the FDM + rosiglitazone group wore headgear and were injected intraperitoneally with 5 mg·kg-1 of rosiglitazone for 28 days. The diopter was measured before the experiment and on the 28th day of the experiment, while the axial length (AL) was measured only on the 28th day of the experiment. The eyeballs were retained. The distribution and expression of Collagen I (COL-I), transforming growth factor β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase 2 (TIMP-2) were measured by immunohistochemistry and Western blot. The morphological changes of the sclera were observed by HE staining. Results Compared with the normal group, the diopter and AL of right eyes in the FDM group increased significantly (both P<0.05), resulting in relative myopia, the sclera was markedly thinned, and the collagen fibers were arranged disorderly, with obvious rupture and irregular distribution. Compared with the normal group, the changes in the diopter and AL of right eyes in the normal + rosiglitazone group were not statistically significant (both P>0.05), and there was no significant change in the sclera morphology. Compared with the normal group, there was no significant difference in the diopter and AL of right eyes in the FDM + rosiglitazone group (both P>0.05). Compared with the FDM group, the diopter and AL of right eyes in the FDM + rosiglitazone group were decreased significantly (both P<0.05), and the scleral collagen fibers were arranged loosely and disorderly. Western blot results showed that compared with the normal group, the expression levels of COL-I, TGF-β1 and TIMP-2 in the sclera of guinea pigs in the FDM group were decreased, while the expression level of MMP-2 was increased, and the differences were statistically significant (all P<0.05). Compared with the normal group, the expression levels of COL-I and TGF-β1 were significantly increased in the normal + rosiglitazone group (both P<0.05), while there were no significant differences in the expression levels of TIMP-2 and MMP-2 (both P>0.05). Compared with the normal group, the expression level of COL-I in the FDM + rosiglitazone group was close to that in the normal group (P>0.05), while the expression levels of TGF-β1 and TIMP-2 were increased, and the expression level of MMP-2 was decreased (all P<0.05). Compared with the FDM group, the expression levels of COL-I, TGF-β1 and TIMP-2 in the FDM + rosiglitazone group were increased, while the expression level of MMP-2 was decreased (all P<0.05).The immunohistochemical trend of COL-I, TGF-β1, TIMP-2 and MMP-2 in the sclera of guinea pigs was consistent with Western blot results. Conclusion The PPARy agonist rosiglitazone may inhibit FDM by regulating the expression levels of TGF-β1, COL-I, TIMP-2 and MMP-2, which has little effect on the diopter of normal guinea pigs.
Keywords:peroxisome proliferator-activated receptor y   form-deprivation myopia   guinea pig   rosiglitazone
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