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[哌仑西平对雏鸡形觉剥夺性近视的影响及其可能机制]

[Effect of pirenzepine on form deprivation myopia in chicks and its possible mechanism].

作者信息

Dai Shu-zhen, Zeng Jun-wen, Wang Li-ya

机构信息

Ophthalmic Institute of Henan Province, Zhengzhou 450003, China.

出版信息

Zhonghua Yan Ke Za Zhi. 2006 Jan;42(1):42-7.

Abstract

OBJECTIVE

To observe the effect of M1-selective muscarinic antagonist, pirenzepine, on form deprivation myopia and investigate the expression of MMP-2 and its inhibitor TIMP-2 in the fibrous sclera in order to better understand the mechanism by which pirenzepine inhibits myopia.

METHODS

40 chicks after birth one day were divided into 4 groups randomly: I. Control group; II. Form deprivation group; III. Vehicle application group; IV. Pirenzepine injected group. Form deprivation myopia was established in right eyes of group II, III, IV by placement of a translucent occluder. The deprived eyes of group III and IV received daily subconjunctival administration of vehicle PBS and pirenzepine respectively. Optical measures such as refraction, axial length, equatorial diameter were made at the end of the experiment. Total RNA and protein were extracted from the posterior fibrous sclera chicks. The expression of MMP-2 and TIMP-2 mRNA and protein were investigated with RT-PCR and Western blot analysis respectively.

RESULTS

Refraction status, axial length, equatorial diameter of the eyes in pirenzepine injected group were significantly lower when compared with form deprivation group (P < 0.01), but the parameters were higher when compared with normal control group therefore relatively myopic changes were detected. There were no significant difference between drug control and pirenzepine injected group when optical measures and the expression of MMP-2, TIMP-2 were concerned (P > 0.05). The expressions (mRNA and protein) of both MMP-2 and TIMP-2 were significantly different in form deprivation group when compared with normal control group (MMP-2 mRNA increased by 143.51%, P < 0.01; protein increased by 114.60%, P < 0.01; TIMP-2 mRNA decreased by 55.05%, P < 0.01; protein decreased by 53.73%, P < 0.01). In pirenzepine injected group the relative expression of MMP-2 mRNA and protein were decreased obviously by 41.95% (P < 0.01) and by 36.16% (P < 0.01), while TIMP-2 mRNA and protein expression was increased significantly by 72.46% (P < 0.01) and by 53.05% (P < 0.01) respectively compared with the form deprived group.

CONCLUSION

Subconjunctivally administration of the M1 selective muscarinic antagonist, pirenzepine, partly prevents or restrains form deprivation induced myopia. It may exert its inhibitory effect by modulating the expression of MMP-2 and TIMP-2 in fibrous sclera.

摘要

目的

观察M1选择性毒蕈碱拮抗剂哌仑西平对形觉剥夺性近视的作用,并研究基质金属蛋白酶-2(MMP-2)及其抑制剂金属蛋白酶组织抑制因子-2(TIMP-2)在纤维性巩膜中的表达,以更好地理解哌仑西平抑制近视的机制。

方法

将40只出生1天的雏鸡随机分为4组:Ⅰ.对照组;Ⅱ.形觉剥夺组;Ⅲ.溶剂给药组;Ⅳ.哌仑西平注射组。通过放置半透明眼罩在Ⅱ、Ⅲ、Ⅳ组雏鸡的右眼建立形觉剥夺性近视。Ⅲ组和Ⅳ组的剥夺眼分别每日结膜下给予溶剂PBS和哌仑西平。实验结束时进行屈光、眼轴长度、赤道直径等光学测量。从雏鸡后段纤维性巩膜中提取总RNA和蛋白质。分别采用逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹法检测MMP-2和TIMP-2 mRNA及蛋白质的表达。

结果

与形觉剥夺组相比,哌仑西平注射组的眼屈光状态、眼轴长度、赤道直径明显降低(P<0.01),但与正常对照组相比这些参数较高,因此检测到相对近视性改变。在光学测量以及MMP-2、TIMP-2表达方面,溶剂对照组和哌仑西平注射组之间无显著差异(P>0.05)。与正常对照组相比,形觉剥夺组MMP-2和TIMP-2的表达(mRNA和蛋白质)均有显著差异(MMP-2 mRNA增加143.51%,P<0.01;蛋白质增加114.60%,P<0.01;TIMP-2 mRNA降低55.05%,P<0.01;蛋白质降低53.73%,P<0.01)。与形觉剥夺组相比,哌仑西平注射组MMP-2 mRNA和蛋白质的相对表达明显降低,分别降低41.95%(P<0.01)和36.16%(P<0.01),而TIMP-2 mRNA和蛋白质表达分别显著增加72.46%(P<0.01)和53.05%(P<0.01)。

结论

结膜下给予M1选择性毒蕈碱拮抗剂哌仑西平可部分预防或抑制形觉剥夺诱导的近视。它可能通过调节纤维性巩膜中MMP-2和TIMP-2的表达发挥其抑制作用。

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