褪黑素受体激动剂(Neu-P11)对兔眼压降低的实验研究

Experimental study on the effect of melatonin receptor agonist( Neu- P11 ) in reduce the intraocular pressure in normotensive rabbit

目的观察褪黑素受体激动剂(Neu-P11)对眼压的影响以及水通道蛋白1在正常眼压兔眼组织中的表达。方法新西兰兔30只随机分为对照组、褪黑素组和Neu-P11组。用局部点眼法,1个月后处死动物,取眼前段组织;用免疫组化法、RT-PCR法和Western blot法检测。结果 50μmol·L-1Neu-P11点眼,可使兔眼压降低,1 h达到最低(P<0.01)。Neu-P11组和褪黑素组,角膜内皮、虹膜基质血管和色素上皮细胞、睫状体非色素上皮以及小梁网组织细胞的胞膜和胞浆均可见阳性表达,且阳性反应数明显增多。Neu-P11组和褪黑素组AQP1mRNA和蛋白质水平较对照组上调,且Neu-P11组比褪黑素组更高,2组差异有统计学意义(P<0.05)。结论 Neu-P11能够降低兔眼压,并能够使兔眼组织中AQP1的表达增高。

Objective To investigate the effect of melatonin receptor ag- onist （Neu- P11 ）on intraocular pressure （IOP） and the expression of aquaporin 1 （AQP1） in normal lOP rabbit ocular tissues. Methods Total of the 30 male New Zealand white rabbits were divided into control group （ with saline ）, melatonin group （ 50 μmol·L-1 ） and Neu - P11 group（50μmol·L-1）. IOP was measured for 7 hours by means of a Tonopen XL contact tonometer. The tissue blocks of the anterior half of the rabbit globes were cut according to a standard protocol, includes the cornea, iris, ciliary body, angle and anterior sclera tissues after one month. The expression of AQPlwere detected in different tissues by immunohistochernistry. The level of AQP1 in the rabbit ocular tissue were measured by RT - PCR and Western blot. Results When the dose at 50μmol·L-1, there was a more significant decline in IOP at 1 hour in Neu - Pll group compared with the control group （P 〈0. 01 ）, and there was a most longest duration in IOP recovery in Neu -P11 group. The expression of AQP1 only distributes m the cytoplasm of non - pigmented epithelial cells of ciliary body and trabeeular meshwork cells in the control group. However, in the Nue- P11 and melatonin groups, there was a significant positive expression of AQP1 in the cytoplasm of corneal endothelial cell, iris stromal vascular endothelial cells and pigment epithelial cells, in addition non - pigmented epithelial cells of ciliary body and trabecular meshwork cells. Considerably increased expression was displayed in Nue - pl 1 group compared with the melatonin group. （P 〈 0. 05 ）. Conclusion Neu -P11 could reduce intraocular pressure and increase expression of AQP1 in rabbits.