哌仑西平影响豚鼠实验性近视眼的研究

目的 探讨玻璃体腔注射选择性M_1受体拮抗剂哌仑西平对豚鼠形觉剥夺性近视眼视网膜、脉络膜、巩膜和虹膜-睫状体组织中M_1和M_4受体mRNA表达的影响.方法 采用随机分组设计的实验研究.1～2周龄的三色豚鼠24只,随机分为4组:正常对照组(N)6只,单纯形觉剥夺组(FDM)6只,药物对照组(S)6只,哌仑西平组(P)6只,均以左眼为实验眼,P组隔日玻璃体腔注射500μg哌仑西平;S组隔日玻璃体腔注射生理盐水.21 d后结束实验.提取各组眼视网膜、脉络膜、巩膜和虹膜-睫状体组织总RNA,半定量RT-PCR检测M_1和M_4亚型mRNA表达变化.3组间数据的比较采用单因素方差分析和Tukey post hoc检验.结果 21d时,FDM与N组相比较,FDM组眼轴相对延长0.29mm,产生相对近视-4.92 D,差异有统计学意义(P<0.001).P组与S组相比较,眼轴相对减少了0.30 mm,产生+0.88 D的相对远视,差异均有统计学意义(P<0.001).S组与FDM之间屈光度数的差异无统计学意义;而眼轴变化有统计学意义(S组相对延长0.08 mm,而FDM组相对延长0.29/mm).半定量PCR结果显示:P组与S组相比较,其视网膜、脉络膜和虹膜睫状体组织M_1和M_4亚型mRNA的表达差异无统计学意义(P>0.05).而在后极部巩膜组织,M_1和M_4亚型mRNA的表达较药物对照组显著性增加(P<0.05),其中M_1受体表达增加19.16%,M_4受体表达增加64.29%.结论 哌仑西平能够有效抑制豚鼠形觉剥夺近视的发展.巩膜组织M_1和M_4亚型及其胆碱能通路可能参与M受体拮抗剂抑制近视发展.

Effect on of pirenzepine on expression of mAChRs in the ocular tissues of guinea pig with form-deprived myopia

Objective To study effects of vitreous injecting M_1-selective muscarinic antagonist,pirenzepine,on expression of M_1 and M_4 receptor in retina,choroid,schera and iris-ciliary body of guinea pig with form-deprived myopia.Methods Twenty-four 1-2 week-old pigmented guinea pigs were randomly divided into four groups.Groupl:normal control (N) (n=6);group 2:simple form-deprived myopia (FDM)(n=6);group 3:drug control (S) (n=6);group 4:pirenzepine(P) (n=6).Expression changes of M_1 and M_4 muscarinic receptors at mRNA level were detected by semi-quantitative RT-PCR in retina,choroid,sclera and iris-ciliary body.Result 1.After 21 days'treatment,FDM group produced relative myopia of -4.92 D and an axial length of 0.29 mm with significance(P<0.001),compared with N group.Compared with group S,the relative refractive error in group P wag+0.88 D,and axial length decreased 0.30 mm with respectively significance(P<0.001).Differences in refractive error between grouP S and group FDM were not significant,but in axial length were significant(0.08mm vs.0.29mm)(P<0.05).2.Semi-quantitative RT-PCR:M_1 and M_4 mRNA expression showed no significant differences in the retina,choroid and iris-ciliary body of group P compared with group S(P>0.05).Of interest,in the posterior sclera,mRNA expression of group P was significantly greater than that of group S for the M_1(P< 0.05)and M_4 subtypes(P<0.05).The M_1 and M_4 subtype in group P was increased by +19.16%and +64.29% respectively. Conclusion M_1-selective muscarinic antagonist,pirenzepine,can effectively inhibit form-deprived myopia in guinea pig. M_1 and M_4 subtype in sclera and their cholinergic signaling may participate in muscarinic antagonist inhibition of myopic development.