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亚洲国家儿童和青少年近视罹患率逐年攀升,严重影响到身心健康,并且随着近视程度的加深,还可能出现不可逆的眼底改变,严重时可致盲[1-2]。阿托品是治疗近视的首选药物,广泛运用于临床。1%阿托品临床疗效确切,能有效预防和治疗近视,然而畏光、刺激、干眼等副反应发生率较高,多数患者长期使用时难以耐受[3-7]。多项临床研究对不同浓度阿托品的治疗作用及副作用深入观察,发现0.01%阿托品治疗近视时副作用明显低于1%阿托品,且停药后的反弹现象发生率也显著降低,但在近视快速进展期的控制效果却不及1%阿托品[8-11]。
因此,积极探索合理的治疗方案,在降低阿托品用量的同时保证其治疗效果成为近视治疗的关键和难点。本研究采用豚鼠近视模型观察比较优化方案(交替使用1%、0.01%阿托品)与单一浓度方案在近视控制效果上的差异。
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空白对照组(图1A、2A)实验前后双眼屈光度和眼轴差异均无统计学意义(P>0.05)。生理盐水组(图1 B)屈光度和眼轴长度在1周末时为(0.88±1.21)D和(7.56±0.10)mm,与实验前(3.68±1.12)D和(7.38±0.09)mm相比有显著性差异(P<0.01),2周末时该组出现绝对近视(−0.33±1.41)D和(7.62±0.08 mm),4周末时屈光度和眼轴持续呈近视化改变(−1±2.47)D和(7.74±0.09)mm。给药各组模型眼屈光度、眼轴长度均有不同程度近视化改变。各干预组对照眼的屈光度、眼轴长度于实验前后均无显著差异(P>0.05)。以上结果说明豚鼠近视模型建立取得成功。
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空白对照组(图1A)双眼屈光度于实验前后均无统计学差异(P>0.05);生理盐水组(图1B)模型眼屈光度迅速下降,每周测量数值均与实验前有显著差异(P<0.01);1%阿托品组(图1C)模型眼屈光度呈下降趋势,于第3、第4周末时分别降至(1.75±0.69)D和(1.38±1.15)D,均与实验前(3.50±1.14)D有显著差异(P<0.05);0.01%阿托品组(图1D)模型眼屈光度快速下降,在第1周末时与实验前相比即存在显著性差异[(1.32±1.15)D 对(2.82±1.35)D, P<0.01],4周末时出现绝对近视(−0.64±0.20)D;优化组1(图1E)模型眼屈光度缓慢下降,第4周末时的屈光度值为(0.95±1.90)D,与实验前[(3.55±1.85)D]相比有统计学差异(P<0.01),该组抑制屈光度下降结果低于1%阿托品组,但高于0.01%阿托品组。优化组2(图1F)模型眼实验前2周快速下降,第2周末时的屈光度(0.79±0.93)D与实验前(2.93±1.42)D相比有显著性差异(P<0.01);该组第3周换用1%阿托品后,屈光度回升至(2.10±1.00)D,与第2周末的屈光度值有显著性差异(P<0.01);第4周末时屈光度值下降至(1.36±1.61)D,与实验前无统计学差异(P>0.05)。各组对照眼实验前后屈光度无统计学差异(P>0.05)。
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空白对照组(图2A)双眼眼轴长度于实验前后均无统计学差异(P>0.05);生理盐水组(图2B)模型眼眼轴迅速延长,每周测量数值均与实验前有显著差异(P<0.01);1%阿托品组(图2C)模型眼眼轴长度于实验前后均无统计学差异(P>0.05);0.01%阿托品组(图2D)模型眼于实验1周时出现了明显的眼轴延长(7.47±0.08)mm对(7.37±0.06)mm,于第4周末时该组眼轴延长至(7.62±0.08)mm,均与实验前有显著差异(P<0.05);优化组1(图2E)模型眼造模前眼轴长度为(7.39±0.05)mm,于第2周末时眼轴长度明显延长(7.52±0.05)mm,P<0.05,第3、4周使用0.01%阿托品治疗后,2周内眼轴延长速度有所减缓[(7.54±0.04)mm和(7.59±0.03)mm];优化组2(图2F)模型眼眼轴在实验前2周迅速延长,造模前眼轴长度为(7.37±0.07)mm,实验1周时出现了明显的眼轴延长[(7.50±0.07)mm, P<0.01],第3、4周使用1%阿托品治疗后眼轴长度为(7.54±0.06)mm和(7.56±0.05)mm,与第2周末相比差异无统计学意义(P>0.05)。各组对照眼实验前后眼轴长度无统计学差异(P>0.05)。
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OCTA结果提示,空白对照组脉络膜结构完整,边界清晰。干预组模型眼脉络膜均出现不同程度的结构和形态的改变,如组织厚度下降,边界模糊等(图3)。OCTA结果可见各干预组脉络膜厚度差别较为明显,大小依次为:1%阿托品组>优化组2>优化组1> 0.01%阿托品组>生理盐水组(表1)。
表 1 各组模型眼脉络膜厚度
组别 脉络膜厚度(l/μm) 空白对照组 72.25±3.30**## 生理盐水组 33.60±2.19 1%阿托品组 57.00±1.73 0.01%阿托品组 41.00±4.08**## 优化组1 48.67±0.58**## 优化组2 51.33±2.52**# * P<0.05、** P<0.01,与空白对照组比较; # P<0.05、## P<0.01,与1%阿托品组比较 -
HE染色结果提示,空白对照组巩膜组织胶原纤维排列整齐、分布均匀、连接致密。各干预组模型眼的巩膜存在不同程度的组织结构改变,如组织厚度变薄、胶原纤维粗细不均、排列稍紊乱、组织间隙变大等(图4)。HE染色可见各组巩膜厚度的差别较明显,空白对照组巩膜厚度为(91.03±1.68)μm,各干预组豚鼠模型眼的巩膜厚度均小于空白对照组,厚度大小依次为:1%阿托品组>优化组2 >优化组1> 0.01%阿托品组>生理盐水组(表2)。
表 2 各组模型眼巩膜厚度
组别 巩膜厚度(l/μm) 空白对照组 91.03±1.68**## 生理盐水组 39.17±2.15 1%阿托品组 74.4±1.95** 0.01%阿托品组 54±2.99**## 优化组1 63.43±2.10**## 优化组2 67.40±2.79**# * P<0.05,** P<0.01,与空白对照组比较; # P<0.05,## P<0.01,与1%阿托品组比较。
Study on the effect of optimized dosing regimen of atropine on the treatment of myopia in guinea pigs
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摘要:
目的 研究优化的阿托品给药方案对豚鼠近视的治疗作用。 方法 从46只21 d龄豚鼠中随机选取6只作为空白对照,其余40只随机分为5个干预组:1%阿托品组、0.01%阿托品组、优化组1、优化组2及生理盐水组。随机选择干预组豚鼠单眼作为模型眼并予形觉剥夺,对侧眼为自身对照,干预时间均为4周。于实验前及每周末测量豚鼠双眼屈光度、眼轴数据,实验结束后行脉络膜和巩膜测量。 结果 0.01%阿托品组模型眼屈光度迅速下降,实验前后有显著差异[(2.82±1.35)D对(−0.64± 0.20)D, P<0.01]。1%阿托品组、优化组1模型眼屈光度下降,实验前后均有统计学差异[(3.50±1.14)D 对(1.38±1.15)D, P<0.05;(3.55±1.85)D 对(0.95±1.90)D, P<0.01]。优化组2模型眼屈光度下降,实验前后无统计学差异[(1.36±1.61)D 对(2.93±1.42)D, P>0.05)]。形觉剥夺后,1%阿托品组眼轴长度无显著变化(P>0.05),其余各干预组眼轴均有不同程度延长。1%阿托品组、优化组2、优化组1脉络膜和巩膜的厚度大于 0.01%阿托品组。 结论 两种优化给药方案的抑制形觉剥夺豚鼠近视作用优于0.01%阿托品,与1%阿托品效果相近。 Abstract:Objective To study the effect of optimized atropine administration regimen on myopia in guinea pigs. Methods Forty six 21-day old guinea pigs were used for this study. Six were randomly selected as blank control, and the remaining 40 were randomly divided into 5 intervention groups: 1% atropine group, 0.01% atropine group, optimized group 1, optimized group 2, and saline group. One eye of the guinea pig in the intervention groups was randomly selected as the model eye and given form deprivation, and the contralateral eye was the self-control. The duration of intervention was 4 weeks. The diopter and axial length of guinea pig eyes were measured before the experiment and at each weekend. Choroid and sclera were measured after the experiment. Results The diopter of the model eyes in the 0.01% atropine group decreased rapidly. There was a significant difference before and after the experiment [(2.82±1.35)D vs (−0.64±0.20)D, P<0.01]. The diopter of model eyes decreased in 1% atropine group and optimized group 1, and the difference was statistically significant [(3. 50±1.14)D vs (1.38±1.15)D, P<0.05; (3.55±1.85)D vs (0.95±1.90)D, P<0.01]. In optimized group 2, the diopter of model eyes decreased, and there was no significant difference before and after the experiment [(1.36±1.61)D vs (2.93±1.42)D, P>0.05). After form deprivation, the axial length in 1% atropine group did not change significantly (P>0.05). The axial length in other intervention groups was extended to varying degrees. The thickness of choroid and sclera in 1% atropine group, optimized group 1 and optimized group 2 were greater than that in 0.01% atropine group. Conclusion The two optimized dosing regimens worked better than 0.01% atropine in inhibiting myopia in guinea pigs with form deprivation, and were similar to 1% atropine. -
Key words:
- myopia /
- atropine /
- form deprivation /
- guinea pigs
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表 1 各组模型眼脉络膜厚度
组别 脉络膜厚度(l/μm) 空白对照组 72.25±3.30**## 生理盐水组 33.60±2.19 1%阿托品组 57.00±1.73 0.01%阿托品组 41.00±4.08**## 优化组1 48.67±0.58**## 优化组2 51.33±2.52**# * P<0.05、** P<0.01,与空白对照组比较; # P<0.05、## P<0.01,与1%阿托品组比较 表 2 各组模型眼巩膜厚度
组别 巩膜厚度(l/μm) 空白对照组 91.03±1.68**## 生理盐水组 39.17±2.15 1%阿托品组 74.4±1.95** 0.01%阿托品组 54±2.99**## 优化组1 63.43±2.10**## 优化组2 67.40±2.79**# * P<0.05,** P<0.01,与空白对照组比较; # P<0.05,## P<0.01,与1%阿托品组比较。 -
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