|
3 讨论
以往的研究表明，视杆外节膜盘含有大量的磷脂［4］，磷脂的β位上有丰富的花生酸类的前体。磷脂酶A2(phospholipase a2,PLA2)可催化β键的断裂并释放出AA。AA经过环氧酶(cyclo-oxygenase)作用而产生前列腺素I2（prostaglandin I2，PGI2）和PGE2。PGI2的性质极不稳定，在短时间内转化成6-keto-PGF1α，所以6-keto-PGF1α可以间接反映PGI2的水平。本实验表明，光照后两组视网膜的PGE2和6-keto-PGF1α的含量均有增加，只是增加的程度不同。这种PG合成的增加可能是引起视网膜自由基含量升高的因素之一。另有实验发现，光照后6小时视网膜蛋白激酶C(protein kinase C,PKC)的活性升高［3］，与此同时出现的PGE2与6-keto-PGF1α含量增加可能有一定的关系。因为PKC的激活有Ca2＋的增加，后者可激活PLA2。近期的研究表明，PKC通过对lipocortin(脂调素或脂皮素)的磷酸化，使其丧失对PLA2的抑制作用，从而引起PG的合成增加［5］。视网膜光化学损伤中AA代谢明显增强所产生的自由基以及AA衍生物的扩张血管和吞噬细胞趋化作用，在诱发或加重视网膜光化学损伤过程中起到一定的作用。
视网膜光性损伤的药物防治研究，大多是从抗氧化和清除自由基两条路径考虑，如用维生素 e等。此外，flunarizine和皮质类固醇也被同类实验采用，前者可降低Ca2＋的水平，而后者的作用认为是与稳定细胞膜有关［6-9］。虽然在解释上述药物的疗效时，大部分作者并未提及对PG合成的影响，但事实上维生素 e及其它酚类抗氧化剂均能抑制AA的过氧化反应；flunarizine可阻滞Ca2＋水平升高，影响PLA2的活性；皮质类固醇是目前最佳的AA代谢抑制剂，它可诱导lipocortin的合成，lipocortin与PLA2结合使其丧失激发AA代谢的能力。本实验结果显示，DXM组在光照后6小时和1，3天视网膜的PGE2和6-keto-PGF1α含量明显低于对照组，表明DXM可抑制视网膜光化学损伤中AA的代谢过程，对于7，14天该组2种PG水平升高，可能与DXM的用药期和半衰期较短有关。通过阻止PG的生成，DXM可能对视网膜光化学损伤起到防护作用。
表1 大鼠视网膜6-keto-PGF1α的含量( ±s)(pg/mg)
Tab． 1 levels of the 6-keto-PGF1α in rat retina (±s)(pg/mg)
| Groups |
Before
light exposure |
After light exposure |
| 6h |
1d |
3d |
7d |
14d |
| Control |
1.96±0.30 |
4.68±0.69* |
7.50±0.57* |
10.40±0.71* |
8.88±0.99* |
3.69±0.77* |
| DXM |
2.10±0.40 |
2.50±0.59▲ |
4.68±0.81+▲ |
6.87±1.10+▲ |
8.41±0.95+ |
4.29±0.58+ |
* Significantly different(P＜0.01) from the control group before light exposure. + Significantly different(P＜0.01) from the DXM group before light exposure. ▲ Significant differences(P＜0.01) between DXM and Control groups at same time
表2 大鼠视网膜PGE2的含量(±s)(pg/mg)
Tab． 2 levels of the PGE2 in rat retina (±s)(pg/mg)
| Groups |
Before
light exposure |
After light exposure |
| 6h |
1d |
3d |
7d |
14d |
| Control |
13.33±1.93 |
37.50±2.75* |
48.06±4.04* |
81.90±4.89* |
68.26±3.85* |
34.94±4.23* |
| DXM |
11.45±1.90 |
20.60±4.28+▲ |
37.36±3.34+▲ |
54.85±4．57+▲ |
70.08±3.57+ |
38.51±2.85+ |
* Significantly different(P＜0.01) from the control group before light exposure. + Significantly different(P＜0.01) from the DXM group before light exposure. ▲ Significant differences(P＜0.01) between DXM and Control groups at same time
本课题受国家自然科学基金资助，基金号39170768
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(收稿：1998-11-25 修回：1999-01-10) 上一页 [1] [2] |
