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硫辛酸烟酸二联体对蓝光致大鼠视网膜损伤的防治作用OACSTPCD

Prevention and treatment of lipoic acid-niacin on blue-light-induced retinal damage in rats

中文摘要英文摘要

目的:探讨硫辛酸烟酸二联体(N2L)对蓝光致SD大鼠视网膜损伤的防治作用及最佳药物剂量,探寻其可能存在的保护机制. 方法:选取150-200 g的SPF级雄性SD大鼠36只,随机分为正常对照组、蓝光损伤组、N2L低剂量组(1.0 mg/kg)、N2L中剂量组(2.5 mg/kg)、N2L高剂量组(5.0 mg/kg)及生理盐水组,每组各6只.正常对照组12 h明暗循环饲养,其余组每日接受9 h日常光照,3 h波长455 nm、强度3000±50 lx蓝光照射及12 h黑夜来建立损伤模型,持续14d.同时每日腹腔注射1 mL对应剂量的药物.14d后,所有组常规12 h明暗循环再饲养5 d,采用视网膜电图检查.过量麻醉法处死大鼠制备标本,HE染色,在光学显微镜下观察外核层厚度;CheKineTM超氧化物歧化酶(SOD)活性检测试剂盒检测SOD活性;Western Blot检测大鼠视网膜Caspase-3、醌氧化还原酶1(NQO1)、谷胱甘肽巯基转移酶(GST)、Bcl-2和Bax蛋白表达量. 结果:蓝光损伤组暗视ERG 3.0、10.0(cd·s)/m2刺激光下b波、明视ERG 3.0(cd·s)/m2刺激光下b波振幅及震荡电位第2个波峰振幅显著低于正常对照组(均P<0.01),N2L中剂量组较蓝光损伤组振幅显著提高(均P<0.05),且与正常对照组无显著差异;蓝光损伤组较正常对照组视网膜ONL厚度下降(P<0.001),N2L中剂量组厚于蓝光损伤组(P<0.001),与正常对照组无显著差异;N2L中剂量组超氧化物歧化酶活性显著高于其余5组(P<0.05);蓝光损伤组Caspase-3、Bax及NQO1表达量较正常对照组更高(均P<0.01),N2L中剂量组Bax、Caspase-3表达量较蓝光损伤组显著降低(均P<0.001),而GST、NQO1及Bcl-2显著增加(均P<0.01). 结论:2.5 mg/kg N2L能有效拮抗蓝光对SD大鼠视网膜的损伤作用,有望成为其防治药物.

·AIM:To investigate the preventive effect and optimal drug dose of lipoic acid-niacin(N2L)against blue light-induced retinal damage in SD rats,and to explore its possible protective mechanism. ·METHODS:A total of 36 specific pathogen free-grade male SD rats of 150-200 g were selected and randomly divided into normal control group,blue light injury group,N2L low-dose group(1.0 mg/kg),N2L medium-dose group(2.5 mg/kg),N2L high-dose group(5.0 mg/kg),and physiological saline group,with 6 rats in each group.The normal control group was reared in a 12 h dark and light cycle,and the rest of the groups received 9 h of daily light exposure,3 h of blue light irradiation with a wavelength of 455 nm and an intensity of 3000±50 Ix,and 12 h of darkness to establish the injury model,and were exposed to light exposure for 14 d.For 14 consecutive durations,a 1 mL dose of the corresponding drug was injected intraperitoneally.The rats were reared for another 5 d with a regular 12 h light-dark cycle and were examined by electroretinography.Specimens were prepared by over anesthesia,HE staining,and the thickness of the outer nuclear layer was observed under a optical microscope;superoxide dismutases(SOD)activity was detected by CheKineTM SOD Activity Assay Kit;and the retinal Caspase-3,quinone oxidoreductase 1(NQO1),glutathione S transferase(GST),Bcl-2,and Bax protein expression in rat retina were detected by Western blot. ·RESULTS:The amplitude of b-wave in dark-vision ERG 3.0 and 10.0(cd·s)/m2 stimulated light,b-wave in bright-vision ERG 3.0(cd.s)/m2 stimulated light,and the amplitude of the 2nd wave peak of oscillatory potential were significantly lower in blue light injury group than that in the normal control group(all P<0.01),while the amplitude was significantly higher in the N2L medium-dose group than in the blue light injury group(all P<0.05),and was not statistically different from that of the normal control group;the thickness of the retina in the blue light injury group was decreased in the ONL compared with that of the normal control group(P<0.001),while in the N2L medium dose group,it was thicker than that of the blue light injury group(P<0.001),and there was no statistically significant difference from the normal control group;SOD activity was significantly higher in the N2L medium-dose group than in the remaining 5 groups(P<0.05);the expression of Caspase-3.Bax,and NQO1 in the blue light injury group was higher than that of the normal control group(all P<0.01),and expression of Bax and Caspase-3 was significantly lower in the N2L medium-dose group compared with the blue light injury group(all P<0.001),whereas GST,NQO1 and Bcl-2 were significantly increased(all P<0.01). ·CONCLUSION:A concentration of 2.5 mg/kg N2L can effectively antagonize the damaging effect of blue light on the retina of SD rats,and it is expected to be a preventive and curative drug for it.

程天豪;邹玉平;简柳连;章梦一;豆艺璇

(510006)中国广东省广州市,广州中医药大学研究生院||(510010)中国广东省广州市,中国人民解放军南部战区总医院眼科(510010)中国广东省广州市,中国人民解放军南部战区总医院眼科

蓝光SD大鼠硫辛酸烟酸二联体(N2L)氧化损伤视网膜

blue lightSD ratlipoic acid-niacin(N2L)oxidative damageretina

《国际眼科杂志》 2024 (002)

196-202 / 7

广东省自然科学基金(No.2019A1515011732);广州市科学技术局资助项目(No.202002030413)Guangdong Provincial Natural Science Foundation(No.2019A1515011732);Funded Project of Guangzhou Science and Technology Bureau(No.202002030413)

10.3980/j.issn.1672-5123.2024.2.04

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