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14 d。同时每日腹腔注射1 mL对应剂量的药物。14 d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)/m^(2)刺激光下b波、明视ERG 3.0(cd·s)/m^(2)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 lx,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 CheKine TM 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)/m^(2) stimulated light,b-wave in bright-vision ERG 3.0(cd·s)/m^(2) 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.
作者
程天豪
邹玉平
简柳连
章梦一
豆艺璇
Cheng Tianhao;Zou Yuping;Jian Liulian;Zhang Mengyi;Dou Yixuan(Graduate School,Guangzhou University of Traditional Chinese Medicine,Guangzhou 510006,Guangdong province,China;Department of Ophthalmology,General Hospital of the Southern Theater of Operations of the Chinese People s Liberation Army,Guangzhou 510010,Guangdong Province,China)
出处
《国际眼科杂志》
2024年第2期196-202,共7页
International Eye Science
基金
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)。