倍他洛尔与氨基胍对大鼠视网膜缺血再灌注损伤的保护作用

目的:通过观察在大鼠急性高眼压模型中视网膜一氧化氮合成酶(nitric oxide synthase,NOS)分布及含量的变化,并检测视网膜丙二醛(malondialdehyde,MDA)水平的变化,探讨氨基胍(aminoguanidine,AG)与倍他洛尔(betaxolol)对大鼠高眼压视网膜缺血再灌注损伤的保护作用。方法:采用前房穿刺加压法建立大鼠缺血再灌注损伤模型,维持灌注时间60min。将各组右眼球经视神经矢状切片标本做HE染色进行视网膜组织学观察,还原型尼克酰胺嘌呤二核苷酸磷酸-黄递酶(NADPH-d)法检测视网膜NOS染色阳性的细胞数,硫代巴比妥酸(thiobarbituric acid,TBA)法测定各组左眼球视网膜MDA含量。结果:各组视网膜均有NOS表达,NOS阳性细胞在视网膜主要分布于视网膜节细胞层(ganglion cell layer,GCL)、内丛状层(inner plexiform layer,IPL)、内核层(inner nuclearlayer,INL),200倍视野计数生理盐水组视网膜GCL的NOS阳性细胞数明显高于空白对照组(P<0.01);AG与betaxolol药物治疗各组的NOS阳性细胞数较生理盐水组减少(P<0.05);视网膜NOS阳性细胞数与视网膜MDA含量增减呈正相关性(r=0.69,P<0.01)。结论:AG通过对诱导型NOS的抑制在大鼠高眼压诱导视网膜损伤中起到视神经保护作用。betaxolol通过抑制钙通道,使NO的生成减少,增加抗氧化能力,从而起神经保护作用。

Protective effect of aminoguanidine and betaxolol on retinal ischemia-reperfusion injury in rats

AIM:To observe the nitric oxide synthase(NOS) expression and measure the level of malondialdehyde(MDA) and to investigate the neuroprotective effect of NOS inhibitor aminoguanidine(AG) and betaxolol on rat retinal tissues in acute intraocular hypertension.METHODS:The ischemia-reperfusion injury models were established in 24 SD rats by increasing intraocular pressure through anterior chamber infusion.Three of 27 SD rats were randomly selected as blank controls.With intraocular hypertension persisting for 60 minutes,these 24 rats were subdivided into four groups:normal saline group,betaxolol treated group(2.5g/L),AG treated group(100mg/kg),and betaxolol AG combined treatment group.Sagittal sections of optic nerves of right eyeballs were performed HE staining and retinal histology was observed at different time points after treatment.The NADPH-diaphorase reaction was employed to identify the NOS positive expression in the retina,and the contents of MDA were measured by TBA spectrophotometry.RESULTS:The expressions of NOS were localized in retinas of all groups.In the retina,NOS positive cells mainly distributed in the retinal ganglion cell layer(GCL),inner plexiform layer(IPL) and inner nuclear layer(INL).The count of NOS positive cells in normal saline group was significantly more than that of the blank control group in retinal GCL(P<0.01),while the number of NOS positive cells in AG,betaxolol treatment groups was less than that of normal saline group(P<0.05).Moreover,the count of retinal NOS positive cells was positively correlated with the content of retinal MDA(r=0.69,P<0.01).CONCLUSION:By inhibiting the activity of iNOS,AG might protect the retina against acute ocular hyperten-sion injury.In addition,betaxolol plays a role of neuroprotection by reducing intracellular overfreight of Ca2 ,inhibiting the production of NO and enhancing the ability of anti-oxidation in retina.