热休克蛋白反应对青光眼模型大鼠RGCs中HSP72生成的影响及其作用机制研究

Effect of HSP response on HSP72 production in RGCs of glaucoma model rats and its mechanism

目的研究热休克蛋白(HSP)反应对青光眼模型大鼠视网膜神经节细胞(RGCs)中热休克蛋白72(HSP72)生成的影响及其作用机制。方法取64只Wistar大鼠,随机分为正常对照组(正常大鼠)、模型组(青光眼模型)、实验1组(青光眼+腹腔注射硫酸锌)、实验2组(青光眼+热休克反应干预),每周各16只,各组进行相应处理。除正常对照组外,其余三组大鼠右眼均行激光光凝处理,比较大鼠激光处理前后左、右眼的眼压变化;比较各组大鼠实验后不同时间点RGCs平均密度和RGCs中的HSP72抗体水平。结果各组青光眼大鼠激光处理前后左眼眼压的组内和组间比较,均无显著差异(P>0.05);模型组、实验1组和实验2组经激光处理后3 d、1周、2周、4周右眼的眼压均明显高于激光处理前(P<0.05),而组间比较并无显著差异(P>0.05)。正常对照组实验后不同时间点RGCs中均未见HSP72抗体表达;模型组在激光光凝后2周、4周亦未见HSP72抗体表达;实验1组和实验2组在激光处理后3 d至2周时HSP72抗体水平逐渐升高,到2周时达到高峰,随后有所降低至接近正常水平;实验2组不同时间点HSP72抗体水平较模型组显著升高,较实验1组显著下降(P<0.05)。相比正常对照组,模型组、实验1组和实验2组经激光处理后3d、1周、2周、4周RGCs平均密度均显著下降(P<0.05);实验2组不同时间点RGCs平均密度较模型组和实验1组均显著升高(P<0.05)。结论在青光眼大鼠模型中,通过HSP反应干预可刺激HSP72在RGCs中的生成,且具有保护大鼠RGCs和视神经功能的作用。

Objective To study the effect of heat shock protein(HSP)response on heat shock protein 72(HSP72)production in retinal ganglion cells(RGCs)of glaucoma model rats and its mechanism.Methods 64 Wistar rats were randomly divided into normal control group(normal rats),model group(glaucoma model),experimental group 1(glaucoma+intraperitoneal injection of zinc sulfate),experimental group 2(glaucoma+heat shock response intervention),16 rats in each group.In addition to the normal control group,the right eyes of the other three groups were treated with laser photocoagulation to compare the changes of intraocular pressure in the left and right eyes before and after laser treatment;the average density of RGCs and the level of HSP72 antibody in RGCs at different time points after the experiment were compared.Results There was no significant difference in intraocular pressure between the groups before and after laser treatment(P>0.05).The intraocular pressure of the right eye in model group,experimental group 1 and experimental group 2 were significantly higher than that before laser treatment(P<0.05),but there was no significant difference between the groups(P>0.05).In the normal control group,HSP72 antibody was not expressed in RGCs at different time points after the experiment;in the model group,HSP72 antibody was not expressed at 2 and 4 weeks after laser photocoagulation;in the experimental group 1 and experimental group 2,HSP72 antibody level gradually increased at 3 days to 2 weeks after laser treatment,peaked at 2 weeks,and then decreased to near normal level;in the experimental group 2,HSP72 antibody level at different time points was significantly higher than that in the model group and it was significantly lower than that of experimental group 1(P<0.05).Compared with the normal control group,the average density of RGCs in the model group,the experimental group 1 and the experimental group 2 decreased significantly(P<0.05).After laser treatment for 3 days,1 week,2 weeks and 4 weeks,the average density of RGCs in the experimental group 2 at different time points was significantly higher than that in the model group and the experimental group 1(P<0.05).Conclusion In the model of glaucoma rats,HSP72 can stimulate the production of HSP72 in RGCs through the intervention of HSP response,and has the function of protecting RGCs and optic nerve.