替米沙坦延缓大鼠视网膜衰老的作用及机制

摘要

目的 研究替米沙坦延缓大鼠生理性视网膜衰老的作用及潜在机制.方法 健康无眼疾SD大鼠40只,3个月龄大小,随机分为替米沙坦组和对照组,每组20只,饲养至9个月龄时开始给予干预,替米沙坦组用8 mg/(kg·d)替米沙坦灌胃,对照组大鼠用等容量生理盐水灌胃,至17个月龄.HE染色检测两组大鼠视网膜厚度及病理学改变;免疫组织化学染色检测视网膜氧化应激相关蛋白Cu-Zn-SOD、NOX2和凋亡相关蛋白Bcl-2、Bax的表达;采用Western blot法检测视网膜中p38 MAPK、NF-κB及其磷酸化水平(p-p38 MAPK、p-NF-κB)的表达.结果 视网膜HE染色显示:与对照组相比,替米沙坦组视网膜各层结构排列整齐,细胞形态基本一致,细胞丢失减少,视网膜厚度增加,差异有统计学意义(P<0.05).免疫组化结果显示:与对照组相比,替米沙坦组超氧化物歧化酶Cu-Zn-SOD的表达增强,过氧化物酶NOX2的表达减弱;凋亡相关蛋白Bcl-2的表达无明显变化(P>0.05),Bax的表达增强,Bcl-2/Bax的比值较对照组降低(P<0.05).Western blot结果显示:与对照组相比,替米沙坦组p-p38 MAPK、p-NF-κB的水平均降低,差异均有统计学意义(P<0.05).结论 替米沙坦可能通过降低p38 MAPK及NF-κB磷酸化水平,减轻视网膜氧化应激反应,增加细胞凋亡,进而延缓大鼠生理性视网膜衰老.%Objective To investigate the anti-aging effect of telmisartan on physiological aging of retinas in rats and its potential mechanisms. Methods A total of 40 three-month-old healthy SD rats which have no eye diseases, were randomly assigned to two groups:telmisartan group and control group, with 20 rats in each group. All rats were reared under the same conditions until they were nine-month old when interventions started to be given. Telmisartan group was given intragastric administration of 8 mg/kg telmisartan every day until 17-month old. Control group was given intragastric administration of same amount of saline gavage. Retinal thickness and pathological changes was measured by HE staining. The retinal oxidative stress related protein of Cu-Zn-SOD, NOX2 and apoptosis related pro-tein Bcl-2, Bax expression were determined by immunohistochemical assay. The expression of p38 MAPK, NF-κB, p-p38 MAPK, and p-NF-κB were detected by Western blot. Results The results of HE staining showed that the reti-nal structure was more clear, the morphology of cells were homogeneous, and the loss of cells was less in telmisartan group compared with control group. The total thickness of retina was also increased in telmisartan group (P<0.05). Im-munohistochemical analysis showed that the expression of Cu-Zn-SOD were increased, while the expression of NOX2 was decreased in telmisartan group compared with control group. There were no significant difference in the expression of Bcl-2 between the two groups (P>0.05). The expression of Bax was increased, and the ratio of Bcl-2/Bax was significantly lower than that of the control group (P<0.05). Western blot analysis showed that the phosphory-lation levels of p38 MAPK and NF-κB in telmisartan group were also increased compared with control group (P<0.05). Conclusion Telmisartan plays a protective role in retinal aging by decreasing oxidative stress reaction and pro-moting cell apoptosis through p38 MAPK and NF-κB signaling pathway.