Mitochondria-Targeted Antioxidant Peptide SS31 Protects the Retinas of Diabetic Rats
Mitochondria-Targeted Antioxidant Peptide SS31 Protects the Retinas of Diabetic Rats
复制标题
线粒体靶向抗氧化肽 SS31 保护糖尿病大鼠的视网膜
DOI：
10.2174/15665240113139990049
复制
发表时间：
2013-07-01
影响因子：
2.5
通讯作者：
Luo, Y.
中科院分区：
文献类型：
--
作者：
Huang, J.;Li, X.;Luo, Y.
氧化应激是糖尿病视网膜病变发病机制中的主要因素之一。本研究的目的是研究抗氧化肽SS 31对链脲佐菌素（STZ）诱导的糖尿病大鼠视网膜的影响。造模后2周，每天于糖尿病大鼠背部皮下注射SS 31（3 mg/kg）或等量生理盐水（N.S）。4个月后，用伊文思蓝灌注法检测血视网膜内屏障（iBRB）的完整性。免疫荧光染色检测大鼠视网膜中claudin-5、occludin、acrolein、8-OHdG和硝基酪氨酸的表达和分布。透射电镜观察视网膜超微结构。Western blot检测VEGF 2、Trx-2、Bcl-2、Bax、caspase-3、p53、NF-κ B B蛋白表达水平。皮下注射SS 31后4个月，糖尿病大鼠视网膜神经节细胞结构更好，毛细血管基底膜更薄，iBR B渗漏更少，视网膜血管中claudin-5和occludin染色更均匀，丙烯醛、8-OHdG、硝基酪氨酸、Bax、caspase-3、p53和NF-κ B水平更低，视网膜中Trx-2和Bcl-2的水平高于NS处理组。结论：SS 31可通过减少糖尿病大鼠视网膜的氧化损伤，增加Trx-2和Bcl-2的表达，降低p53、NF-κ B、Bax、caspase-3和VEGFR 2的表达，保护视网膜结构，抑制iBR B的降解。SS 31可能是糖尿病视网膜病变和其他氧化应激相关疾病的潜在新治疗方法。
Oxidative stress is one of the main contributors in the pathogenesis of diabetic retinopathy. The aim of this study is to investigate the effects of SS31 which is a mitochondria-targeted antioxidant peptide on the retinas of streptozotocin (STZ)-induced diabetic rats. Two weeks after induction of diabetes, SS31 (3 mg/kg) or the same volume of normal saline (N.S) was injected subcutaneously into the back of diabetic rats every day. Four months later, the integrity of inner blood retinal barrier (iBRB) was measured by Evans blue perfusion. The expression and distribution of claudin-5, occludin, acrolein, 8-OHdG and nitrotyrosine in the rat retinas were detected by immunofluorescent staining. Retinal ultrastructures were observed by transmission electron microscopy. The protein level of VEGFR2, Trx-2, Bcl-2, Bax, caspase-3, p53, and NF-kappa B in the rat retinas were assayed by western blot. Four months after subcutaneous injection, the diabetic rats treated with SS31 had better structures of retinal ganglion cells, thinner capillary basement membrane, less iBRB leakage, more uniform staining of claudin-5 and occludin in the retinal vessels, lower levels of acrolein, 8-OHdG, nitrotyrosine, Bax, caspase-3, p53, and NF-kappa B, and higher levels of Trx-2 and Bcl-2 in the retinas than those treated with N.S. In conclusion, SS31 could protect the retinal structures and inhibit the breakdown of iBRB by reducing oxidative damage, increasing Trx-2 and Bcl-2 expression, and decreasing p53, NF-kappa B, Bax, caspase-3, and VEGFR2 expression in the retinas of diabetic rats. SS31 could be a potential new treatment for diabetic retinopathy and other oxidative stress-related diseases.