氨基胍高选择性抑制iNOS在糖尿病大鼠视网膜中的研究

摘要

Objective To investigate the treatment and mechanism of aminoguanidine in retina of diabetic of rats .Methods To-tal 60 rats were divided into control group(n=20) ,diabetic group(n=20) and aminoguanidine treatment group(n=20)which would be treated by aminoguanidine for 14 days .Then the eye tissue of rats were took after 14 days administration for pathological obser-vation(HE staining) ,and the induced nitric oxide synthase(iNOS) ,endothelial nitric oxide synthase(eNOS) ,nerve type of nitric ox-ide synthase(nNOS) level and the expression of differences content and expression were investigated by ELISA ,Western blot and PT-PCR .Results HE staining showed that retinal tissue defects decreased and neuronal cells of rats in aminoguanidine treatment group were increased and significant (P<0 .05) compared rats in diabetic group .The iNOS content and expression of rats in amin-oguanidine treatment group were lower than diabetic group by ELISA ,Western blot and PT-PCR ,it was significantly difference (P<0 .05) and without significant difference between the normal group and diabetic group (P> 0 .05) .Compared with diabetes group ,iNOS ,eNOS ,nNOS protein expression in the rat retina in aminoguanidine treatment group were reduced (P< 0 .05) ,and without significant difference between the normal group and aminoguanidine treatment group (P>0 .05) .The iNOS mRNA expres-sion was lower than that of eNOS mRNA and nNOS mRNA in aminoguanidine treatment group .Conclusion Aminoguanidine can improve retinal tissue of diabetic rats with lesions ,the pathways may be selectively inhibit inducible nitric oxide synthase activity of iNOS .%目的：探讨氨基胍对糖尿病大鼠视网膜的治疗作用及机制。方法60只大鼠分为对照组（n＝20）、糖尿病组（n＝20）、氨基胍治疗组（n＝20），给药14 d后取大鼠眼组织进行病理学观察（HE染色），采用ELISA、Western blot、PT-PCR检测各组大鼠诱导型一氧化氮合酶（iNOS ）、内皮细胞性一氧化氮合酶（eNOS ）、神经型一氧化氮合酶（nNOS ）水平及表达的差异。结果H E染色结果显示，氨基胍治疗组与糖尿病组比较，大鼠视网膜组织缺损明显降低，神经元细胞增多。氨基胍治疗组、对照组iN-OS水平显著低于糖尿病组，对照组nNOS水平明显低于其他两组；3组eNOS水平差异无统计学意义（P＞0．05）。氨基胍治疗组与糖尿病组比较，iNOS蛋白表达降低（P＜0．05），与对照组比较差异无统计学意义（P＞0．05）。氨基胍治疗组大鼠iNOS mRNA表达低于eNOS mRNA和nNOS mRNA。结论氨基胍可以改善糖尿病大鼠视网膜组织病变，作用途径可能是选择性地抑制iNOS的活性。