早期糖尿病大鼠视网膜一氧化氮合酶亚型表达与血流动力学变化的关系

Relationship between expression of nitric oxide synthase isoforms and hemodynamic changes in retina in early diabetic rats

目的探讨糖尿病早期3种一氧化氮合酶(NOS)亚型在视网膜中的蛋白表达及其与视网膜血流动力学变化的关系.方法将20只Wistar大鼠随机分为对照组与链脲佐菌素腹腔注射诱导的糖尿病组,每组各10只.采用彩色多普勒检测2组大鼠视网膜中央动脉(CRA)的收缩期峰值血流速度(PSV)、舒张期最低流速(EDV)、阻力指数(RI)及搏动指数(PI),并采用免疫组织化学分析法观察视网膜内皮型NOS(eNOS)、诱导型NOS(iNOS)和神经元型NOS(nNOS)的蛋白表达.结果饲养8周后检测糖尿病组大鼠视网膜尚未出现明确病变,但大鼠视网膜CRA的PSV、EDV较对照组降低(P＜0.05),而RI、PI出现升高趋势(P＞0.05).2组NOS的3种亚型在视网膜的蛋白表达部位一致,但糖尿病组iNOS的蛋白表达增强,eNOS与nNOS蛋白表达未见明显变化.结论糖尿病早期视网膜血流动力学的异常可能与iNOS的表达增强有关.

Objective To evaluate the relationship between expressions of isoforms of nitric oxide synthase （NOS） and hemodynamic changes in retina in rats with early stages of diabetes. Methods Twenty Wistar rats were randomly divided into control group （ n = 10 ） and streptozotocin-induced diabetic group （ n = 10 ）. The blood flow indexes of central retinal artery （ CRA）, including peak systolic velocity （ PSV）, end diastolic velocity （EDV）, resistance index （RI） and pulsitive index （PI） were measured by color Doppler imaging. Protein expressions of endothelial NOS （ eNOS）, inducible NOS （iNOS） and neuronal NOS （nNOS） in rat retina were examined by immunohistochemical analysis. Results Compared with the control group, the velocity of blood flow （ PSV and EDV） in CRA decreased significantly （ P 〈 0.05 ） , while diabetic retinopathy was still not found in g-week diabetic rats. The RI and PI increased without statistical significance （P 〉 0.05 ）. At the same stage, the protein expression of iNOS was the only one which increased in diabetic retina although the 3 isoforms of NOS in diabetic group expressed at the same sites as in the control group with no significant change of eNOS and nNOS protein expression. Conclusion It is suggested that the hemodynamic changes of retina are correlated with the increased expression activity of iNOS in retina in early diabetic rats.