Diabetes is associated with increased blood brain barrier (BBB) permeability resulting in neurological deficits. The present study investigated the role of S-nitrosoglutathione (GSNO) on tight junction proteins and cell adhesion molecules in streptozotocin-induced diabetic mice. Diabetes was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) for 5 days in mice. GSNO was administered daily (100 μg/kg body weight, orally) for 8 weeks after the induction of diabetes. A significant decline was observed in the cognitive ability of diabetic animals assessed using radial arm maze test. A significant increase was observed in nitrotyrosine levels in cortex and hippocampus of diabetic mice. Relative mRNA and protein expression of tight junction proteins viz; zona occludens-1 (ZO-1) and occludin were significantly lower in the microvessels isolated from cortex and hippocampus of diabetic animals, whereas expression of claudin-5 was unaltered. Immunofluorescence of tight junction proteins confirmed loss of ZO-1 and occludin in the diabetic brain. Furthermore, significant increase in interstitial cell adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 mRNA and protein levels was observed in diabetic animals. Ultrastructure of microvessels from diabetic brain was also altered thereby confirming BBB disruption. GSNO administration to diabetic animals, on the other hand, was able to ameliorate loss of ZO-1 and occludin as well as normalize ICAM-1 and VCAM-1 expression, restore BBB integrity, and improve cognitive deficits. The findings clearly suggest that GSNO is a therapeutic molecule with potential to protect BBB and prevent diabetes induced neurological deficits.

糖尿病与增加的血脑屏障（BBB）通透性相关，从而导致神经功能缺损。本研究调查了链脲佐菌素诱导的糖尿病小鼠中S-亚硝基谷胱甘肽（GSNO）对紧密连接蛋白和细胞粘附分子的作用。在小鼠中腹膜内注射链脲佐菌素（40 mg / kg体重）诱导糖尿病5天。诱导糖尿病后，每天（以100μg/ kg体重口服）给予GSNO，持续8周。使用radial臂迷宫测试评估的糖尿病动物的认知能力显着下降。观察到糖尿病小鼠的皮质和海马中的硝基酪氨酸水平显着增加。紧密连接蛋白的相对mRNA和蛋白表达 从糖尿病动物的皮质和海马分离出的微血管中，透明带1（ZO-1）和闭合蛋白显着降低，而claudin-5的表达未改变。紧密连接蛋白的免疫荧光证实了糖尿病脑中ZO-1和occludin的丢失。此外，在糖尿病动物中观察到间质细胞粘附分子（ICAM）-1和血管细胞粘附分子（VCAM）-1 mRNA和蛋白质水平的显着增加。来自糖尿病脑的微血管的超微结构也被改变，从而证实了血脑屏障的破坏。另一方面，GSNO对糖尿病动物的给药能够改善ZO-1和闭合蛋白的丢失，并使ICAM-1和VCAM-1的表达正常化，恢复BBB的完整性，并改善认知功能障碍。