Preet Anju, Siddiqui M R, Taha A, Badhai J, Hussain M E, Yadava P K, Baquer N Z
Hormone and Drug Research Laboratory, Applied Molecular Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Mol Cell Biochem. 2006 Sep;289(1-2):137-47. doi: 10.1007/s11010-006-9156-0. Epub 2006 May 23.
Trigonella foenum graecum seed powder (TSP) and Sodium Orthovanadate (SOV) have been shown to demonstrate antidiabetic effects by stabilizing glucose homeostasis and carbohydrate metabolism in experimental type-1 diabetes. However their efficacy in controlling histopathological and biochemical abnormalities in ocular tissues associated with diabetic retinopathy is not known. The purpose of this study was to investigate the comparative efficacy of individual as well as combination therapy of TSP and SOV in 8 weeks diabetic rat lens and retina. Retinas and lenses were taken from control, alloxan-induced diabetic rats and diabetic rats treated separately with insulin, 5%TSP, SOV (0.6 mg/ml) and a combined dose of SOV (0.2 mg/ml) and 5%TSP for 60 days. Control and each experimental group had six rats. Alterations in the activities of enzymes HK (hexokinase), AR (aldose reductase), SDH (sorbitol dehydrogenase), G-6-PD (glucose-6-phosphate dehydrogenase), GPx (glutathione peroxidase), GR (glutathione reductase) and levels of metabolites like sorbitol, fructose, glucose, MDA (malondialdehyde) and GSH (reduced glutathione) were measured in the cytosolic fraction of lenses besides measuring blood glucose levels and glycosylated haemoglobin. Histopathological abnormalities were studied in the lens using photomicrography and retina using transmission electron microscopy. Blood glucose, glycosylated haemoglobin levels and polyol pathway enzymes AR and SDH increased significantly causing accumulation of sorbitol and fructose in the diabetic lens and treatment with SOV and TSP significantly (p < 0.05) decreased these to control levels. Similarly, SOV and TSP treatments modulated the activities of HK, G-6-PD, GPx and GR in the rat lens to control values. Ultrastructure of the diabetic retina revealed disintegration of the inner nuclear layer cells with reduction in rough endoplasmic reticulum and swelling of mitochondria in the bipolar cells; and these histopathological events were effectively restored to control state by SOV and TSP treatments. In this study SOV and TSP effectively controlled ocular histopathological and biochemical abnormalities associated with experimental type-1 diabetes, and a combination regimen of low dose of SOV with TSP demonstrated the most significant effect. In conclusion, the potential of SOV and TSP alone or in low dose combination may be considered as promising approaches for the prevention of diabetic retinopathy and other ocular disorders.
胡芦巴籽粉（TSP）和原钒酸钠（SOV）已被证明可通过稳定实验性1型糖尿病中的葡萄糖稳态和碳水化合物代谢来发挥抗糖尿病作用。然而，它们在控制与糖尿病视网膜病变相关的眼组织中的组织病理学和生化异常方面的功效尚不清楚。本研究的目的是调查TSP和SOV单独以及联合治疗对8周龄糖尿病大鼠晶状体和视网膜的比较疗效。从对照组、四氧嘧啶诱导的糖尿病大鼠以及分别用胰岛素、5%TSP、SOV（0.6 mg/ml）以及SOV（0.2 mg/ml）与5%TSP的联合剂量治疗60天的糖尿病大鼠中获取视网膜和晶状体。对照组和每个实验组有6只大鼠。除了测量血糖水平和糖化血红蛋白外，还测量了晶状体胞质部分中己糖激酶（HK）、醛糖还原酶（AR）、山梨醇脱氢酶（SDH）、葡萄糖-6-磷酸脱氢酶（G-6-PD）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）等酶的活性以及山梨醇、果糖、葡萄糖、丙二醛（MDA）和还原型谷胱甘肽（GSH）等代谢物的水平。使用显微镜摄影研究晶状体的组织病理学异常，使用透射电子显微镜研究视网膜的组织病理学异常。糖尿病晶状体中的血糖、糖化血红蛋白水平以及多元醇途径酶AR和SDH显著升高，导致山梨醇和果糖积累，而SOV和TSP治疗可显著（p < 0.05）将这些指标降至对照水平。同样，SOV和TSP治疗将大鼠晶状体中HK、G-6-PD、GPx和GR的活性调节至对照值。糖尿病视网膜的超微结构显示内核层细胞解体，双极细胞中的粗面内质网减少，线粒体肿胀；而SOV和TSP治疗有效地将这些组织病理学事件恢复到对照状态。在本研究中，SOV和TSP有效地控制了与实验性1型糖尿病相关的眼部组织病理学和生化异常，低剂量SOV与TSP的联合方案显示出最显著的效果。总之，单独使用SOV和TSP或低剂量联合使用的潜力可被视为预防糖尿病视网膜病变和其他眼部疾病的有前景的方法。
