Résumé
Diabetic nephropathy is a microvascular complication in the advanced stage of diabetes. About 20%-40% of patients with diabetes will progress to diabetic nephropathy. And worldwide, diabetic nephropathy has become the leading cause of end-stage renal disease. Animal model is a useful tool to study the pathogenesis and treatment of diabetic nephropathy. Currently, the commonly used diabetic nephropathy models all simulate partial characteristics of human diabetic nephropathy in different degrees of pathophysiology. However, the research on diabetic nephropathy has not achieved considerable progress. The main obstacle is that there is no effective animal model that can fully simulate all the characteristics of human diabetic nephropathy. In this paper, the animal models of diabetic nephropathy were reviewed from the aspects of modeling mechanism, pathophysiology, their advantages and disadvantages.
Résumé
Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD). Visual dysfunction is commonly found and is positively correlated with the severity of cognitive defects in AD patients. Our previous study demonstrated that Hhcy induces memory deficits with AD-like tau and amyloid-β (Aβ) pathologies in the hippocampus, and supplementation with folate and vitamin B12 (FB) prevents the Hhcy-induced AD-like pathologies in the hippocampus. Here, we investigated whether Hhcy also induces AD-like pathologies in the retina and the effects of FB. An Hhcy rat model was produced by vena caudalis injection of homocysteine for 14 days, and the effects of FB were assessed by simultaneous supplementation with FB in drinking water. We found that Hhcy induced vessel damage with Aβ and tau pathologies in the retina, while simultaneous supplementation with FB remarkably attenuated the Hhcy-induced tau hyperphosphorylation at multiple AD-related sites and Aβ accumulation in the retina. The mechanisms involved downregulation of amyloid precursor protein (APP), presenilin-1, beta-site APP-cleaving enzyme 1, and protein phosphatase-2A. Our data suggest that the retina may serve as a window for evaluating the effects of FB on hyperhomocysteinemia-induced Alzheimer-like pathologies.