动物造模,糖尿病肥胖 z-bio 2022-10-10 529

　　Objective: To observe the pathological characteristics of cerebrovascular disease in Zucker diabetic obese (ZDF) rats, and to preliminarily explore its pathogenesis, so as to provide experimental basis and theoretical basis for the application of ZDF rats.

　　Methods: 8 male ZDF rats aged 8-9 weeks were selected and fed Purina#5008 diet for 12 weeks, and another 8 male Zucker lean (ZL) rats of the same age were fed normal diet as normal control group. After the feeding period, the body weight, fasting blood glucose and glycosylated hemoglobin (HbA1c) of the rats in each group were detected, the cognitive function of the rats was evaluated by the Y-maze, the general shape of the intracranial blood vessels was observed by magnetic resonance imaging, and the animals were sacrificed and the brain tissue was collected. Routine pathology and ultrastructural pathology were used to observe macrovascular and microvascular lesions in brain tissue, and immunofluorescence techniques were used to observe albumin, IgG leakage, and the expression of tight junction proteins Occludin and ZO-1.

　　Results: Compared with the ZL rats in the normal control group, the body weight, fasting blood glucose and HbA1c of the ZDF rats in the model control group were significantly increased at 20 weeks of age (P<0.01); the time spent in the new arm in the Y-maze test Significantly decreased (P<0.05); large vessels in the brain were deformed and segmental stenosis; cerebral microvessels were occluded, peripheral nerve fibers edema; albumin and IgG exuded around cerebral vessels, and the expression of ZO-1 and Occludin proteins decreased ( P<0.01).

　　CONCLUSION: ZDF rats develop cognitive dysfunction at 20 weeks of age, stenosis and occlusion of large intracranial vessels and microvessels, and cause peripheral nerve tissue lesions. The pathogenesis may be that the loss of tight junction protein leads to the destruction of blood-brain barrier , increased permeability, resulting in vascular morphological and functional lesions.