摘要
目的 探讨福辛普利(Fos)对链脲佐菌素(STZ)诱导糖尿病视网膜病变(DR)小鼠的保护作用,及其对DR小鼠血管紧张素转化酶2(ACE2)和血管内皮生长因子(VEGF)表达的影响。方法 48只健康雄性昆明小鼠随机抽取36只,高脂饲料喂养6周后用SZT诱导制作糖尿病小鼠模型。模型制作成功后随机分为3组:模型组、Fos低浓度(5 mg/kg)组和Fos高浓度(10 mg/kg)组。12只小鼠为对照组。连续给药8周后,观察各组小鼠体质量和血糖变化,通过视网膜组织HE染色观察视网膜结构变化,采用ELISA法测定小鼠血清VEGF水平,运用免疫组织化学法观测小鼠视网膜组织ACE2的表达,Real-time PCR检测小鼠视网膜ACE2 mRNA表达,Western blotting检测小鼠视网膜ACE2和VEGF蛋白水平。结果 Fos(5 mg/kg和10 mg/kg)能够显著减轻糖尿病小鼠视网膜内界膜层新生血管增生,下调糖尿病小鼠升高的血清中VEGF表达,促进糖尿病小鼠视网膜组织ACE2表达,Fos高浓度组作用效果较低浓度组好(P<0.05)。结论 福辛普利对糖尿病小鼠视网膜病变有保护作用,这种保护作用可能与上调ACE2的表达,降低VEGF表达有关。
Objective To explore the protective effect of fosinopril(Fos) on streptozotocin(STZ) induced diabetic retinopathy(DR) mice and on the expression of angiotensin converting enzyme 2(ACE2) and vascular endothelial growth factor(VEGF) in DR mice. Methods Totally forty-eight healthy male Kunming mice, thirty-six were randomly selected, and a diabetic mouse model induced by STZ was constructed after 6 weeks of high-fat diet. After the successful establishment of the model, the thirty-six mice were randomly divided into three groups: model group, Fos low concentration(5 mg/kg) group, and Fos high concentration(10 mg/kg) group. The remaining twelve mice were served as the control group. After 8 weeks administration, the body weight and blood glucose level of mice in each group were determined. The change in the retinal structure was verified by HE staining. The serum level of VEGF was measured by ELISA. The expression of ACE2 in the retina tissue was verified by immunohistochemistry. The expression of ACE2 mRNA in diabetic retinopathy was analyzed by Real-time PCR. The levels of ACE2 and VEGF protein in diabetic retinopathy were detected by Western blotting. Results Fos(5 mg/kg, 10 mg/kg) reduced significantly the proliferation of neovascularization in the inner boundary layer, down-regulated the expression of VEGF in the serum of diabetic mice and promoted the expression of ACE2 in the retina tissue of diabetic mice. In addition, the effect of the high concentration group of Fos had a stronger effect than the lower concentration group(P<0.05). Conclusion Fos has a protective effect on the retinopathy of diabetic mice. This protective effect may be mediated through the increased expression of ACE2 and the reduction of VEGF expression.
作者
张琴
杨俊霞
蒋青松
ZHANG Qin;YANG Jun-xia;JIANG Qing-song(Chongqing Emergency Medical Center,Department of Pharmacy,Chongqing Fourth People’s Hospital,Chongqing 400014,China;Department of Pharmacology,College of Pharmacy,Chongqing Medical University,Chongqing 400016,China)
出处
《解剖学报》
CAS
CSCD
北大核心
2023年第6期628-634,共7页
Acta Anatomica Sinica
基金
国家自然科学基金(30600812,81100905)
重庆市临床药学重点专科建设项目(渝卫办发[2020]68号)。