The protective effects of cyclosporine A on aortic immunological injuries in STZ-induced diabetic rats
10.3760/cma.j.issn.0253-3758.2010.05.015
- VernacularTitle:环孢素A对链脲菌素诱导的糖尿病大鼠主动脉免疫损伤的保护作用
- Author:
Jin CUI
1
;
Ming-Cai QIU
;
De-Qiang LI
;
Xin ZHANG
;
Jin-Shi ZHANG
;
Peng ZHANG
Author Information
1. 天津医科大学总医院
- Keywords:
Diabetic angiopathies;
Immunoglobulins;
Immunosuppressive agents;
Cyclosporine
- From:
Chinese Journal of Cardiology
2010;38(5):440-444
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the autoimmune injuries of diabetic macrovascular disease (aorta) and the protective effects of immunosuppressive agent (cyclosporine A, CsA) on aortic injuries in streptozotocin (STZ) -induced diabetic rats. Methods STZ-induced diabetic rats were assigned randomly to 6 groups which received low (BML or AML, 1 mg·kg-1·d-1) , middle ( BMM or AMM, 4 mg · kg-1 ·d-1) or high (BMH or AMH, 8 mg ·kg-1 · d-1) dose of CsA from 1 week before or after STZ for 8 weeks.Diabetic rats without any treatment, insulin-treated diabetic rats and normal rats were also monitored simultaneously and served as control groups. The pathologic abnormalities of the aorta were verified by HE, Masson staining and electromicroscopy. The depositions of immunoglobulins (IgG, IgM and IgA) were determined by immunohistochemistry and immunofluorescence methods. Results At the end of study, lymphocytes infiltration and collagen content (26 582 ±6901) were significantly higher in diabetic aorta than those in non-diabetic aorta ( Collagen: 7482 ± 3491, P < 0. 01). The deposited IgG and IgA were also significantly increased in diabetic aorta compared with non-diabetic aorta (IgG: H 789 ±2491 vs. 2S18 ± 1066, P<0. 01; IgA: 17 430 ±3159 vs. 1135 ±758, P<0.01). These changes were not affected by insulin while CsA intervention significantly reduced aortic collagen content (BMH: 13 518 ±5440, P <0. 01 vs. STZ) and immunoglobulin deposition (BMH: IgG:7584 ±4462; IgA: 6176 ±1900, all P<0.01 vs. STZ). These immunoglobulin deposition changes were confirmed by results of immunofluorescence. Aortic collagen accumulation was positively correlated to aortio immunoglobulin deposition (IgG, r = 0. 556, P < 0. 01; IgA, r =0. 661, P<0. 01). Conclusions Our data suggest that the autoimmune injuries might be a promoting factor in the pathogenesis of the diabetic macrovascular disease which could lead to the development of macrovascular disease. Immunosuppressive agent, such as CsA, could inhibit the abnormal deposition of immunoglobulins and therefore, delay the development of diabetic macrovascular disease in this model.
