[The protective effects of cyclosporine A on aortic immunological injuries in STZ-induced diabetic rats].
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 mgxkg(-1)xd(-1)), middle (BMM or AMM, 4 mgxkg(-1)xd(-1)) or high (BMH or AMH, 8 mgxkg(-1)xd(-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 electronmicroscopy. 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: 11 789 +/- 2491 vs. 2518 +/- 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 aortic 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.
Cui
Jin
J
Department of Endocrinology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
Qiu
Ming-cai
MC
Li
De-qiang
DQ
Zhang
Xin
X
Zhang
Jin-shi
JS
Zhang
Peng
P
D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology*; D001018:Aortic Diseases / Q000209:etiology; D016572:Cyclosporine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007166:Immunosuppressive Agents; D016572:Cyclosporine