CAJ | 학술논문

目的探讨糖尿病大血管病变发病过程中的免疫机制,观察免疫抑制剂环孢素A(CsA)对糖尿病大鼠主动脉免疫损伤的保护作用.方法以链脲菌素诱导的糖尿病大鼠为模型,随机分为正常对照组、单纯糖尿病组、胰岛素治疗组以及CsA治疗组[包括造模前低剂量组(BML)、造模前中剂最组(BMM)、造模前高剂量组(BMH)、造模后低剂量组(AML)、造模后中剂量组(AMM)和造模后高剂量组(AMH)],其中各CsA治疗组分别于造模前或成模后按1、4、8 mg·kg-1·d-1予CsA皮下注射.8周后处死动物,通过病理组织学和超微病理学观察糖尿病大鼠主动脉病变程度,以免疫组化和荧光检测主动脉壁免疫球蛋白沉积状况,以积分吸光度(IA)对其结果进行分析.结果 8周时,单纯糖尿病组主动脉中膜层可见淋巴细胞浸润,胶原纤维A值由7482 ±3491增加至26 582±6901(P<0.01),并有大量IgG和IgA沉积,IA值分别由2518±1066和1135±758增加至11 789±2491和17 430±3159(P均<0.01).胰岛素治疗组胶原纤维和免疫球蛋白的异常沉积与糖尿病组比较差异无统计学意义.CsA可明显降低糖尿病大鼠动脉胶原纤维(BMH:13 518 ±5440,P<0.01)和免疫球蛋白沉积(BMH IgG:7584 ±4462,IgA:6176 ±1900,P均<0.01).免疫荧光检测示各组免疫球蛋白沉积的差异均具有统计学意义(IgG:χ2=41.227,P<0.01;IgA:χ2=41.129,P<0.01;IgM:χ2=29.891,P<0.01).且主动脉IgG和IgA的沉积均与动脉壁胶原纤维含量呈显著性正相关(IgG:r=0.556,P<0.01;IgA:r=0.661,P<0.01).结论免疫机制可能参与糖尿病大血管病变的发生.CsA能有效地减少免疫球蛋白沉积,可能具有延缓糖尿病大血管病变的作用.
목적 탐토당뇨병대혈관병변발병과정중적면역궤제,관찰면역억제제배포소A(CsA)대당뇨병대서주동맥면역손상적보호작용.방법 이련뇨균소유도적당뇨병대서위모형,수궤분위정상대조조、단순당뇨병조、이도소치료조이급CsA치료조[포괄조모전저제량조(BML)、조모전중제최조(BMM)、조모전고제량조(BMH)、조모후저제량조(AML)、조모후중제량조(AMM)화조모후고제량조(AMH)],기중각CsA치료조분별우조모전혹성모후안1、4、8 mg·kg-1·d-1여CsA피하주사.8주후처사동물,통과병리조직학화초미병이학관찰당뇨병대서주동맥병변정도,이면역조화화형광검측주동맥벽면역구단백침적상황,이적분흡광도(IA)대기결과 진행분석.결과 8주시,단순당뇨병조주동맥중막층가견림파세포침윤,효원섬유A치유7482 ±3491증가지26 582±6901(P<0.01),병유대량IgG화IgA침적,IA치분별유2518±1066화1135±758증가지11 789±2491화17 430±3159(P균<0.01).이도소치료조효원섬유화면역구단백적이상침적여당뇨병조비교차이무통계학의의.CsA가명현강저당뇨병대서동맥효원섬유(BMH:13 518 ±5440,P<0.01)화면역구단백침적(BMH IgG:7584 ±4462,IgA:6176 ±1900,P균<0.01).면역형광검측시각조면역구단백침적적차이균구유통계학의의(IgG:χ2=41.227,P<0.01;IgA:χ2=41.129,P<0.01;IgM:χ2=29.891,P<0.01).차주동맥IgG화IgA적침적균여동맥벽효원섬유함량정현저성정상관(IgG:r=0.556,P<0.01;IgA:r=0.661,P<0.01).결론 면역궤제가능삼여당뇨병대혈관병변적발생.CsA능유효지감소면역구단백침적,가능구유연완당뇨병대혈관병변적작용.
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.