环孢素A对晚期糖尿病大鼠多器官的保护作用
배포소A대만기당뇨병대서다기관적보호작용
Protective effects of cyclosporine A on multiple organs in diabetic rats at advanced stage
  • 万方数据
    中国中西医结合急救杂志 중국중서의결합급구잡지
    Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
    2015年 5期 472-477 ,共6页

    姜丽娟%戴红双%尹晓梅%孔伟%李菁爽%王华%张云霞%盛艳丽%黄晓玲%韩会民

    강려연%대홍쌍%윤효매%공위%리정상%왕화%장운하%성염려%황효령%한회민

    糖尿病%环孢素A%免疫球蛋白%核转录因子-κB%转化生长因子-β1 糖尿病%環孢素A%免疫毬蛋白%覈轉錄因子-κB%轉化生長因子-β1
    당뇨병%배포소A%면역구단백%핵전록인자-κB%전화생장인자-β1
    Diabetes%Cyclosporin A%Immunoglobulin%Nuclear factor-κB%Transforming growth factor-β1
    目的 观察晚期糖尿病(DM)大鼠肝、肾、肺、心肌、主动脉、视网膜的病理学改变,以及环孢素A(CsA)对上述器官是否具有保护作用.方法 30只Wistar雄性大鼠按随机数字表法分为CsA组、DM模型组、正常对照组(CON组)3组,每组10只.采用一次性腹腔注射链脲佐菌素(STZ)55 mg/kg的方法制备晚期DM大鼠模型,48 h后取尾静脉血测血糖,2次血糖均>16.7 mmol/L为制模成功.CsA组于饲养28周时给予CsA 3 mg·kg-1·d-1 6周;CON组不做任何处理.全部动物成模34周后处死取肝、肾、肺、主动脉、心肌、视网膜,采用苏木素-伊红(HE)染色、Masson染色观察病理学改变,用免疫组化染色检测上述器官免疫球蛋白(IgG、IgA)及核转录因子-κB(NF-κB)、转化生长因子-β1(TGF-β1)表达水平的变化.结果 DM模型组大鼠死亡 1只,CsA组死亡2只,分别以9只、8只纳入统计学分析.①HE染色:DM模型组肝小叶结构紊乱,肾小球体积明显肥大,肺泡隔增宽,主动脉管壁中可见淋巴细胞浸润,心肌细胞肥大,视网膜内核层、外核层细胞排列紊乱;CsA组上述变化较DM模型组减轻.②Masson染色:DM模型组肝小叶内可见散在的胶原纤维沉积,肾小球内胶原明显增多,肺间质胶原纤维明显增多,主动脉、心肌胶原纤维增多,视网膜未见明显阳性反应;CsA组上述变化减轻.③ 免疫组化分析显示:与CON组比较,DM模型组肝、肾、肺、主动脉、心肌、视网膜IgG、IgA、NF-κB、TGF-β1表达〔均用吸光度(A)值表示〕均明显增多;与DM模型组比较,CsA组各指标表达均降低 (肝:IgA:110 059±22 321比151 055±12 481,IgG:106 265±39 225比158 296±65 723,NF-κB:95 638±6 045比130 650±9 257,TGF-β1:102 856±10 631比263 380±75 264;肾:IgA:37 305±8 340比53 281±5 412, IgG:35 521±9 310比77 092±8 953,NF-κB:37 768±2 622比54 888±2 494,TGF-β1:48 425±1 170比62 687±8 593;肺:IgA:94 022±1 701比198 977±38 135,IgG:60 771±3 033比132 987±18 287,NF-κB:100 900±49 842比156 153±25 756,TGF-β1:132 330±42 627比177 707±21 156;主动脉:IgA:88 069± 2 321比108 053±41 481,IgG:109 260±35 328比178 792±56 763,NF-κB:75 638±7 053比90 650±9 357, TGF-β1:122 456±85 631比294 380±85 764,心肌:IgA:102 516±9 390比99 326±85 232,IgG:86 528± 12 650比194 226±68 473,NF-κB:98 258±8 235比190 966±57 856,TGF-β1:95 632±5 624比196 753± 92 020,视网膜:IgA:7 259±6 221比12 013±4 012,IgG:10 660±9 328比16 592±6 163,NF-κB:9 828±853比12 350±6 357,TGF-β1:10 233±6 011比16 880±4 574,P<0.05或P<0.01).结论 IgG、IgA、NF-κB、TGF-β1异常表达可能与DM肝脏、肾脏、肺脏、心肌、主动脉、视网膜损害有关,免疫和炎症因素可能参与其中, CsA可能通过下调IgG、IgA、NF-κB、TGF-β1表达,从而减轻DM多器官改变.
    목적 관찰만기당뇨병(DM)대서간、신、폐、심기、주동맥、시망막적병이학개변,이급배포소A(CsA)대상술기관시부구유보호작용.방법 30지Wistar웅성대서안수궤수자표법분위CsA조、DM모형조、정상대조조(CON조)3조,매조10지.채용일차성복강주사련뇨좌균소(STZ)55 mg/kg적방법제비만기DM대서모형,48 h후취미정맥혈측혈당,2차혈당균>16.7 mmol/L위제모성공.CsA조우사양28주시급여CsA 3 mg·kg-1·d-1 6주;CON조불주임하처리.전부동물성모34주후처사취간、신、폐、주동맥、심기、시망막,채용소목소-이홍(HE)염색、Masson염색관찰병이학개변,용면역조화염색검측상술기관면역구단백(IgG、IgA)급핵전록인자-κB(NF-κB)、전화생장인자-β1(TGF-β1)표체수평적변화.결과 DM모형조대서사망 1지,CsA조사망2지,분별이9지、8지납입통계학분석.①HE염색:DM모형조간소협결구문란,신소구체적명현비대,폐포격증관,주동맥관벽중가견림파세포침윤,심기세포비대,시망막내핵층、외핵층세포배렬문란;CsA조상술변화교DM모형조감경.②Masson염색:DM모형조간소협내가견산재적효원섬유침적,신소구내효원명현증다,폐간질효원섬유명현증다,주동맥、심기효원섬유증다,시망막미견명현양성반응;CsA조상술변화감경.③ 면역조화분석현시:여CON조비교,DM모형조간、신、폐、주동맥、심기、시망막IgG、IgA、NF-κB、TGF-β1표체〔균용흡광도(A)치표시〕균명현증다;여DM모형조비교,CsA조각지표표체균강저 (간:IgA:110 059±22 321비151 055±12 481,IgG:106 265±39 225비158 296±65 723,NF-κB:95 638±6 045비130 650±9 257,TGF-β1:102 856±10 631비263 380±75 264;신:IgA:37 305±8 340비53 281±5 412, IgG:35 521±9 310비77 092±8 953,NF-κB:37 768±2 622비54 888±2 494,TGF-β1:48 425±1 170비62 687±8 593;폐:IgA:94 022±1 701비198 977±38 135,IgG:60 771±3 033비132 987±18 287,NF-κB:100 900±49 842비156 153±25 756,TGF-β1:132 330±42 627비177 707±21 156;주동맥:IgA:88 069± 2 321비108 053±41 481,IgG:109 260±35 328비178 792±56 763,NF-κB:75 638±7 053비90 650±9 357, TGF-β1:122 456±85 631비294 380±85 764,심기:IgA:102 516±9 390비99 326±85 232,IgG:86 528± 12 650비194 226±68 473,NF-κB:98 258±8 235비190 966±57 856,TGF-β1:95 632±5 624비196 753± 92 020,시망막:IgA:7 259±6 221비12 013±4 012,IgG:10 660±9 328비16 592±6 163,NF-κB:9 828±853비12 350±6 357,TGF-β1:10 233±6 011비16 880±4 574,P<0.05혹P<0.01).결론 IgG、IgA、NF-κB、TGF-β1이상표체가능여DM간장、신장、폐장、심기、주동맥、시망막손해유관,면역화염증인소가능삼여기중, CsA가능통과하조IgG、IgA、NF-κB、TGF-β1표체,종이감경DM다기관개변.
    Objective To observe the pathological changes of liver, kidney, lung, myocardia, aorta and retina in rats with advanced diabetes mellitus (DM), and whether cyclosporine A (CsA) having the protective effects on the above organs.Methods Thirty male Wistar rats were randomly divided into CsA group, DM model group and normal control group (CON group) by random number table method, 10 rats in each group. Intra-peritoneal injection of streptozotocin (STZ) 55 mg/kg once was performed to prepare an advanced DM model. Forty-eight hours later, venous blood was collected from a tail vein and blood glucose was tested twice, and when the blood sugar was >16.7 mmol/L twice, the modeling was successful. All the rats were fed for 28 weeks, afterwards in CsA group, CsA 3 mg·kg-1·d-1 was given orally for 6 weeks, while in CON group, no treatment was applied. All the rats were sacrificed at 34 weeks after modeling, and the liver, kidney, lung, aorta, myocardium, retina were taken for hematoxylin-eosin (HE) stain and Masson stain to observe the pathological changes, and the expression levels of IgG, IgA, nuclear factor-κB (NF-κB) and transforming growth factor-β1 (TGF-β1) in the above organs were detected by the immunohistochemical staining and semi-quantitative analysis.Results There was 1 rat dead in DM model group and 2 rats dead in CsA group, therefore 9 rats in former group and 8 rats in latter group were included in the statistical analysis. ① HE staining: in the DM model group, there were hepatic lobular structural disorder, marked hypertrophy of glomerular volume, widening of alveolar septum, lymphocyte infiltration in the wall of aorta, hypertrophy of myocardia, arrangement disorder of retinal inner and outer nuclear layers, while the above changes in CsA group were milder compared with those in model group. ② Masson staining: in DM model group, there were scattered collagen deposition in hepatic lobules, significant increase of collagen in glomeruli and pulmonary interstitium, and increase of collagen in aorta and myocardia, but no marked positive reactions were seen in the retina; the above changes in CsA group were milder. ③ Immunohistochemical analyses showed: compared with CON group, the expressions of IgG, IgA, NF-κB, TGF-β1 in liver, kidney, lung, aorta, myocardia, retina were increased significantly in DM model group [all represented by average absorbance (A) values], while compared with DM model group, the expressions of these indexes were lower in CsA group (liver: IgA: 110 059±22 321 vs. 151 055±12 481, IgG: 106 265±39 225 vs. 158 296±65 723, NF-κB: 95 638±6 045 vs. 130 650±9 257, TGF-β1: 102 856±10 631 vs. 263 380±75 264; kidney: IgA: 37 305±8 340 vs. 53 281±5 412, IgG: 35 521±9 310 vs. 77 092±8 953, NF-κB: 37 768±2 622 vs. 54 888±2 494, TGF-β1: 48 425±1 170 vs. 62 687±8 593; lung: IgA: 94 022±1 701 vs. 198 977±38 135, IgG: 60 771±3 033 vs. 132 987±18 287, NF-κB: 100 900±49 842 vs. 156 153±25 756, TGF-β1: 132 330±42 627 vs. 177 707±21 156; aorta: IgA: 88 069±2 321 vs. 108 053±41 481, IgG: 109 260±35 328 vs. 178 792±56 763, NF-κB: 75 638±7 053 vs. 90 650±9 357, TGF-β1: 122 456±85 631 vs. 294 380±85 764; myocardia: IgA: 102 516±9 390 vs. 99 326±85 232, IgG: 86 528±12 650 vs. 194 226±68 473, NF-κB: 98 258±8 235 vs. 190 966±57 856, TGF-β1: 95 632±5 624 vs. 196 753±92 020; retina: IgA: 7 259±6 221 vs. 12 013±4 012, IgG: 10 660±9 328 vs. 16 592±6 163, NF-κB: 9 828±853 vs. 12 350±6 357, TGF-β1: 10 233±6 011 vs. 16 880±4 574,P < 0.05 orP < 0.01).Conclusion The abnormal expressions of IgG, IgA, NF-κB and TGF-β1 may be associated with damages of liver, kidneys, lungs, myocardia, aorta and retina in DM rats, in which immune and inflammatory factors are involved, CsA can ameliorate the pathological changes in DM multiple organs, and its mechanism is possibly related to the down-regulating the expressions of IgG, IgA, NF-κB and TGF-β1.
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