CAJ | 학술논문

目的观察重组腺相关病毒(rAAV)介导大鼠胰岛素样生长因子-1(IGF-1)基因对糖尿病大鼠膀胱病变的治疗作用.方法将40只雄性SD大鼠随机分成正常组(CN组)、糖尿病组(DM组)、转导rAAV2/1-IGF-1组(IGF-1组)、胰岛素治疗组(INS组)和转导rAAV2/1-IGF-1+胰岛素治疗组(IGF-1+ INS组).链脲佐菌素(STZ)诱导糖尿病8周后各组分别或同时每只给予胰岛素6 IU/d和/或rAAV2/1-IGF-1 100 μl/d.基因转导6周后尿流动力学评估膀胱功能,苏木素-伊红(HE)染色观察膀胱逼尿肌的变化并检测膀胱IGF-1的表达水平.结果与DM组比较,IGF-1+INS组、INS组和IGF-1组排尿效率均较DM组显著增加(86.59±1.20、79.18±1.34、77.88±1.82比76.16±1.87).DM组膀胱逼尿肌可见肌束排列紊乱松散、肌束断裂.IGF-1组和INS组膀胱逼尿肌损伤程度均明显减轻,IGF-1+ INS组膀胱逼尿肌结构表现接近正常.膀胱IGF-1表达水平免疫组织化学评分DM组(3.37±0.52)较IGF-1+ INS组(4.16±0.15)、INS组(4.08±0.30)和IGF-1组(4.12±0.35)显著降低(P＜0.05).结论糖尿病大鼠膀胱IGF-1表达水平降低可能参与糖尿病膀胱病变(DCP)的发生与发展,IGF-1基因和INS治疗可部分修复膀胱功能.
목적 관찰중조선상관병독(rAAV)개도대서이도소양생장인자-1(IGF-1)기인대당뇨병대서방광병변적치료작용.방법 장40지웅성SD대서수궤분성정상조(CN조)、당뇨병조(DM조)、전도rAAV2/1-IGF-1조(IGF-1조)、이도소치료조(INS조)화전도rAAV2/1-IGF-1+이도소치료조(IGF-1+ INS조).련뇨좌균소(STZ)유도당뇨병8주후각조분별혹동시매지급여이도소6 IU/d화/혹rAAV2/1-IGF-1 100 μl/d.기인전도6주후뇨류동역학평고방광공능,소목소-이홍(HE)염색관찰방광핍뇨기적변화병검측방광IGF-1적표체수평.결과 여DM조비교,IGF-1+INS조、INS조화IGF-1조배뇨효솔균교DM조현저증가(86.59±1.20、79.18±1.34、77.88±1.82비76.16±1.87).DM조방광핍뇨기가견기속배렬문란송산、기속단렬.IGF-1조화INS조방광핍뇨기손상정도균명현감경,IGF-1+ INS조방광핍뇨기결구표현접근정상.방광IGF-1표체수평면역조직화학평분DM조(3.37±0.52)교IGF-1+ INS조(4.16±0.15)、INS조(4.08±0.30)화IGF-1조(4.12±0.35)현저강저(P＜0.05).결론 당뇨병대서방광IGF-1표체수평강저가능삼여당뇨병방광병변(DCP)적발생여발전,IGF-1기인화INS치료가부분수복방광공능.
Objective To study the curative treatment role of the recombinant adeno-associated virus (rAAV)-mediated rat insulin-like growth factor-1 (IGF-1) gene on streptozotocin-induced diabetic cystopathy.Methods Forty male SD rats were divided randomly into five age-matched groups:normal control (CN,n =8),diabetes model (DM,n =8),rAAV2/1-IGF-1 transduction model (IGF-1,n =8),insulin therapy model (INS,n =8),rAAV2/1-IGF-1 transduction & insulin therapy model group (IGF-1 + INS,n =8).Eight weeks after the induction of diabetes model,insulin (6 U) and/or rAAV2/1-IGF-1 (100 μ1) was injected into rats of corresponding groups.Urinary dynamics was analyzed to evaluate the bladder function after gene therapy for 6 weeks.HE staining was used to observe the pathological changes of bladder detrusor.The expression profile of IGF-1 protein was assessed by using immunohistochemistry (IHC).Results As compared with DM group,the voiding rate in IGF-1 + INS group,INS group and IGF-1 group was significantly increased (86.59 ± 1.20,79.18 ± 1.34,77.88 ± 1.82 vs.76.16 ± 1.87,P ＜ 0.05).Detrusor muscle in DM group showed bundles derangement,loose structure,but detrusor injury severity in IGF-1 group and INS group was significantly relieved,and detusor structure performance inIGF-1 + INS group was close to the normal level.The IGF-1 expression level in bladder tissue was significantly decreased in DM group (3.37 ± 0.52) as compared with IGF-1 + INS group (4.16 ± 0.15),INS group (4.08 ± 0.30) and IGF-1 group (4.12 ± 0.35).Conclusion The decreased IGF-1 expression levels in bladder tissue may be involved in the development of diabetic cystopathy.IGF-1 gene and INS treatment may play a part role in repairing bladder function of diabetic rats.