腺相关病毒介导胰岛素样生长因子-1对糖尿病大鼠膀胱病变的治疗作用  

Adeno-associated virus-mediated insulin-like growth factor-1 in the treatment of diabetic cystopathy

作　　者：何朝辉[1] 曹石金[2] 潘卫兵[2] 李逊[3] 何永忠[3] 鲁雄兵[4] 

机构地区：[1]广州医学院第一附属医院微创外科中心泌尿外科广东省泌尿外科重点实验室,510230 [2]深圳市坪山新区人民医院泌尿外科 [3]广州医学院第五附属医院泌尿外科 [4]南昌大学第二附属医院泌尿外科

出　　处：《中华实验外科杂志》2013年第6期1157-1160,共4页Chinese Journal of Experimental Surgery

基　　金：基金项目：国家自然科学基金资助项目（30860297）;广东省A然科学基金资助项目（06022697、$2011040003691）;广州市医药卫生科技计划资助项目（201102A213130）;广州医学院博士启动项目[广医科（2010）1号];深圳市坪山新区卫生发展孵化基金资助项目（201206）;广州市教育局资助项目（2012C065）

摘　　要：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6IU／d和／或rAAV2／1-IGF-1100pJ／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一1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。Objective To study the curative treatment role of the recombinant adeno-associated vi- rus （rAAV）-mediated rat insulin-like growth factor-1 （IGF-1） gene on streptozotoein-indueed diabetic cys- topathy. 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 p,l） 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 inju- ry severity in IGF-1 group and INS group was significantly relieved, and detusor structure performance in IGF-1 ＋ INS group was close to the normal level. The IGF-1 expression level in bladder tissue was signifi- cantly 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-I 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 treat- ment may play a part role in repairing bladder function of diabetic rats.

关 键 词：腺相关病毒 胰岛素样生长因子-1 糖尿病 膀胱病变 

分 类 号：R6[医药卫生—外科学] R587[医药卫生—临床医学]