高脂血症对雄性兔膀胱功能的影响及其可能机制  

Effects of diabetic hyperlipidemia on bladder function and its possible mechanisms in a male rabbit model

作　　者：刘希高[1] 唐渊[2] 虞巍[2] 吴士良[2] 金杰[2] 

机构地区：[1]山东大学齐鲁医院泌尿外科,济南250012 [2]北京大学第一医院泌尿外科暨北京大学泌尿外科研究所

出　　处：《中华医学杂志》2013年第42期3338-3342,共5页National Medical Journal of China

摘　　要：目的 单纯高脂饲料饲养雄性新西兰兔建立高脂血症动物模型,研究高脂血症对膀胱功能、形态学的影响及可能机制.方法 选取体重2.5～3.0 kg成年雄性新西兰兔30只,依次编号后采用随机抽签法随机分成高脂饲料（高脂组）及普通饲料（对照组）两组,分别进行在体膀胱尿动力学检查及离体逼尿肌肌条张力实验评估膀胱功能,HE染色观察膀胱壁及髂内动脉形态变化,透射电镜下观察膀胱逼尿肌肌细胞微结构变化,以及免疫组织化学方法确定膀胱逼尿肌及黏膜层胆碱能（M）2、3受体表达情况.结果 喂养至第12周时,高脂组（n=14）在体膀胱尿动力学检查显示储尿期膀胱逼尿肌不自主收缩增加者高于对照组（n=13）（10/14比1/13,P〈0.05）、顺应性变差[（2.16±0.17） 比（4.18±0.21） ml/cm H2O,P〈0.01];高脂组逼尿肌离体肌条在M受体激动剂卡巴胆碱刺激下收缩力减弱;在选择性M3受体拮抗剂索利那新作用下肌条张力下降幅度更明显.HE染色示高脂组髂内动脉内膜增厚;膀胱平滑肌层肌纤维排列紊乱且其间纤维结缔组织增加,透射电镜发现高脂组膀胱逼尿肌胞质内线粒体肿胀改变;免疫组织化学半定量结果显示M2受体在两组中差异无统计学意义（P〉0.05）,M3受体在高脂组中表达高于对照组（膀胱黏膜层：146±14 比108±9,P〈0.01;膀胱平滑肌层：131±17比116±15,P〈0.05）,且在黏膜层表达增加更为明显.结论 高脂血症雄性新西兰兔出现顺应性变差、不自主收缩次数增多及收缩力减弱等膀胱功能改变,考虑可能与高脂血症引起的膀胱慢性缺血和膀胱黏膜层和肌层M3受体表达增加有关.Objective To evaluate the effects of chronic hyperlipidemia on bladder function and its possible mechanisms and examine the functional and histological changes of bladder in a diabetic hyperlipidemie model. Methods A total of 30 male New Zealand white rabbits （ 2. 5 to 3.0 kg） were numbered sequentially and randomly divided into 2 groups （ hyperlipidemic group and control group）. Then urodynamie test and detrusor strip contraction study were performed to assess bladder function. Histological studies of bladder and internal iliae arteries were performed with hematoxylin and eosin staining. The ultrastrueture of bladder detrnsor tissue was examined by transmission electron microscopy. Also the bladder tissue M2, 3-muscarinie receptor protein levels were examined by immunohistochemistry. Results After 12 weeks, the urodynamic test of the test group showed significantly increased non-voiding contractions（ 10/14 vs 1/13, P 〈0. 05） and deereased compliance（ （2. 16 ±0. 17） vs （4. 18 ±0. 21 ） mt/em H2O, P 〈0. 01 ） versus the control group. The functional experiments showed that carbachol-induced contractions significantly decreased in hyperlipidemie rabbits than those in controls. As to the relaxant actions of selective muscarinic receptor M3 antagonist solifenaein, the bladder strips of hyperlipidemie rabbits were significantly more sensitive than those of the controls. Histological examination showed thickened intima of internal iliac arteries, urothelial disruption and mild fibrosis in the hyperlipidemie rabbits. Transmission electron microscopy of hyperlipidemic bladder muscle tissues showed swollen mitochondrial damage. As to the immunohistochemical results, compared with the control group, the hyperlipidemic group showed significantly increased M3 receptor expression both in bladder urothelium （ 146 ± 14 vs 108 ± 9 ,P 〈 0.0! ） and smooth muscle layer （ 131 ± 17 vs 116 ± 15, P 〈 0. 05 ）. And the expression was more obvious in urothelium layer. Conclusions Involuntary det

关 键 词：高脂血症 膀胱 受体 毒蕈碱 

分 类 号：R589.2[医药卫生—内分泌]