Piculo Fernanda, Marini Gabriela, Barbosa Angélica Mércia Pascon, Damasceno Débora Cristina, Matheus Selma Maria Michelin, Felisbino Sérgio Luis, Daneshgari Firouz, Rudge Marilza Vieira Cunha
Laboratory of Experimental Research on Gynecology and Obstetrics, Department of Gynecology and Obstetrics, Botucatu Medical School, Universidade Estadual Paulista-UNESP, Botucatu, São Paulo, Brazil.
Int Urogynecol J. 2014 Mar;25(3):403-15. doi: 10.1007/s00192-013-2218-4. Epub 2013 Sep 17.
Diabetes mellitus (DM) during pregnancy is associated with high levels of urinary incontinence (UI) and pelvic floor muscle dysfunction. Mild DM can lead to changes in urethral striated muscle and extracellular matrix (ECM) in pregnant rats considering both structures as an entire system responsible for urinary continence.
Ninety-two female Wistar rats were distributed in four experimental groups: virgin, pregnant, diabetic, and diabetic pregnant. In adult life, parental nondiabetic female rats were mated with nondiabetic male rats to obtain newborns. At the first day of birth, newborns received citrate buffer (nondiabetic group) or streptozotocin 100 mg/kg body weight, subcutaneous route (mild DM group). At day 21 of the pregnancy, the rats were lethally anesthetized and the urethra and vagina were extracted as a unit. Urethral and vaginal sections were cut and analyzed by: (a) cytochemical staining for ECM and muscle structural components, (b) immunohistochemistry to identify fast- and slow-muscle fibers, and (c) transmission electron microscopy for ultrastructural analysis of urethral striated muscle.
In comparison with the three control groups, variations in the urethral striated muscle and ECM from diabetic pregnant rats were observed including thinning, atrophy, fibrosis, increased area of blood vessels, mitochondria accumulation, increased lipid droplets, glycogen granules associated with colocalization of fast and slow fibers, and a steady decrease in the proportion of fast to slow fibers.
Mild DM and pregnancy can lead to a time-dependent disorder and tissue remodeling in which the urethral striated muscle and ECM has a fundamental function.
妊娠期糖尿病(DM)与高尿失禁(UI)水平及盆底肌肉功能障碍相关。考虑到尿道横纹肌和细胞外基质(ECM)作为一个负责尿失禁的完整系统,轻度糖尿病可导致妊娠大鼠尿道横纹肌和细胞外基质发生变化。
92只雌性Wistar大鼠分为四个实验组:未孕、妊娠、糖尿病、糖尿病妊娠组。成年后,将亲代非糖尿病雌性大鼠与非糖尿病雄性大鼠交配以获得新生大鼠。出生第一天,新生大鼠接受柠檬酸盐缓冲液(非糖尿病组)或100mg/kg体重链脲佐菌素皮下注射(轻度糖尿病组)。妊娠第21天,将大鼠深度麻醉,将尿道和阴道作为一个整体取出。将尿道和阴道切片进行如下分析:(a)对细胞外基质和肌肉结构成分进行细胞化学染色,(b)通过免疫组织化学鉴定快肌纤维和慢肌纤维,(c)通过透射电子显微镜对尿道横纹肌进行超微结构分析。
与三个对照组相比,观察到糖尿病妊娠大鼠尿道横纹肌和细胞外基质存在变化,包括变薄、萎缩、纤维化、血管面积增加、线粒体聚集、脂滴增多、糖原颗粒与快慢纤维共定位,以及快纤维与慢纤维比例持续下降。
轻度糖尿病和妊娠可导致一种时间依赖性紊乱和组织重塑,其中尿道横纹肌和细胞外基质具有重要作用。