大鼠控尿功能的性别差异及其与尿道横纹括约肌MyHCIs的相关性研究
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摘要
目的比较雌雄两种性别Fisher344大鼠控尿功能的差异,观察两种性别大鼠尿道的大体解剖和组织成分的异同,以及肌球蛋白重链同源分子(MyHCIs)各亚型在大鼠尿道横纹肌中的分布及表达随性别年龄变化的规律,探索雌雄两种大鼠控尿功能差异的形态学和分子学基础。
     方法应用尿动力学方法检测Fisher344大鼠控尿功能的性别年龄差异;通过免疫组化染色和Masson’s Trichrome染色法检测大鼠尿道结构、组织学构成成分,及横纹肌MyHCIs分布性别年龄差异;通过实时定量PCR和Western Blot检测大鼠尿道横纹括约肌MyHCIs基因表达的性别年龄差异。
     结果尿动力学检查发现雌雄两种性别大鼠的漏尿点压力均表现为随年龄增加显著降低的规律,雌性大鼠漏尿点压力低于雄性,且此差异随增龄变化逐渐显著。形态学检查发现雌雄两性大鼠均存在形态相似的尿道横纹括约肌结构,大鼠横纹肌含量及横纹肌中MyHCIsⅡ型含量随年龄增高而降低,雌性含量低于雄性,且此差异随增龄变化逐渐显著。分子生物学检测提示MyHCIsⅡb及Ⅱx亚型表达随年龄增加显著降低,雌性表达低于雄性,且此差异随增龄变化逐渐显著。
    
     结论大鼠控尿功能随增龄变化而下降,雌性大鼠控尿功能较雄性为差,可能与雌性大鼠尿道横纹括约肌总容量较雄性为少,MyHCIsⅡ型,特别是Ⅱb及Ⅱx亚型表达明显少于雄性大鼠相关。
Objective Based upon morphology studies, female gender and elder age are riskfactors for developing stress urinary incontinence, however, the mechanism is not entirelyclear.The aim of this study was to describe the differences in urinary continence functionbetween the female and male rats, to measure the differences in sphincter muscle betweenthe two genders, and to investigate the myosin heavy chain isoforms (MHCIs) expression inthe urethral striated sphincter of rat to discuss the mechanism which may exist. Materialsand Methods Totally16female and16male adult Fisher rats at different ages were dividedinto8groups,group Ⅰ (6months,female), group Ⅱ (12months,female),groupⅢ (24months,female), group Ⅳ (32months,female), group Ⅴ(6months,male),group Ⅵ(12months,male),group Ⅶ(24months,male) and group Ⅷ(32months,male). We had tested the continence function, described the anatomy of urethra andexamined the muscle fiber distribution (by Masson’s Trichrome stain) as well as theexpression of the corresponding MHCIs protein and messenger RNA (mRNA)(protein andmRNA expression, using Western blot or quantitative real-time polymerase chain reaction(RT-PCR)).Results The significant differences in urinary continence function were notebetween the female and male rats, with female rats having marked lower abdominal leakpoint pressure and marked faster decrease of abdominal leak point pressure in female ratswith aging. Female rats were noted having less volume of striated muscle than male rats.The outcome revealed that the urethral striated muscles consist of four kind of isoforms:MyHC-Ⅰ,MyHC-Ⅱa, MyHC-Ⅱb and MyHC-Ⅱx. Comparing with the male rats, theexpression of fast MHC, especially MyHC-Ⅱb and MyHC-Ⅱx in female rats was lowerthan those in male, while the slow MHC shows opposite at the same time. Conclusions:Gender-related differences were noted in urinary continence function in rats as evaluated with urodynamic studies. The male rats demonstrated better continence function thanfemales. The higher expression of MyHC-Ⅱb and MyHC-Ⅱx in the males urethral striatedsphincter muscles might be the molecular basis responsible for the gender-relateddifferences in continence function.
引文
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    8. Keane DP, O'Sullivan S. Urinary incontinence: anatomy, physiology andpathophysiology. Baillieres Best Pract Res Clin Obstet Gynaecol.2000Apr;14(2):207-26.
    9. Kim K, et al. Mechanisms of female urinary continence under stress: frequencyspectrum analysis.J Biomech.2001May;34(5):687-91.
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