Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2016, Vol. 12 ›› Issue (05): 540 -546. doi: 10.3877/cma.j.issn.1673-5250.2016.05.010

Special Issue:

Original Article

Establishment and evaluation of mouse model of stress urinary incontinence

Jianming Tang1, Li Hong1,(), Cheng Liu1, Yang Li1, Qing Yang1, Jie Min1, Shasha Hong1   

  1. 1. Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
  • Received:2016-01-20 Revised:2016-08-29 Published:2016-10-01
  • Corresponding author: Li Hong
  • About author:
    Corresponding author: Hong Li, Email:
Objective

To explore the feasibility of building a stable mouse model of stress urinary incontinence (SUI) by vaginal dilation (VD) method.

Methods

From October to December 2015, a total of 135 cases of 8-week-old female C57BL/6 mice were selected as research subjects. They were randomly divided into VD 1, 3, 7, 14 and 28 d group (15 cases of mice in each group) and control group (60 cases of mice). The mouse model of SUI in VD 1, 3, 7, 14 and 28 d group was built by VD method, and the maximum bladder capacity (MBC), bladder leak point pressure (BLPP) and abdomen leak point pressure (ALPP) were detected in 1, 3, 7, 14 and 28 d after VD, respectively. The mice in control group didn′t receive any treatment and their MBC, BLPP and ALPP were detected directly. The normal reference ranges of MBC, BLPP and ALPP in control group were estimated by ±1.96 s, and they were used to analyzed the successful modeling rate and the SUI model durability of all VD groups. The expression of matrix metalloproteinases (MMP)-2 and -9 in paries anterior vagina of mice in every group was detected by gelatin zymography method. MBC, BLPP, ALPP, MMP-2 and -9 in all VD groups and control group were statistically analyzed. All experimental protocols were approved by the Institutional Animal Care and Use Committee. There were no statistical differences in weight and week-old between all groups of mice (P>0.05).

Results

①Single factor analysis of variance results showed that there were significant differences between all VD groups and control group in MBC, BLPP and ALPP (F=11.060, P=0.000; F=71.670, P=0.000; F=61.120, P=0.000). The MBC, BLPP and ALPP in VD 1, 3 and 7 d group were significantly decreased compared with those in control group, and all the differences were statistically significant (MBC: tD=7.115, 4.528, 3.909; all P=0.000. BLPP: tD=18.461, 15.949, 14.294; all P=0.000; ALPP: tD=16.198, 12.895, 12.700; all P=0.000). Compared with control group, the BLPP and ALPP were significantly decreased in VD 14 and 28 d group, and all the differences were statistically significant (BLPP: tD=7.494, 3.104; P=0.000, 0.003. ALPP: tD=6.356, 2.031; P=0.000, 0.046), however, there were no significant differences in MBC (tD=1.086, 0.469; P=0.293, 0.640). ②The normal reference range of C57BL/6 mice′s MBC was 0.06-0.15 mL, BLPP was 34.55-53.81 cmH2O (1 cmH2O=0.098 kPa) and ALPP was 33.88-58.96 cmH2O. ③The successful modeling rates in VD 1 and 3 d group both were > 93%, and about 90%, 60% and 30% in VD 7, 14, 28 d group, respectively. The SUI model durability was 2 to 4 weeks. ④Single factor analysis of variance results showed that there were significant differences between all VD groups and control group in MPP-2 and -9 (F=55.130, P=0.000; F=18.850, P=0.000). Compared with control group, the expression of MMP-2 and -9 in paries anterior vagina of VD 3, 7 and 14 d group were significantly increased (MMP-2: t=5.257, 17.280, 11.620; P=0.006, 0.000, 0.000. MMP-9: t=2.953, 9.538, 5.450; P=0.042, 0.001, 0.006). However, there were no differences in VD 1 and 28 d group compared with control group (MMP-2: t=0.004, 2.360; P=0.997, 0.078. MMP-9: t=0.245, 2.156, P=0.818, 0.097). The expressions of MMP-2 and -9 in VD 7 d group both were the highest, and there were significant differences compared with VD 3 and 14 d group (MMP-2: t=7.733, 6.526; P=0.002, 0.003. MMP-9: t=5.468, 6.257, P=0.005, 0.003).

Conclusions

The durability of VD mouse model of SUI is 2 to 4 weeks, the SUI mouse model within 3 to 7 days after its building by VD method is the most stable and reliable subject to research the pathogenesis and therapy of SUI. Comprehensively analyzing the parameters of urinary dynamics and the effectiveness of SUI model are better and more reliable than just analyzing the parameters of urinary dynamics. Because of the small sample size in this study and the influence of different operational capabilities of different operators and many other uncontrollable factors, the normal reference ranges of MBC, BLPP and ALPP and the effectiveness of SUI model should be confirmed by further researches.

图1 各组小鼠尿动力学检测结果比较(图1A:各组小鼠MBC检测结果比较;图1B:各组小鼠BLPP检测结果比较;图1C:各组小鼠ALPP检测结果比较)
表1 对照组(n=60) C57BL/6小鼠尿动力学指标的正常参考值范围
表2 VD 1、3、7、14及28 d组小鼠压力性尿失禁建模成功率[鼠数(%)]
图2 各组小鼠阴道前壁组织MMP-2和-9明胶酶谱法检测结果比较(图2A:各组小鼠阴道前壁组织MMP-2和-9明胶酶谱条带图; 图2B:各组小鼠阴道前壁组织MMP-2和-9明胶酶谱量化分析图)
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