压力性尿失禁动物模型尿道功能和盆底肌力的比较

目的:比较不同压力性尿失禁(stress urinary incontinence,SUI)动物模型在尿流动力学和盆底肌力方面的差异,以寻求最能模拟SUI的动物模型。方法:取64只大鼠随机均分为阴道扩张模型组(vaginal distension,VD)和阴部神经压榨模型组(pudendal nerve crush,PNC)和阴部神经切断模型组(pudendal nerve transection,PNT)以及VD+PNC造模组4组,每组16只,另取4只大鼠作为正常对照组。造模后第2天,所有大鼠行喷嚏试验。造模后第4天、第10天、3周、6周,测定尿流动力学和盆底肌力。正常对照组大鼠在喷嚏试验后进行尿流动力学和盆底肌力测定。结果:喷嚏实验结果显示正常对照组未观察到阳性大鼠(0/4),各模型组喷嚏试验结果阳性率均显著高于正常对照组(P0.05)。动力学检测显示:与正常组(40.3±3.4 cm H_2O)相比,VD组在造模后4d的LPP值显著降低(P0.05),而造模后10d、3周和6周时的LPP值无统计学差异(P0.05);PNC组和PNC+VD组在造模后4d、10d、3周时的LPP值均显著降低(P0.05),而在造模后6周时无统计学差异(P0.05);PNT组在造模后4d、10d、3周和6周时的LPP值均显著降低(P0.05)。最大膀胱容量测定显示:与正常组(2.42±0.12 mL)相比,VD组在造模后10d的MBC值显著降低(P0.05),而造模后4d、3周和6周时无统计学差异(P0.05);PNC组在造模后10d、3周时显著降低(P0.05),而在造模后4d和6周时无统计学差异(P0.05);PNC+VD组和PNT组在造模后10d及3周和6周时均显著降低(P0.05),而在造模后4d时无统计学差异(P0.05)。盆底肌力测定结果显示:与正常组的耻尾肌肌力值(2.71±0.12 g/g)相比,VD组在造模后10d显著降低(P0.05),而造模后4d、3周和6周时无统计学差异(P0.05);PNC组在造模后10d、3周时显著降低(P0.05),而在造模后4d和6周时无统计学差异(P0.05);PNC+VD组和PNT在造模后10d及3周和6周时均显著降低(P0.05),而在造模后4d时无统计学差异(P0.05)。结论:VD、PNC、VD+PNC和PNT造模均能有效模拟出SUI发病中的盆底神经和肌肉损伤。其中,VD造模主要引起盆底肌的直接损伤,但其恢复较快。PNC和PNT造模则能损伤阴部神经并间接地造成盆底肌的失神经性萎缩,但PNT所造成的损伤较难恢复,不能有效地模拟SUI的自然修复过程。而VD+PNC造模则兼具VD和PNC两种造模方法的特点,能从多个层面模拟SUI的发病。因此,在实践中应根据实验研究的层面采用合适的动物模型。

Comparison of the Urethral Function and Pelvic Floor Muscle Strength in Animal Models of Stress Urinary Incontinence

ABSTRACT Objective: To compare the differences of urinary dynamics and pelvic floor muscle strength between different SUI models and find the best animal model for simulating SUI. Methods: 64 rats were randomly divided into VD(vaginal distension) group, PNC(pudendal nerve crush) group, VD+PNC group and PNT (pudendal nerve transection) group averagely, and another 4 rats served as the control group. After animal models were established, all rats were subjected to sneezing test on the second day after modeling, and then 4 rats were selected from each group at fourth, tenth, 3 and 6 weeks after modeling to measure urine flow dynamics and pelvic floor muscle strength. Results: Sneezing test showed no positive rat in control group (0/4), the positive rate of sneezing test in model groups were all significantly higher than that of the control group, but there was no statistical difference between the model groups(P>0.05). According to urodynamic examination, when comparing with normal group (LPP = 40.3 + 3.4 cm H2O), the LPP values at 4d after modeling of VD group was statistically different (P < 0.05), while no significant difference (P > 0.05) was found at 10d, 3 weeks and 6 weeks after modeling. There was significant differencesin the PNC group at 4d, 10d, 3 weeks after modeling(P<0.05), with no significant difference was found at 6 weeks after modeling (P > 0.05). The LPP values in PNC+VD group at 4d, 10d and 3 weeks were statistically different (P < 0.05), with no significant difference in 6 weeks after modeling (P > 0.05). The LPP values in PNT group at 4d, 10d, 3 weeks and 6 weeks after modeling were statistically different (P < 0.05). The maximum bladder capacity (MBC) determination showed that, when comparing with the normal group (2.42±0.12 mL, MBC values in VD group at 10d after modeling were statistically different (P < 0.05), with no significant difference at 4d, 3 weeks and 6 weeks after modeling (P > 0.05). There were significant differences in PNC group at 10d and 3 weeks (P < 0.05), with no significant difference at 4d and 6 weeks after modeling (P > 0.05). There were significant differences in PNC+VD group at 10d and 3 and 6 weeks (P < 0.05), with no significant difference at 4d after modeling (P > 0.05). There were significant differences in PNT group at 10d and 3 and 6 weeks (P < 0.05), with no significant difference at 4d after modeling (P > 0.05). The pelvic floor muscle strength measurement showed that pelvic muscle strength of the pubococcygeus in normal group was 2.71 + 0.12 g/g. There was significant difference in VD group at 10d after modeling (P < 0.05), with no significant difference at 4d, 3 and 6 weeks after modeling (P > 0.05). There were significant differences in PNC group at 10d and 3 weeks after modeling (P < 0.05), with no significant difference at 4d and 6 weeks after modeling (P > 0.05). In PNC+VD group, there were significant differences at 10d and 3 and 6 weeks (P < 0.05), but there was no difference at 4d after modeling (P > 0.05). In PNT group, there were significant differences at 10d, 3 and 6 weeks after modeling (P < 0.05), with no significant difference at 4d after modeling (P > 0.05). Conclusion: VD, PNC, VD+PNC and PNT models can effectively simulate the injury of pelvic floor nerves and muscles of SUI. The VD model mainly directly caused the injury of pelvic floor muscle, and can recover very soon. Both PNC and PNT models can damage the pudendal nerve and indirectly cause the denervated atrophy of pelvic floor muscle, but the damage caused by PNT is difficult to recover which may not effectively simulate the natural repair process of SUI. However, VD+PNC model has the characteristics of both VD and PNC which may simulate the onset of SUI from multiple levels. Therefore, corresponding animal models can be selected according to the experimental design.