FKBP12.6敲除对小鼠逼尿肌过度活动的影响及其机制研究

周浩; 王珺; 姬广聚; 郑霁; 周占松

doi:10.16016/j.1000-5404.201907042

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FKBP12.6敲除对小鼠逼尿肌过度活动的影响及其机制研究

基础医学 | 更新时间：2026-01-09

- FKBP12.6敲除对小鼠逼尿肌过度活动的影响及其机制研究
- FK506 binding protein 12.6 knockout exacerbates detrusor overactivity in mice possibly by down-regulating ryanodine receptor 2
- 第三军医大学学报 2019年41卷第22期页码：2146-2151
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)第一附属医院全军泌尿外科研究所
  2.100020 北京，中国科学院生物物理研究所交叉科学所重点实验室
- 作者简介：
  
  [郑霁, E-mail:jizheng023@aliyun.comZHENG Ji, E-mail: jizheng023@aliyun.com
  [周占松, E-mail:zzs68754186@163.comZHOU Zhansong, E-mail: zzs68754186@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81770762)
- DOI：10.16016/j.1000-5404.201907042
  中图分类号： R322.62; R349-33; R694.52
- 收稿：2019-07-05，
  
  修回：2019-09-15，
  
  纸质出版：2019-11-30
- 稿件说明：
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周浩, 王珺, 姬广聚, 等. FKBP12.6敲除对小鼠逼尿肌过度活动的影响及其机制研究[J]. 第三军医大学学报, 2019,41(22):2146-2151.

Hao ZHOU, Jun WANG, Guangju JI, et al. FK506 binding protein 12.6 knockout exacerbates detrusor overactivity in mice possibly by down-regulating ryanodine receptor 2[J]. Journal of Third Military Medical University, 2019, 41(22): 2146-2151.
周浩, 王珺, 姬广聚, 等. FKBP12.6敲除对小鼠逼尿肌过度活动的影响及其机制研究[J]. 第三军医大学学报, 2019,41(22):2146-2151. DOI： 10.16016/j.1000-5404.201907042.

Hao ZHOU, Jun WANG, Guangju JI, et al. FK506 binding protein 12.6 knockout exacerbates detrusor overactivity in mice possibly by down-regulating ryanodine receptor 2[J]. Journal of Third Military Medical University, 2019, 41(22): 2146-2151. DOI： 10.16016/j.1000-5404.201907042.

摘要

目的

探讨他克莫司结合蛋白12.6(FK506 binding protein 12.6

FKBP12.6)敲除对小鼠逼尿肌过度活动(detrusor overactivity

DO)的影响及其作用机制。

方法

8~10周龄129系雌性野生型(WT组)和FKBP12.6基因敲除小鼠(纯合子

KO组)各30只，通过膀胱出口部分梗阻(partial bladder outlet obstruction

PBOO)建立小鼠DO模型。HE染色观察2组小鼠膀胱逼尿肌形态，尿斑实验(3 h内小鼠的排尿情况)比较尿频症状，尿动力学实验比较储尿末期膀胱压力变化情况，腹腔脏器充盈反应(visceromotor responses

VMRs)及膀胱平滑肌充盈期电活动比较膀胱对压力的反应情况，膀胱平滑肌肌条自发性收缩实验判断其对张力的敏感性，Western blot比较雷尼丁受体2(Ryanodine Receptor 2

RyR2)表达的变化。

结果

FKBP12.6敲除不会使小鼠逼尿肌形态发生明显的改变，但能加重小鼠尿频症状:与WT组比较，KO组排尿次数明显增多[(43.500±19.164)

(22.000±14.717)次/3 h

0.05

]

；使DO模型鼠储尿末期DO程度更加严重:与WT组比较

KO组储尿期膀胱压力的波动次数明显增加[(13.900±5.430)

(8.000±3.232)次/30 min

0.05

]

；并使小鼠逼尿肌条对张力的敏感性增高(3.200±0.648

1.200±0.245

0.01)。与WT组比较，FKBP12.6敲除小鼠RyR2表达出现明显下调(0.154±0.106

1.000±0.444

0.01)。

结论

FKBP12.6基因敲除可能通过下调RyR2导致小鼠DO程度加重。

Abstract

Objective

To investigate the effect of FK506 binding protein 12.6 (FKBP12.6) knockout on detrusor overactivity (DO) in mice and explore the possible mechanism.

Methods

Mouse models of DO were established by partial bladder outlet obstruction (PBOO) in 30 wild-type mice (WT) and 30 homozygote FKBP12.6 knockout mice (KO group). All the mice were 8-10 weeks old and female. The morphology of the detrusor was observed using HE staining

and void spots and urodynamic test were used to assess the changes in the symptom of frequent urinary and the bladder pressure

respectively. Visceromotor responses (VMRs) and bladder smooth muscle electrical activity in the filling stage were recorded to assess the bladder response to pressure. Spontaneous contraction of the detrusor strips was tested to evaluate the sensitivity of the detrusor to tension

and the expression of ryanodine receptor 2 (RyR2) was detected using Western blotting.

Results

FKBP12.6 knockout did not cause obvious changes in detrusor morphology

but aggravated the symptom of frequent urination in the mice. Compared with WT mice

the mice in KO group showed a significantly increased micturition frequency (43.500±19.164

22.000±14.717 every 3 h

0.05) with aggravated DO

significantly increased fluctuation fr

equency of bladder pressure during the urine storage period (13.900±5.430

8.000±3.232 per 30 min

0.05)

and significantly increased sensitivity of the detrusors to tension (3.200±0.648

1.200±0.245

0.01). RyR2 expression in the detrusors decreased significantly in FKBP12.6 knockout mice as compared with the WT mice (0.154±0.106

1.000±0.444

0.01).

Conclusion

FKBP12.6 knockout results in aggravation of DO in mouse models possibly by down-regulation of RyR2 in the detrusors.

关键词

Keywords

references

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