400037 重庆,陆军军医大学(第三军医大学)第二附属医院泌尿外科
Received:26 August 2020,
Revised:2020-10-27,
Published:15 February 2021
移动端阅览
Yang YANG, Hengshuai ZHANG, Qudong LU, et al. Role of P2X3 receptor in dorsal root ganglion in colitis-induced bladder overactivity[J]. Journal of Third Military Medical University, 2021, 43(3): 195-201.
Yang YANG, Hengshuai ZHANG, Qudong LU, et al. Role of P2X3 receptor in dorsal root ganglion in colitis-induced bladder overactivity[J]. Journal of Third Military Medical University, 2021, 43(3): 195-201. DOI: 10.16016/j.1000-5404.202008206.
目的
2
通过三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)灌肠方式建立大鼠结肠炎模型,探讨背根神经节(dorsal root ganglion
DRG)中P2X3受体在结肠炎诱导的膀胱排尿功能障碍中的作用。
方法
2
按随机数字表法将雌性SD大鼠分为3组:对照组、TNBS-3d组和TNBS-7d组。对照组用生理盐水灌肠,后2组分别用50% TNBS乙醇溶液(100 mg/kg)诱导大鼠结肠炎,灌肠3 d或7 d后采用HE染色或尼氏染色分别观察大鼠结肠和膀胱的组织病理变化,应用膀胱测压技术检测大鼠膀胱的排尿功能,免疫荧光染色检测DRG中P2X3受体的表达情况,鞘内注射P2X3抑制剂A-317491观察P2X3受体在结肠诱导的膀胱排尿功能障碍中的作用。
结果
2
TNBS诱导结肠炎后,大鼠结肠表现出黏膜充血水肿,炎性细胞浸润。大鼠膀胱未见明显组织病理学改变,但肥大细胞浸润增多。与对照组相比,TNBS-3d组的大鼠表现出明显的膀胱过度活动,其中膀胱排尿间隔缩短(
P
<
0.01)和最大排尿压增加(
P
<
0.01)。与对照组相比,TNBS-7d组的大鼠主要表现为膀胱排尿间隔缩短(
P
<
0.01),最大排尿压无明显变化。与对照组相比,TNBS-3d组和TNBS-7d组的大鼠DRG中P2X3阳性神经元数量均明显增加(
P
<
0.01),鞘内注射A-317491能显著延长TNBS-3d组和TNBS-7d组大鼠的膀胱排尿间隔(
P
<
0.01),同时显著降低TNBS-3d组大鼠的最大排尿压(
P
<
0.05),但TNBS-7d组大鼠的最大排尿压无明显影响。
结论
2
DRG中P2X3受体在结肠炎诱导的膀胱过度活动起着重要作用,鞘内注射P2X3抑制剂能明显改善膀胱的排尿功能障碍。
Objective
2
To investigate the role of P2X3 receptor in dorsal root ganglion (DRG) in bladder micturition function due to colitis-induced bladder dysfunction in the rat model of 2
4
6-trinitrosulfonic acid (TNBS)-induced colitis.
Methods
2
Female SD rats were randomly divided into control group
TNBS-3d and TNBS-7d groups. The rat model of colitis was induced with 50% TNBS ethanol solution (100 mg/kg) by clyster
and the rats from the control group were clystered by isopyknic normal saline. In 3 or 7 d after clyster
the colon and bladder tissue of rats were collected for HE staining and Nissl Staining. Cystometry was performed to observe the bladder micturition function. Immunofluorescence staining was carried out to detect the expression of P2X3 receptor in DRG. The effect of P2X3 on colitis-induced bladder dysfunction was observed by intrathecal injection of P2X3 receptor inhibitor A-317491.
Results
2
The colons of TNBS-induced colitis rats showed mucosal hyperemia and edema and inflammatory cell infiltration. There were no histopathological changes in the bladder among the 3 groups. Compared to the control group
there were larger number of mast cells observed in the bladder from the TNBS-3d and TNBS-7d groups. The results of cystometry showed that the intercontractile interval of bladder (ICI) was significantly decreased and maximum bladder pressure (MBP) was obviously increased in the TNBS-3d group than the control group (
P
<
0.01). Similarly
the ICI in TNBS-7d group was significantly decreased (
P
<
0.01)
but MBP did not differ from the control group. The number of P2X3 positive neurons in DRG from the TNBS-3d and TNBS-7d groups was increased significantly compared to the control group (
P
<
0.01). Intrathecal injection of P2X3 inhibitor A-317491 significantly prolonged the interval of micturition (
P
<
0.01) in the TNBS-3d and TNBS-7d groups and reduced the maximum bladder pressure in TNBS-3d groups (
P
<
0.05).
Conclusion
2
P2X3 receptor in DRG plays an important role in the pathophysiological process of bladder overactivity induced by colitis
and inhibition of P2X3 receptor in DRG may be an effective treatment strategy for the overactive bladder.
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