Zhu L, Zhang W Y, Xu K X
Department of Urology, Peking University People's Hospital, Beijing 100044, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2022 Aug 18;54(4):735-740. doi: 10.19723/j.issn.1671-167X.2022.04.024.
To establish a model of bladder pain syndrome in SD rats by cyclophosphamide intraperitoneal injection, to evaluate the effectiveness of the model from the urodynamic and histological levels, to lay a zoological foundation for the clinical study of bladder pain syndrome, and to further guide clinical treatment.
Thirty-two 8-week-old SD rats were randomly divided into 4 groups, including acute test group, acute control group, chronic test group, and chronic control group, with 8 rats in each group. The acute test group received intraperitoneal injection of cyclophosphamide 150 mg/kg immediately after the measurement of urodynamic data on the first day, and urodynamic examination was performed again 2 days later. After that, the rats were sacrificed to obtain bladder tissue. In the chronic test group, after measuring the baseline data of urodynamics on the first day, cyclophosphamide 75 mg/kg was intraperitoneally injected on the first, fourth, and seventh days, and the rats were sacrificed after measuring the urodynamic data again on the eighth day to obtain bladder tissue. The acute control group and the chronic control group were injected with the same amount of normal saline during intraperitoneal injection, and the urodynamic testing time point were consistent with the corresponding test groups. Histopathological changes of the bladder were assessed by HE staining.
In each acute and chronic group, there were no intragroup differences in baseline urodynamic levels between the test and control groups. The urodynamic maximum bladder volume was significantly reduced in the acute test group after administration(=-2.961, < 0.05), histologically, severe interstitial edema, obvious inflammatory cell infiltration, mucosal edema and submucosal hemorrhage, and partial urothelium were absent could be seen, which were consistent with acute cystitis performance. The urodynamic maximum bladder capacity was significantly reduced in the chronic test group after administration (=-3.886, < 0.05), and the bladder compliance was lower than that in the control group, but not significant, the histological manifestations were urothelial exfoliation, interstitial edema, submucosal hemorrhage, infiltration of inflammatory cells such as lymphocytes, and dense vascular distribution.
In the acute test group, a single intraperitoneal injection of cyclophosphamide could induce acute bladder inflammation in the rats. In the chronic test group, repeated injections of cyclophosphamide could induce histological changes in chronic inflammation of chronic bladder pain syndrome in the rats. But the bladder function was not significantly impaired.
通过腹腔注射环磷酰胺建立SD大鼠膀胱疼痛综合征模型，从尿动力学和组织学水平评估模型的有效性，为膀胱疼痛综合征的临床研究奠定动物学基础，并进一步指导临床治疗。
将32只8周龄SD大鼠随机分为4组，包括急性试验组、急性对照组、慢性试验组和慢性对照组，每组8只。急性试验组在第一天测定尿动力学数据后立即腹腔注射环磷酰胺150mg/kg，2天后再次进行尿动力学检查。之后，处死大鼠获取膀胱组织。慢性试验组在第一天测定尿动力学基线数据后，于第一、四、七天腹腔注射环磷酰胺75mg/kg，第八天再次测定尿动力学数据后处死大鼠获取膀胱组织。急性对照组和慢性对照组在腹腔注射时注入等量生理盐水，尿动力学检测时间点与相应试验组一致。通过HE染色评估膀胱的组织病理学变化。
在各急性和慢性组中，试验组和对照组的基线尿动力学水平组内无差异。急性试验组给药后尿动力学最大膀胱容量显著降低（=-2.961，<0.05），组织学上可见严重的间质水肿、明显的炎性细胞浸润、黏膜水肿和黏膜下出血，部分尿路上皮缺失，符合急性膀胱炎表现。慢性试验组给药后尿动力学最大膀胱容量显著降低（=-3.886，<0.05），膀胱顺应性低于对照组，但差异不显著，组织学表现为尿路上皮脱落、间质水肿、黏膜下出血、淋巴细胞等炎性细胞浸润以及血管分布密集。
在急性试验组中，单次腹腔注射环磷酰胺可诱导大鼠急性膀胱炎症。在慢性试验组中，重复注射环磷酰胺可诱导大鼠慢性膀胱疼痛综合征慢性炎症的组织学变化。但膀胱功能未受到显著损害。
