目的:为了研究鞘内注射CCPA的效果,腺苷A1受体激动剂,环磷酰胺(CYP)致膀胱炎大鼠排尿功能的研究.
方法:将30只8周龄SD大鼠随机分为对照组(n=15)和膀胱炎组(n=15)。通过单次腹腔注射CYP(200mg/kg,溶解在生理盐水中)。对照组大鼠腹腔注射生理盐水。PE10导管通过L3-4椎间隙到达L6-S1脊髓水平,鞘内注射。腹腔注射后48小时,进行尿动力学测试,以观察鞘内给药10%二甲基亚砜(载体)和1nmolCCPA对排尿参数的影响,包括基础压(BP),阈值压力(TP),最大排尿压力(MVP),收缩间期(ICI),作废卷(VV),剩余体积(RV),膀胱容量(BC),和排尿效率(VE)。通过苏木精-伊红染色(HE染色)研究膀胱炎大鼠膀胱的组织学变化。此外,采用Westernblot和免疫荧光法研究两组大鼠脊髓背侧L6-S1中腺苷A1受体的表达。
结果:HE染色显示粘膜下出血,水肿,膀胱炎大鼠膀胱壁炎性细胞浸润。尿动力学试验显示血压显著升高,TP,膀胱炎大鼠的MVP和RV,而ICI,VV,BC和VE显著下降,表明膀胱过度活动。CCPA抑制对照组和膀胱炎大鼠的排尿反射,TP显著增加,ICI,VV,BC,和VE,但对血压没有显著影响,MVP和RV。Westernblot和免疫荧光显示,对照组和膀胱炎大鼠L6-S1脊髓背侧腺苷A1受体的表达无明显差异。
结论:本研究结果表明鞘内注射腺苷A1受体激动剂CCPA可缓解CYP诱导的膀胱过度活动。此外,我们的研究结果表明,腰骶脊髓的腺苷A1受体可能是治疗膀胱过度活动症的一个有希望的靶点.
OBJECTIVE: To investigate the effect of intrathecal administration of CCPA, an adenosine A1 receptor agonist, on voiding function in rats with cystitis induced by cyclophosphamide (CYP).
METHODS: Thirty 8-week-old Sprague Dawley rats were randomly divided into a control group (n = 15) and a cystitis group (n = 15). Cystitis was induced by a single intraperitoneal injection of CYP (200 mg/kg, dissolved in physiological saline) in rats. Control rats were injected intraperitoneally with physiological saline. The PE10 catheter reached the level of L6-S1 spinal cord through L3-4 intervertebral space for intrathecal injection. Forty-eight hours after intraperitoneal injection, urodynamic tests were conducted to observe the effect of intrathecal administration of 10% dimethylsulfoxide (vehicle) and 1 nmol CCPA on micturition parameters, including basal pressure (BP), threshold pressure (TP), maximal voiding pressure (MVP), intercontraction interval (ICI), voided volume (VV), residual volume (RV), bladder capacity (BC), and voiding efficiency (VE). Histological changes of the bladder of cystitis rats were studied through hematoxylin-eosin staining (HE staining). Moreover, Western blot and immunofluorescence were used to study the expression of adenosine A1 receptor in the L6-S1 dorsal spinal cord in both groups of rats.
RESULTS: HE staining revealed submucosal hemorrhage, edema, and inflammatory cell infiltration in the bladder wall of cystitis rats. The urodynamic test showed significant increase in BP, TP, MVP and RV in cystitis rats, while ICI, VV, BC and VE decreased significantly, indicating bladder overactivity. CCPA inhibited the micturition reflex in both control and cystitis rats, and significantly increased TP, ICI, VV, BC, and VE, but had no significant effect on BP, MVP and RV. Western blot and immunofluorescence showed that there was no significant difference in the expression of adenosine A1 receptor in the L6-S1 dorsal spinal cord between the control and cystitis rats.
CONCLUSIONS: The findings of this study suggest that intrathecal administration of the adenosine A1 receptor agonist CCPA alleviates CYP-induced bladder overactivity. Furthermore, our results indicate that the adenosine A1 receptor in the lumbosacral spinal cord may be a promising target for treatment of bladder overactivity.