Abstract:

Objective To evaluate the therapeutic effect of cyclosporin A (CsA) on hyaluronidase induced interstitial cystitis/bladder pain sydrome (IC/BPS) in rats. Methods Forty-five Sprague-Dawley rats were randomly divided into control group (15 rats, intravesical normal saline), model group(15 rats, intravesical hyaluronidase) and CsA-treated group (15 rats, intravesical hyaluronidase+CsA). Voiding patterms were investigated by cystometrography. The changes of pain in urogenital area were detected by Von-Frey Hairs. The NO level of bladder tissue were measured by using nitric acid deoxidize enzyme method. The mRNA 1evels of iNOS, IL-6, IL-10, IL-17 were analyzed with real time reverse transcription polymerase chain reaction. The IL-6, IL-10 and IL-17 level were measured by ELISA. Results Compared with control, the mRNA level of iNOS, IL-6, IL-10, IL-17 increased significantly (all P values<0.001). The CsA-treated group showed decreased mRNA levels of iNOS, IL-6, IL-10, IL-17 (all P values<0.05). In model group, the NO level was (9.73±2.62)μmol/g; the IL-6 level was (125.4±11.25) μg/g；the IL-10 level was（64.05±6.26)μg/g；the IL-17 level was（90.61±10.49)μg/g. The intercontraction intervals was(148.23±40.75)s; The bladder capacity was 0.41±0.06 m1. In control group, the NO level was 1.31±0.55 μmol/g; the IL-6 level was 55.18±5.07 μg/g. The IL-10 level was（32.12±3.82)μg/g; the IL-17 level was（44.45±4.92)μg/g. The intercontraction intervals was 441.90±34.96 s; The bladder capacity was 1.27±0.10 m1. Compared with control, the rats of model group showed high NO, IL-6, IL-10 and IL-17 level, decreased intercontraction intervals and bladder capacity, high pain score (all P<0.05). After administration of CsA, the NO, IL-6, IL-10 and IL-17 level of bladder reduced (P<0.001), which was 3.97±1.71 μmol/g, 62.29±6.68 μg/g, 33.51±5.77 μg/g and 51.88±6.67 μg/g, respectively. Both intercontraction intervals and bladder capacity increased significantly (both P<0.05). And they were 422.06±42.22 s and 1.14±0.15 ml, respectively. The pain score also decreased significantly (P<0.05). Conclusion In the IC/BPS rat model induced by hyaluronidase, intravesical CsA can significantly ameliorate the frequent urination and bladder pain, which may be related to the down-regulation of iNOS, NO, IL-6, IL-10 and IL-17.

Key words: Interstitial cystitis, Inflammation mediator, Bladder pain syndrome, Cyclosporin A

摘要：

目的 观察环孢素A（CsA）在透明质酸酶诱导的大鼠间质性膀胱炎/膀胱疼痛综合征（IC/BPS）中的治疗作用。方法 将45只成年雌性Sprague-Dawley（SD）大鼠（200～250 g），分为对照组15只（膀胱灌注生理盐水），模型组15只（膀胱灌注透明质酸酶），CsA治疗组15只（膀胱灌注透明质酸酶+CsA）。采用长期（1个月）间歇灌注透明质酸酶（4 g/L）构建大鼠IC/BPS模型，尿流动力学检测膀胱功能，VonFrey刷检测泌尿生殖区疼痛变化，硝酸还原酶法测定膀胱组织NO的含量，逆转录聚合酶链反应（RT-PCR）检测iNOS、IL-6、IL-10及IL-17 mRNA表达，ELISA法检测膀胱组织IL-6、IL-10及IL-17含量。结果 与对照组相比，模型组膀胱大鼠膀胱iNOS、IL-6、IL-10、IL-17 mRNA表达均显著升高（P<0.001），在予以CsA治疗后，其mRNA表达均显著下调（P<0.05）。模型组膀胱NO含量为9.73±2.62 μmol/g；IL-6含量为125.4±11.25 μg/g；IL-10含量为64.05±6.26 μg/g；IL-17含量为90.61±10.49 μg/g；排尿时间间隔为148.23±40.75 s；膀胱容量为0.41±0.06 mL。对照组膀胱NO含量为1.31±0.55 μmol/g；IL-6含量为55.18±5.07 μg/g；IL-10含量为32.12±3.82 μg/g；IL-17含量为44.45±4.92 μg/g；排尿时间间隔为441.90±34.96 s；膀胱容量为1.27±0.10 mL。与对照组比较，模型组大鼠膀胱NO、IL-6、IL-10、IL-17含量均明显升高，排尿时间间隔缩短，膀胱容量降低，疼痛评分显著增加（P<0.05）。与模型组相比，CsA治疗组大鼠的膀胱组织NO、IL-6、IL-10、IL-17含量均显著减少（P<0.001），分别为3.97±1.71 μmol/g；62.29±6.68 μg/g；33.51±5.77 μg/g；51.88±6.67 μg/g，排尿时间间隔及膀胱容量明显增加（P<0.05），分别为422.06±42.22 s、1.14±0.15 mL，疼痛评分也明显下调（P<0.05）。结论 在透明质酸酶诱导的IC/BPS大鼠模型中，CsA膀胱灌注治疗能显著改善大鼠的尿流动力学及疼痛症状，这可能与其下调iNOS、NO、IL-6、IL-10及IL-17等炎症介质的表达有关。

关键词: 膀胱疼痛综合征, 炎症介质, 环孢素 A, 间质性膀胱炎