The effects of Glivec on the urinary bladder excitation of rats with suprasacral or sacral spinal cord transection

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• 作者：Jianping Deng ; Yongge Zhang ; Liang Wang ; Jiang Zhao ; Bo Song ; Longkun Li
• 关键词：Bladder ; Interstitial cell ; Suprasacral cord injury ; Sacral cord injury ; Glivec
• 刊名：Journal of Surgical Research
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：183
• 期：2
• 页码：598-605
• 全文大小：1922 K

文摘

Background

To investigate the effects of the c-kit blocker imatinib mesylate (Glivec) on the bladders of animals with suprasacral cord injury (SSCI) and sacral cord injury (SCI).

Materials and methods

We randomized 60 female Sprague-Dawley rats into control, sham, SSCI (T8/9 transection), and SCI (S1-3 transection) groups. Six weeks later, we evaluated the effects of stepwise Glivec administrations on urinary bladder contraction using cystometry and the detrusor strip stretch-test. We investigated spontaneous calcium transients of kit-positive interstitial cells of Cajal (ICCs) with the preloaded Ca²⁺ indicator fluo-3AM. The expression levels of c-kit and the number of ICCs in those bladders were determined using Western blot and fluorescence staining analyses, respectively.

Results

Bladder capacity and compliance were decreased in SSCI bladders and increased in SCI bladders (P < 0.05). The amplitude and frequency of spontaneous contractions of detrusor strips, the frequency and relative fluorescence intensity of the spontaneous Ca²⁺ waves, and c-kit expression in the bladder were significantly increased in the SSCI group and decreased in the SCI group compared with the control and sham groups (P < 0.05). The dose-dependent effects of Glivec also confirmed consistent functional variations in bladder activity.

Conclusions

The expressions and effects of Glivec were enhanced in SSCI bladders and inhibited in SCI bladders, which may indicate potential roles of ICCs for the c-kit signaling pathway in the pathogenesis of SSCI and SCI bladder.