Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
J Inflamm (Lond). 2010 Apr 19;7:17. doi: 10.1186/1476-9255-7-17.
Urinary bladder and renal dysfunction are secondary events associated with spinal cord injury (SCI) in humans. These secondary events not only compromise quality of life but also delay overall recovery from SCI pathophysiology. Furthermore, in experimental models the effects of SCI therapy on bladder and renal functions are generally not evaluated. In this study, we tested whether simvastatin improves bladder and renal functions in a rat model of experimental SCI.
SCI was induced by controlled contusion of T9-T10 in adult female rats. Simvastatin (5 mg/Kg body weight) was administered at two hours after SCI and repeated every 24 hours until the end point. Simvastatin-treated SCI animals (simvastatin group) were compared with vehicle-treated SCI animals (vehicle group) in terms of the Basso Beattie Bresnahan score, tissue morphology, cell death, and bladder/renal functions.
The urinary bladder of vehicle animals showed a 4.3-fold increase in size and a 9-fold increase in wet weight compared to sham animals. Following SCI, the urine to plasma osmolality ratio increased initially but decreased 1 week after SCI. Hematoxylin and eosin staining of bladder tissue showed transitional epithelial hyperplasia, degeneration of lamina propria, and enlargement of tunica adventia in addition to detrusor muscle hypertrophy. Rats treated with simvastatin for 14 days displayed remarkable recovery by showing decreased bladder size and maintenance of a normal urine/plasma osmolality ratio, in addition to improved locomotion. The muscularis layer of the bladder also regained its compact nature in simvastatin animals. Moreover, SCI-induced renal caspase-3 activity was significantly decreased in the simvastatin group indicating the ability of simvastatin to reduce the renal tubular apoptosis.
Post-injury administration of simvastatin ameliorates bladder and renal dysfunction associated with SCI in rats.
在人类中，脊髓损伤（SCI）会引起膀胱和肾功能障碍，这些继发事件不仅降低了生活质量，还延迟了 SCI 病理生理学的整体恢复。此外，在实验模型中，通常不会评估 SCI 治疗对膀胱和肾功能的影响。在这项研究中，我们测试了辛伐他汀是否可以改善实验性 SCI 大鼠模型中的膀胱和肾功能。
通过在成年雌性大鼠的 T9-T10 处进行受控挫伤来诱导 SCI。在 SCI 后两小时给予辛伐他汀（5mg/Kg 体重），并在 24 小时后重复给药，直至达到终点。将辛伐他汀治疗的 SCI 动物（辛伐他汀组）与载体治疗的 SCI 动物（载体组）在 Basso Beattie Bresnahan 评分、组织形态、细胞死亡以及膀胱/肾功能方面进行比较。
与假手术动物相比，载体动物的膀胱体积增加了 4.3 倍，湿重增加了 9 倍。在 SCI 后，尿与血浆渗透压比值最初增加，但在 SCI 后 1 周下降。膀胱组织的苏木精和伊红染色显示，除逼尿肌肥大外，移行上皮过度增生、固有层变性和外膜增厚。用辛伐他汀治疗 14 天的大鼠显示出明显的恢复，表现为膀胱体积减小，尿/血浆渗透压比值正常，运动功能改善。辛伐他汀组的膀胱肌层也恢复了正常的致密性。此外，SCI 诱导的肾半胱氨酸天冬氨酸蛋白酶-3 活性在辛伐他汀组显著降低，表明辛伐他汀能够减少肾小管凋亡。
伤后给予辛伐他汀可改善大鼠 SCI 相关的膀胱和肾功能障碍。
