| 吡拉西坦通过MAPK通路治疗大鼠脊髓损伤的疗效观察与机制研究 |
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投稿时间：2023-05-18 修订日期：2024-02-26
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| 期刊信息：《中国骨伤》年，第卷，第期，第-页 |
| DOI： |
| 基金项目:陕西省重点研发计划项目“两链”融合重点专项（2021LLRH-08）；陕西省教育厅青年创新团队计划（22JP018）；秦都区2022年科技计划项目（QK2022sf04） |
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| 中文摘要:[摘要]：目的：观察吡拉西坦通过MAPK通路治疗脊髓损伤大鼠的作用机制及治疗效果。方法：将54只6周龄（体重为80 - 100g）SD雌性健康大鼠使用随机数字表法分为三组，分别为假手术组、脊髓损伤组、吡拉西坦组各18只。脊髓损伤组、吡拉西坦组使用打击器建立脊髓损伤模型，假手术组不损伤脊髓。吡拉西坦组按照5 ml/kg标准尾静脉注射吡拉西坦注射液，连续干预3天，每日1次。其他组注射等剂量、等次数、等时长的生理盐水。在术后1d、3d、7d处死取材。观察项目包括术后1天、3天和7天的大鼠脊髓损伤行为学评分（Basso, Beattie and Bresnahan locomotor rating scale，BBB）、脊髓炎症因子白细胞介素-6（interleukin-6, IL-6）、白细胞介素-10（interleukin-10, IL-10）、白细胞介素-1β（interleukin-1β, IL-1β）、肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）水平变化、HE染色、水通道蛋白-4（aquaporin 4,AQP4）的免疫组织化学染色和MAPK信号通路的变化，以反映损伤后的炎症反应、细胞结构改变和信号通路活性。结果：与脊髓损伤组比，吡拉西坦组HE染色脊髓出血及坏死区域面积减小，免疫组化显示AQP4染色变淡。吡拉西坦组的BBB评分在7天后提升至9±2分，与脊髓损伤组相比，差异具有统计学意义（P < 0.05）。吡拉西坦组的IL-6，IL-10，IL-1β和TNF-α水平在7天后被抑制至34.08±0.72 pg/ml, 30.11±1.74 pg/ml, 32.47±2.09 pg/ml和20.52±0.49 pg/ml，与脊髓损伤组相比，差异具有统计学意义（P < 0.05）。在吡拉西坦组中，p-ERK、p-JNK和p-p38的表达水平在7天后显著降至0.27±0.02、0.49±0.04和0.25±0.02。与脊髓损伤组相比，差异具有统计学意义（p < 0.05）。结论：吡拉西坦干预后能够提高脊髓损伤大鼠的运动功能，降低脊髓炎症反应及AQP4的表达，抑制MAPK信号通路活性。 |
| 【关键词】关键词：吡拉西坦 脊髓损伤 MAPK信号通路 |
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| Mechanism of Piracetam treating spinal cord injury in rats through MAPK pathway |
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| ABSTRACT [Abstract]:Objective: To observe the mechanism and therapeutic effect of piracetam on spinal cord injury in rats via the MAPK pathway.Methods: Fifty-four 6-week-old (weighing 80-100g) SD female healthy rats were divided into three groups by the random number table method: sham operation group, spinal cord injury group, and piracetam group, with 18 rats in each. The spinal cord injury and piracetam groups were subjected to spinal cord injury using a hitter. The sham operation group was not injured. The piracetam group received piracetam injection via the tail vein at a dosage of 5 ml/kg, continuously for 3 days, once daily. The other groups received an equivalent volume, frequency, and duration of saline injections. Samples were collected on post-operative days 1, 3, and 7. Observation items included the Basso, Beattie, and Bresnahan locomotor rating scale (BBB) scores on post-operative days 1, 3, and 7; the levels of inflammatory cytokines including interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α); changes in HE staining, immunohistochemical staining of aquaporin 4 (AQP4), and the MAPK signaling pathway. This reflected post-injury inflammatory responses, cellular structural changes, and signaling pathway activity.Results: Compared with the spinal cord injury group, the piracetam group showed reduced areas of spinal cord hemorrhage and necrosis in HE staining, and immunohistochemistry showed lighter AQP4 staining.The BBB score of the piracetam group increased to 9±2 points after 7 days, showing a statistically significant difference when compared with the spinal cord injury group (P < 0.05). The levels of IL-6, IL-10, IL-1β, and TNF-α in the piracetam group were suppressed to 34.08±0.72 pg/ml, 30.11±1.74 pg/ml, 32.47±2.09 pg/ml, and 20.52±0.49 pg/ml on day 7, showing statistically significant differences when compared with the spinal cord injury group (P < 0.05). In the piracetam group, the expression levels of p-ERK, p-JNK, and p-p38 significantly decreased to 0.27±0.02, 0.49±0.04, and 0.25±0.02 on day 7, respectively. The differences were statistically significant compared to the spinal cord injury group (p < 0.05).Conclusion: Piracetam intervention can improve motor function in rats with spinal cord injuries, reduce spinal cord inflammation and AQP4 expression, and inhibit the activity of the MAPK signaling pathway. |
| KEY WORDS Keywords: piracetam spinal cord injury MAPK signaling pathway |
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