维格列汀对大鼠脊髓损伤后神经细胞凋亡及运动功能恢复的影响

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摘要目的：探究维格列汀（Vilda）对大鼠脊髓损伤（SCI）后神经细胞凋亡及运动功能恢复的影响。方法：雌性SD大鼠随机分成3组（n=16）：Sham组、SCI组、SCI+Vilda组；采用血管夹压迫法建立大鼠SCI模型，成模后SCI+Vilda组按10 mg·kg-1·d-1的剂量灌胃给药，SCI组大鼠给予等量0.9%氯化钠溶液；在术后第1、第3、第7、第14、第21、第28天进行后肢运动功能恢复情况评估（BBB评分）；术后第3天提取脊髓组织进行组织免疫荧光染色检测Cleaved Caspase 3，提取组织蛋白进行Western blot检测Bcl-2、Bax、Cleaved Caspase 3蛋白的表达情况；术后第7天提取脊髓组织进行尼氏染色检测存活神经元；术后第28天，对各组大鼠进行足印迹步态分析。结果：与Sham组比较，SCI组BBB评分显著降低，步态不一致，脊髓前角运动神经元数量减少，免疫荧光显示Cleaved Caspase 3表达增强，Western blot显示Bax、Cleaved Caspase 3表达上升，Bcl-2表达下降（P＜0.05）；与SCI组比较，SCI+Vilda组BBB评分明显提升，步态一致性更好，脊髓前角运动神经元数量增加，Cleaved Caspase 3荧光表达减弱，Bax、Cleaved Caspase 3表达下降，Bcl-2表达上升（P＜0.05）。结论：Vilda可抑制SCI大鼠脊髓神经细胞的凋亡，从而促进大鼠SCI后运动功能的恢复。

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	徐天臻
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	汤呈宣

关键词 ：脊髓损伤, 维格列汀, 凋亡, 运动功能恢复, 大鼠

Abstract：Objective: To investigate the effect of Vildagliptin (Vilda) on locomotor function recovery and neural cell apotosis in a rat model of spinal cord injury. Methods: Forty-eight SD rats were randomly divided into 3 groups (n=16): the Sham group, the SCI group and the SCI+Vilad group. Clip compression SCI model was established as previously described. The SCI+Vilad group was treated with Vilad at a dose of 10 mg·kg-1·d-1 by gavage for 7 days in a row, then once every 3 days; the SCI group was treated with the same dosage of normal saline. The Basso-Beattie-Bresnahan (BBB) score was obtained at 1, 3, 7, 14, 21, 28 d after operation. Immunofluorescence staining and Western blot were used to detect the expression of apoptotic related proteins expression (Bcl-2, Bax, Cleaved Caspase 3) at 3 d after operation. Nissl staining was performed at 7 d after operation to detect the surviving neurons. At 28 d, the, the footprint analysis was used to assess the locomotor recovery. Results: Compared with the Sham group, SCI group showed significantly lower BBB scores and inconsistent footprints; the number of VMNs was decreased significantly. Immunofluorescence staining and western blot results showed enhanced expression of apoptotic related proteins (Bax, Cleaved Caspase 3), but the expression of anti-apoptotic related protein (Bcl-2) was decreased (P<0.05). Compared with the SCI group, the rats in SCI+Vilda group got higher BBB scores, more consistent footprints; the number of VMNs was also increased. At the same time, the expression of apoptotic related proteins (Bax, Cleaved Caspase 3) was decreased significantly and the expression of anti-apoptotic related protein (Bcl-2) was increased obviously (P<0.05). Conclusion: All of these findings indicated that Vildagliptin shows neuroprotective effect after SCI in rats via inhibiting the VMNs apoptosis, and finally promotes the locomotor recovery.

Key words： spinal cord injury vildagliptin apoptosis locomotor revovery rats

收稿日期: 2018-12-10

通讯作者: 汤呈宣，主任医师，教授，硕士生导师，Email：tangchengxuan@wmu.edu.cn。

作者简介: 徐天臻（1992-），男，浙江诸暨人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2019/V49/I7/523

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