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bFGF对大鼠急性脊髓损伤组织内质网应激(ERS)信号通路相关蛋白CHOP、Caspase12表达的影响

2021-07-07葛小刚蔡旗旗牟财国蔡杨阳

中国现代医生 2021年11期

葛小刚  蔡旗旗  牟财国  蔡杨阳

[摘要] 目的 探讨碱性成纤维细胞因子(bFGF)对大鼠急性脊髓损伤内质网应激(ERS)信号通路相关蛋白CHOP、Caspase12表达的影响。 方法 选取SD大鼠90只分为三组,每组各30只。Sham组为假手术组;SCI组采用HI-0400脊髓打击器制备急性脊髓损伤模型;bFGF组在SCI组基础上予bFGF蛛网膜下隙给药,评估损伤后不同时点后肢运动功能评分、脊髓细胞凋亡及脊髓组织CHOP、Caspase12表達情况。 结果 bFGF组损伤后21 d、28 d的BBB评分分别为(12.48±0.42)分、(13.53±0.47)分,均高于SCI组,差异有统计学意义(t=7.533、9.963,P<0.05)。bFGF组损伤后1 d、3 d、7 d细胞凋亡分别为(7.13±0.45)%、(12.42±1.21)%、(10.31±1.27)%,均低于SCI组,差异有统计学意义(t=4.684、8.945、6.507,P<0.05)。bFGF组CHOP及Caspase12表达分别为(7.66±0.74)分、(7.52±0.87)分,显著低于SCI组,差异有统计学意义(t=12.348、8.653,P<0.05)。 结论 bFGF可通过抑制ERS相关蛋白CHOP、Caspase12的表达,对大鼠急性脊髓损伤起保护作用。

[关键词] 碱性成纤维细胞因子;内质网应激;大鼠急性脊髓损伤;保护作用;脊髓损伤评分;白细胞介素1-β转换酶家族12

[中图分类号] R363          [文献标识码] A          [文章编号] 1673-9701(2021)11-0036-04

Effect of bFGF on the expression of proteins CHOP and Caspase12 related to endoplasmic reticulum stress(ERS) signaling pathway in acute spinal cord injury in rats

GE Xiaogang CAI Qiqi MOU Caiguo   CAI Yangyang

Department of Vascular Surgery, Taizhou First People′s Hospital in Zhejiang Province, Taizhou   318020, China

[Abstract] Objective To explore the effects of basic fibroblast growth factor(bFGF) on the expression of proteins CHOP and Caspase12 related to the endoplasmic reticulum stress(ERS) signaling pathway in acute spinal cord injury in rats. Methods A total of 90 SD rats were selected and divided into 3 groups, with 30 rats in each group. The sham group underwent the sham operation. The SCI group underwent the HI-0400 spinal cord percussion device to make acute spinal cord injury models. bFGF was administered to the subarachnoid space in the bFGF group on the basement of the SCI group. The hind legs motor function, spinal cord cell apoptosis and the expression of spinal cord tissue CHOP and Caspase12 at different times after injury were evaluated. Results The BBB scores of the bFGF group were (12.48±0.42) points and (13.53±0.47) points at 21 days and 28 days after injury, which were significantly higher than those in the SCI group, with statistical significance(t=7.533, 9.963; P<0.05). The cell apoptosis in the bFGF group at 1 day, 3 days, and 7 days after injury was (7.13±0.45)%, (12.42±1.21)%, (10.31±1.27)%, respectively, which were lower than those of the SCI group, the differences were statistically significant(t=4.684, 8.945, 6.507; P<0.05). The CHOP and Caspase12 expression in the bFGF group were (7.66±0.74) points and (7.52±0.87) points, respectively, which were significantly lower than those in the SCI group, with statistical significance(t=12.348, 8.653; P<0.05). Conclusion bFGF can protect rats from acute spinal cord injury by inhibiting the expression of ERS-related proteins CHOP and Caspase12.

[Key words] Basic fibroblast growth factor; Endoplasmic reticulum stress; Acute spinal cord injury in rats; Protective effect; Basso,Beattie & Bresnahan locomotor rating scale; Cystein-asparate protease 12

作为临床常见的中枢神经系统创伤,脊髓损伤发病率、致残率高,且随着近年来交通及建筑业的不断发展,其发病率逐年攀升。脊髓损伤主要病理机制为原发性损伤后的继发性损伤,其中脊髓神经元凋亡在脊髓继发损伤中有重要作用[1],且直接影响脊髓神经功能。最新研究结果显示,内质网应激(Endoplasmic reticulum stress,ERS)是细胞凋亡的又一途径,C/EBP同源性蛋白(C/EBP-homologous protein,CHOP)是其特异性转录因子[2]。作为新型神经营养因子,碱性成纤维细胞因子(Basic fibroblast growth factor,bFGF)能够调节神经细胞生长及分化,通过外源性bFGF给药能够对脊髓损伤修复起促进作用[3]。目前,关于bFGF对ERS介导的细胞凋亡研究较少,本研究选择大鼠90只构建急性脊髓损伤模型,旨在分析bFGF通过ERS信号通路对大鼠急性脊髓损伤的早期保护作用,现报道如下。

1 资料与方法

1.1 一般资料

90只健康SD雌性大鼠购自上海市公共卫生临床中心[生产许可SCXK(沪)2020-0002],体重210~240 g,平均(224±15)g;鼠龄6~9周,平均(7.31±0.33)周。……

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