尼莫地平对脊髓损伤大鼠脊髓组织Ca^(2+)及细胞焦亡的影响

Effects of Nimodipine on calcium ion and pyroptosis of spinal cord tissue in rats with spinal cord injury

目的研究尼莫地平(Nimodipine)对脊髓损伤(SCI)大鼠及脊髓组织Ca^(2+)及细胞焦亡的影响。方法将36只SD雄性大鼠按照随机数表法分为假手术组(Sham组)、脊髓损伤组(SCI组)和SCI+Ca^(2+)抑制剂尼莫地平组(Nimodipine组)各12只。脊髓撞击法制备大鼠SCI模型,BBB评分评估大鼠运动功能,荧光探针检测脊髓组织Ca^(2+)含量,酶联免疫吸附法检测白介素1β(IL-1β)及白介素18(IL-18)含量,蛋白免疫印迹检测细胞焦亡相关蛋白NOD样受体蛋白3(NLRP3)及半胱氨酸/天冬氨酸蛋白酶1(Caspase-1)的表达水平。结果与Sham组比较,SCI组大鼠BBB评分降低,差异有统计学意义(P<0.05);与Sham组比较,SCI组大鼠Ca^(2+)(18.92±3.60)、IL-1β[(383.66±45.42)pg/mL]、IL-18[(364.21±38.23)pg/mL]含量和NLRP3(0.93±0.19)、Caspase-1(0.98±0.08)的表达水平明显增加,差异均有统计学意义(P<0.05);与SCI组比较,Nimodipine组大鼠1 d、3 d、7 d的BBB评分稍增高,但差异均无统计学意义(P>0.05),而14 d、21 d及28 d大鼠BBB评分明显增高,差异均有统计学意义(P<0.05);与SCI组比较,Nimodipine组大鼠Ca^(2+)(11.73±4.31)、IL-1β[(292.93±28.48)pg/mL]、IL-18[(279.81±22.52)pg/mL]含量和NLRP3(0.79±0.18)及Caspase-1(0.63±0.10)的表达水平明显减少,差异均有统计学意义(P<0.05)。结论尼莫地平可能通过抑制Ca^(2+)来改善SCI大鼠的细胞焦亡及运动功能。

Objective To study the effects of Nimodipine on calcium ion and pyroptosis of spinal cord tissue in rats with spinal cord injury(SCI).Methods Thirty-six male SD rats were divided into three groups by random number table method:sham group,spinal cord injury(SCI group),SCI+Ca^(2+)inhibitor Nimodipine group(Nimodipine group),with 12 rats in each group.The spinal cord impingement method was used to prepare the SCI model,and the sports function was observed with BBB test.Ca^(2+)content was detected with fluorescence probe,and IL-1βand IL-18 content were detected with enzyme linked immunosorbent assay.The expression of pyroptosis-related NLRP3 and Caspase-1 in spinal was detected by Western blot.Results Compared with the Sham group,the BBB score of the rats was decreased in SCI group(P<0.05).Compared with the Sham group,the content of Ca^(2+)(18.92±3.60),IL-1β[(383.66±45.42)pg/mL],IL-18[(364.21±38.23)pg/mL],and the expression of NLRP3(0.93±0.19),and Caspase-1(0.98±0.08)were increased in SCI group,with statistically significant differences(all P<0.05).Compared with the SCI group,the BBB score of rats increased slightly at 1 d,3 d and 7 d in Nimodipine group(P>0.05),and the BBB score of the rats was increased significantly at 14 d,21 d,and 28 d(all P<0.05).Compared with the SCI group,the content of Ca^(2+)(11.73±4.31),IL-1β[(292.93±28.48)pg/mL],and IL-18[(279.81±22.52)pg/mL],and the expression of NLRP3(0.79±0.18)and Caspase-1(0.63±0.10)were decreased significantly in Nimodipine group(all P<0.05).Conclusion Nimodipine may improve the pyroptosis and motor function of SCI rats by inhibiting Ca^(2+).