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目的神经病理性疼痛在临床中很常见,但治疗效果欠佳。文中应用鞘内移植神经干细胞(neural stem cells,NSC)治疗坐骨神经慢性缩窄性损伤模型(chronic constriction injury,CCI)大鼠,并观察脊髓背角和背根神经节(dorsal root gan-glion,DRG)胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)表达的变化。方法成年SD大鼠72只,随机均分为A组(假手术+细胞培养液)、B组(CCI+细胞培养液)和C组(CCI+NSC),然后各组再随机分为:A1、B1和C1组(CCI后3 d鞘内移植组)和A2、B2和C2组(CCI后10 d鞘内移植组),每组12只。分别于术前1 d和术后1、3、7、14、21 d测机械痛阈(mechanical withdrawal threshold,MWT)和热痛阈(thermal withdrawal latency,TWL)。术后7 d、14 d和21 d采用免疫组织化学染色和Real-time PCR技术观察DRG、脊髓背角中GDNF的表达变化。结果①与A组相比,B1、B2、C1、C2组术前1 d、术后1 d和21d MWT和TWL差异无统计学意义(P>0.05);术后3d MWT和TWL逐渐降低,至术后7d降低至最低点,在此期间各时间点痛阈与A1组比较,B1、B2、C1、C2组数值均有显著降低(P<0.01),之后缓慢升高,于术后21 d恢复至术前水平;与B组比较,C组术后7d、14dMWT和TWL明显上升(P<0.01)。②与B组比较,A组术后7d、14d和21d各组大鼠GDNF的表达呈低水平(P<0.05);术后7 d,C1组GDNF的表达量较B1组明显升高(P<0.05);术后14 d和21 d,C1、C2组GDNF的表达量高于B1、B2组(P<0.05)。结论鞘内移植NSC可通过提高脊髓背角和DRG中的GDNF表达量,从而对CCI模型引起的神经病理性疼痛起预防和治疗作用。
Purpose Neuropathic pain is clinically common, but its efficacy is poor. In the present study, intrathecal neural stem cells (NSCs) were used to treat chronic constriction injury (CCI) rats, and dorsal root gan-glion (DRG) ) Glial cell line-derived neurotrophic factor (GDNF) expression changes. Methods Seventy-two adult SD rats were randomly divided into three groups: sham operation group (sham operation + cell culture), group B (CCI + cell culture) and group C (CCI + NSC) Groups B1 and C1 (intrathecal transplantation 3 days after CCI) and groups A2, B2 and C2 (intrathecal transplantation 10 days after CCI), 12 in each group. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1 day and 1, 3, 7, 14 and 21 days after operation. At 7 d, 14 d and 21 d after operation, the expression of GDNF in DRG and spinal dorsal horn was observed by immunohistochemistry and Real-time PCR. Results ① Compared with group A, there was no significant difference in MWT and TWL between preoperative 1 d, postoperative 1 d and 21 d in B1, B2, C1 and C2 groups (P> 0.05) The pain threshold at each time point was significantly lower than that in A1 group (P <0.01), and then slowly increased at 21 days after operation d to the preoperative level. Compared with group B, the MWT and TWL of group C at 7d and 14d after operation increased significantly (P <0.01). ② Compared with group B, the expression of GDNF in group A was lower at 7d, 14d and 21d after operation (P <0.05). On the 7th day after operation, the expression of GDNF in group C1 was significantly higher than that of group B1 <0.05). The expression of GDNF in C1 and C2 groups was higher than that in B1 and B2 groups on the 14th day and the 21st day after operation (P <0.05). Conclusion Intrathecal transplantation of NSC can prevent and treat neuropathic pain induced by CCI model by increasing GDNF expression in spinal dorsal horn and DRG.