CAJ | 학술논문

目的观察突触后致密物质-95(PSD-95)多肽疫苗对大鼠神经病理性痛的影响.方法成年雌性SD大鼠,制备保留性神经损伤(SNI)模型,7d后选取SNI模型成功的大鼠24只,随机分为4组(n=6):NP组、磷酸盐缓冲液(PBS)组、匙孔虫戚血蓝蛋白(KLH)组及PSD-95组.PSD-95组沿背部两侧皮下多点注射PSD-95多肽疫苗3次,每隔2周注射1次；PBS、KLH组分别给予PBS和KLH.分别于制备SNI前1 d(基础值)、第1次免疫前1d及第3次免疫后7d和14 d(T0-3)时测定机械痛阈；于T3时处死大鼠,取脊髓腰膨大组织,采用逆转录-聚合酶链反应(RT-PCR)法测定脑源性神经营养因子(BDNF) mRNA表达.结果与T0时比较,T1时各组机械痛阈均降低(13.2±1.1比1.9±0.5:12.9±0.9比1.9 ±0.7;13.5±1.0比1.8±0.5;13.1±1.1比1.7±0.6)；T2、T3时NP、PBS和KLH组机械痛阈降低(2.4±0.6、2.5±0.6；3.2±0.9、3.4±0.8;3.3±0.8、3.5±1.1)(P＜0.05).与T1时比较,PSD-95组T2、T3时机械痛阈升高(1.7±0.6比10.5 ±2.1、11.2±1.9),BDNF mRNA表达下调(1.48±0.21比0.92±0.13、0.88 ±0.12)(P＜0.05)；PBS组和KLH组其余时点各指标差异无统计学意义(P＞0.05).与NP组比较,T2、T3时PSD-95组机械痛阈升高(2.4±0.6比10.5±2.1;2.5±0.6比11.2±1.9),BDNF mRNA表达下调(1.48±0.17比0.92 ±0.13;1.52±0.23比0.88±0.12)(P ＜0.05);PBS组和KLH组各指标差异无统计学意义(P＞0.05).结论 PSD-95多肽疫苗对神经病理性痛大鼠具有镇痛作用,其机制可能与下调脊髓BDNF mRNA的表达有关.
목적 관찰돌촉후치밀물질-95(PSD-95)다태역묘대대서신경병이성통적영향.방법 성년자성SD대서,제비보류성신경손상(SNI)모형,7d후선취SNI모형성공적대서24지,수궤분위4조(n=6):NP조、린산염완충액(PBS)조、시공충척혈람단백(KLH)조급PSD-95조.PSD-95조연배부량측피하다점주사PSD-95다태역묘3차,매격2주주사1차；PBS、KLH조분별급여PBS화KLH.분별우제비SNI전1 d(기출치)、제1차면역전1d급제3차면역후7d화14 d(T0-3)시측정궤계통역；우T3시처사대서,취척수요팽대조직,채용역전록-취합매련반응(RT-PCR)법측정뇌원성신경영양인자(BDNF) mRNA표체.결과 여T0시비교,T1시각조궤계통역균강저(13.2±1.1비1.9±0.5:12.9±0.9비1.9 ±0.7;13.5±1.0비1.8±0.5;13.1±1.1비1.7±0.6)；T2、T3시NP、PBS화KLH조궤계통역강저(2.4±0.6、2.5±0.6；3.2±0.9、3.4±0.8;3.3±0.8、3.5±1.1)(P＜0.05).여T1시비교,PSD-95조T2、T3시궤계통역승고(1.7±0.6비10.5 ±2.1、11.2±1.9),BDNF mRNA표체하조(1.48±0.21비0.92±0.13、0.88 ±0.12)(P＜0.05)；PBS조화KLH조기여시점각지표차이무통계학의의(P＞0.05).여NP조비교,T2、T3시PSD-95조궤계통역승고(2.4±0.6비10.5±2.1;2.5±0.6비11.2±1.9),BDNF mRNA표체하조(1.48±0.17비0.92 ±0.13;1.52±0.23비0.88±0.12)(P ＜0.05);PBS조화KLH조각지표차이무통계학의의(P＞0.05).결론 PSD-95다태역묘대신경병이성통대서구유진통작용,기궤제가능여하조척수BDNF mRNA적표체유관.
Objective To investigate the effect of postsynaptic density (PSD)-95 peptide vaccine on neuropathic pain (NP) in rats.Methods Adult female SD rats were selected to produce retained nerve injury (SNI) model.Seven days after successful SNI surgery,24 rats were randomly divided into 4 groups (n =6)..NP group,PBS group,keyhole limpet hemocyanin (KLH) group and PSD-95 group.Rats in PSD-95 group were given multi-point injection of PSD-95 peptide vaccine on the back subcutaneously,on both sides 3 times at 2 weeks interval,and those in PBS and KLH groups were given PBS or KLH.The mechanical pain threshold was determined one day before the preparation of SNI (underlying value),1 day before the first immunization,7 days and 14 days after the third immunization (T0-3).Rats were killed at T3 to determine the mRNA expression of brain-derived neurotrophic factor (BDNF) in the spinal cord lumbar enlargement.Results Compared with T0,the mechanical pain threshold of each group at T1 was decreased (13.2±1.1 vs.1.9±0.5; 12.9±0.9 vs.1.9±0.7; 13.5±1.0vs.1.8±0.5; 13.1±1.1 vs.1.7 ± 0.6),and that in NP group,PBS group and KLH group at T2 and T3 was decreased (2.4 ± 0.6,2.5 ± 0.6 ; 3.2 ± 0.9,3.4 ± 0.8 ; 3.3 ± 0.8,3.5 ± 1.1) (P ＜ 0.05).Compared with T1,the mechanical pain threshold in PSD-95 group at T2 and T3 was increased (1.7 ±0.6 vs.10.5 ±2.1,11.2 ± 1.9),and the mRNA expression of BDNF was down-regulated (1.48 ± 0.21 vs.0.92 ± 0.13,0.88 ± 0.12) (P ＜ 0.05).As compared with NP group,the mechanical pain threshold in PSD-95 group was increased (2.4 ±0.6 vs.10.5 ±2.1 ; 2.5 ±0.6 vs.11.2 ± 1.9),and the mRNA expression of BDNF was downregulated (1.48±0.17 vs.0.92±0.13; 1.52±0.23 vs.0.88±0.12) (P＜0.05).There was no significant difference in various indicators between PBS group and KLH group (P ＞ 0.05).Conclusion PSD-95 peptide vaccine has analgesic effects on neuropathic pain in rats,which may be related to the downregulation of the mRNA expression of spinal BDNF.