目的 探讨多克隆神经细胞粘附分子抗体(P-NCAM-Ab)对A型肉毒毒素(BTX-A)生物学效应的影响.方法 选取雄性SD大鼠90只,按随机数字表法将其分为正常对照组、BTX-A组、P-NCAM-Ab组,每组30只.给予BTX-A组和P-NCAM-Ab组大鼠右侧腓肠肌BTX-A 0.5 U(100μl)注射,正常对照组大鼠则注射同等体积的生理盐水,第3天时在P-NCAM-Ab组大鼠右侧腓肠肌同一位点注射P-NCAM-Ab 20 U.注射前、后,动态测量大鼠腓肠肌肌肉的收缩强度及湿重变化,并通过乙酰胆碱酯酶染色和氯化金染色观察大鼠运动终板及可视神经纤维的变化情况.结果 干预后,正常对照组大鼠腓肠肌肌肉的收缩强度随时间延长而逐渐增加,BTX-A组和P-NCAM-Ab组则呈现出先下降后上升的趋势.与正常对照组同时间点比较,BTX-A组和P-NCAM-Ab组大鼠注射BTX-A后3d及1,2,4,6,8,10周时的腓肠肌肌肉收缩强度均较弱(P＜0.05);与BTX-A组同时间点比较,除注射后3d及1周,P-NCAM-Ab组大鼠剩余时间点腓肠肌肌肉的收缩强度均较BTX-A组弱(P＜0.05).BTX-A组和P-NCAM-Ab组大鼠腓肠肌收缩强度的恢复时间长于正常对照组(P＜0.05),且P-NCAM-Ab组的恢复时间长于BTX-A组(P＜0.05).BTX-A组和P-NCAM-Ab组大鼠腓肠肌湿重百分比随时间增长呈现出先下降后上升的趋势,且注射后3d及1,2,4周,BTX-A组和P-NCAM-Ab组组间比较,差异有统计学意义(P＜0.05).注射BTX-A后1,2,4,8,12周,BTX-A组及P-NCAM-Ab组运动终板染色均逐渐加深,但P-NCAM-Ab组大鼠运动终板同时间点内染色均浅于BTX-A组.BTX-A组和P-NCAM-Ab组大鼠运动终板阳性反应区域平均光密度值随时间延长而逐渐增加,且P-NCAM-Ab组在第1,2,4,8,12周时的平均光密度值低于BTX-A组(P＜0.05).BTX-A组和P-NCAM-Ab组大鼠神经纤维数量的变化趋势相似,除注射后3d、12周,2组剩余时间点神经纤维数量与正常对照组比较,差异有统计学意义(P＜0.05),且2组剩余时间点神经纤维数量间比较,差异亦有统计学意义(P＜0.05).结论 给予大鼠腓肠肌P-NCAM-Ab局部注射后,可增强BTX-A的生物学效应,并延长其单次注射后的疗效持续时间.
目的 探討多剋隆神經細胞粘附分子抗體(P-NCAM-Ab)對A型肉毒毒素(BTX-A)生物學效應的影響.方法 選取雄性SD大鼠90隻,按隨機數字錶法將其分為正常對照組、BTX-A組、P-NCAM-Ab組,每組30隻.給予BTX-A組和P-NCAM-Ab組大鼠右側腓腸肌BTX-A 0.5 U(100μl)註射,正常對照組大鼠則註射同等體積的生理鹽水,第3天時在P-NCAM-Ab組大鼠右側腓腸肌同一位點註射P-NCAM-Ab 20 U.註射前、後,動態測量大鼠腓腸肌肌肉的收縮彊度及濕重變化,併通過乙酰膽堿酯酶染色和氯化金染色觀察大鼠運動終闆及可視神經纖維的變化情況.結果 榦預後,正常對照組大鼠腓腸肌肌肉的收縮彊度隨時間延長而逐漸增加,BTX-A組和P-NCAM-Ab組則呈現齣先下降後上升的趨勢.與正常對照組同時間點比較,BTX-A組和P-NCAM-Ab組大鼠註射BTX-A後3d及1,2,4,6,8,10週時的腓腸肌肌肉收縮彊度均較弱(P＜0.05);與BTX-A組同時間點比較,除註射後3d及1週,P-NCAM-Ab組大鼠剩餘時間點腓腸肌肌肉的收縮彊度均較BTX-A組弱(P＜0.05).BTX-A組和P-NCAM-Ab組大鼠腓腸肌收縮彊度的恢複時間長于正常對照組(P＜0.05),且P-NCAM-Ab組的恢複時間長于BTX-A組(P＜0.05).BTX-A組和P-NCAM-Ab組大鼠腓腸肌濕重百分比隨時間增長呈現齣先下降後上升的趨勢,且註射後3d及1,2,4週,BTX-A組和P-NCAM-Ab組組間比較,差異有統計學意義(P＜0.05).註射BTX-A後1,2,4,8,12週,BTX-A組及P-NCAM-Ab組運動終闆染色均逐漸加深,但P-NCAM-Ab組大鼠運動終闆同時間點內染色均淺于BTX-A組.BTX-A組和P-NCAM-Ab組大鼠運動終闆暘性反應區域平均光密度值隨時間延長而逐漸增加,且P-NCAM-Ab組在第1,2,4,8,12週時的平均光密度值低于BTX-A組(P＜0.05).BTX-A組和P-NCAM-Ab組大鼠神經纖維數量的變化趨勢相似,除註射後3d、12週,2組剩餘時間點神經纖維數量與正常對照組比較,差異有統計學意義(P＜0.05),且2組剩餘時間點神經纖維數量間比較,差異亦有統計學意義(P＜0.05).結論 給予大鼠腓腸肌P-NCAM-Ab跼部註射後,可增彊BTX-A的生物學效應,併延長其單次註射後的療效持續時間.
목적 탐토다극륭신경세포점부분자항체(P-NCAM-Ab)대A형육독독소(BTX-A)생물학효응적영향.방법 선취웅성SD대서90지,안수궤수자표법장기분위정상대조조、BTX-A조、P-NCAM-Ab조,매조30지.급여BTX-A조화P-NCAM-Ab조대서우측비장기BTX-A 0.5 U(100μl)주사,정상대조조대서칙주사동등체적적생리염수,제3천시재P-NCAM-Ab조대서우측비장기동일위점주사P-NCAM-Ab 20 U.주사전、후,동태측량대서비장기기육적수축강도급습중변화,병통과을선담감지매염색화록화금염색관찰대서운동종판급가시신경섬유적변화정황.결과 간예후,정상대조조대서비장기기육적수축강도수시간연장이축점증가,BTX-A조화P-NCAM-Ab조칙정현출선하강후상승적추세.여정상대조조동시간점비교,BTX-A조화P-NCAM-Ab조대서주사BTX-A후3d급1,2,4,6,8,10주시적비장기기육수축강도균교약(P＜0.05);여BTX-A조동시간점비교,제주사후3d급1주,P-NCAM-Ab조대서잉여시간점비장기기육적수축강도균교BTX-A조약(P＜0.05).BTX-A조화P-NCAM-Ab조대서비장기수축강도적회복시간장우정상대조조(P＜0.05),차P-NCAM-Ab조적회복시간장우BTX-A조(P＜0.05).BTX-A조화P-NCAM-Ab조대서비장기습중백분비수시간증장정현출선하강후상승적추세,차주사후3d급1,2,4주,BTX-A조화P-NCAM-Ab조조간비교,차이유통계학의의(P＜0.05).주사BTX-A후1,2,4,8,12주,BTX-A조급P-NCAM-Ab조운동종판염색균축점가심,단P-NCAM-Ab조대서운동종판동시간점내염색균천우BTX-A조.BTX-A조화P-NCAM-Ab조대서운동종판양성반응구역평균광밀도치수시간연장이축점증가,차P-NCAM-Ab조재제1,2,4,8,12주시적평균광밀도치저우BTX-A조(P＜0.05).BTX-A조화P-NCAM-Ab조대서신경섬유수량적변화추세상사,제주사후3d、12주,2조잉여시간점신경섬유수량여정상대조조비교,차이유통계학의의(P＜0.05),차2조잉여시간점신경섬유수량간비교,차이역유통계학의의(P＜0.05).결론 급여대서비장기P-NCAM-Ab국부주사후,가증강BTX-A적생물학효응,병연장기단차주사후적료효지속시간.
Objective To investigate the impact of polyclonal neural cell adhesion molecule antibody (P-NCAM-Ab) on the potency of botulinum toxin A (BTX-A).Methods Ninety male Sprague-Dawley rats were randomly divided into 3 equal groups:a normal control group,a BTX-A group and a P-NCAM-Ab group.The rats in the normal control group were injected with 100 μl of saline solution in their right gastrocnemius,while those in the BTX-A and P-NCAM-Ab groups were injected with 100 μl of BTX-A (0.5 U).In addition,the rats in the P-NCAM-Ab group were also injected with 100 μl of P-NCAM-Ab (the dosage was 20 U) at the same site on the 3rd day after the BTX-A injection.The rats' gastrocnemius muscle strength was evaluated with a self-made system for evaluating neuromuscular function before and after the toxin injection,on the 3rd day,as well as 1,2,4,6,8,10 and 12 weeks after the BTX-A injection.Any wet weight changes in the muscles were observed,and immunochemistry methods were employed to observe any structural changes in the motor endplates and nerve fibers at the different time points.Results After the saline injection,the average gastrocnemius muscle strength of the control group increased with time,while strength in the BTX-A and P-NCAM-Ab groups demonstrated a decrease in strength followed by a gradual increase.The average gastrocnemius muscle strength of the rats in the BTX-A and P-NCAM-Ab groups was significantly lower than that of the control group at all time points.Compared with the BTX-A group,the muscle strength of the P-NCAM-Ab group rats decreased further.Strength recovery in the BTX-A and P-NCAM-Ab groups was significantly slower than in the control group.The wet weight percentage in the BTX-A and P-NCAM-Ab groups at first decreased and then recovered with time.After the BTX-A injection,the average wet weight percentage of the P-NCAM-Ab group rats was significantly lower than that of the BTX-A group after 3 days,and 1,2 and 4 weeks.Karnovsky-Roots AchE staining showed that the motor endplates' color in the BTX-A and P-NCAM-Ab groups deepened gradually,though the color of the P-NCAM-Ab group was lighter than that of the BTX-A group at each time point.The mean optical density of the motor endplates' positive reaction area increased with time in both groups,but the P-NCAM-Ab group was lower than that of the BTX-A group at 1,2,4,8 and 12 weeks.Counting the nerve fibers dyed by gold chloride showed similar trends with both experimental groups significantly different from the control group.Conclusion P-NCAM-Ab can increase the potency of BTX-A and prolong its action.
