不同途径注射鼠神经生长因子对脑瘫患儿运动发育、脑血流动力学及生化代谢的影响

Effect of injecting mouse nerve growth factor in different ways on motor development, cerebral hemodynamics and biochemical metabolism in children with cerebral palsy

目的:比较穴位注射与肌内注射鼠神经生长因子(mNGF)对脑性瘫痪(CP)患儿粗大运动功能发育的疗效,并探讨其治疗机制。方法:将63例CP患儿随机分为观察组(32例,脱落4例)和对照组(31例,脱落3例)。两组均采用常规康复训练治疗,对照组肌内注射mNGF(18μg/2 mL),观察组于心俞、肝俞、脾俞、肾俞、三焦俞、神庭、百会、风府、大椎等穴行穴位注射mNGF,每次交替选取5~6个穴位,每穴0.3~0.5m L,总量18μg/2 mL,均隔日1次,疗程为6个月。治疗前后以粗大运动功能分级系统(GMFCS)评价两组患儿脑功能发育状况;治疗前(T0)、治疗2个月(T2)、4个月(T4)和6个月(T6)采用粗大运动功能评估量表88项(GMFM-88)评价运动功能;治疗前后检测大脑前动脉(ACA)和大脑中动脉(MCA)的收缩期峰流速(Vs)、平均血流速(Vm)和血管阻力指数(RI);治疗前后采用MAGNETOM Skyra3.0T磁共振成像系统行磁共振波谱(MRS)检测,分析基底节、丘脑、侧脑室前后角旁白质N-乙酰天门冬氨酸(NAA)、胆碱复合物(Cho)、乳酸(Lac)和肌酸(Cr)水平。结果:与治疗前比较,治疗后观察组GMFCS分级明显改善(P<0.05);治疗后两组患儿GMFCS分级比较,差异无统计学意义(P>0.05),但治疗后观察组粗大运动功能发育倾向于良好至少一个等级的可能性是对照组的3.142倍(P<0.05)。治疗2、4、6个月后,两组GMFM-88评分均呈上升趋势(P<0.01),且观察组升高幅度大于对照组(P<0.05)。与治疗前比较,治疗后两组ACA和MCA的Vs、Vm升高,RI降低(P<0.01),脑组织NAA/Cr升高、Cho/Cr和Lac/Cr降低(P<0.01),且治疗后观察组ACA和MCA的Vs、Vm及脑组织NAA/Cr高于对照组(P<0.05),ACA和MCA的RI及脑组织Cho/Cr和Lac/Cr低于对照组(P<0.05)。结论:穴位注射mNGF对CP患儿粗大运动功能发育的改善优于肌内注射mNGF,其机制可能是穴位注射疗法叠加了穴位作用和药物的靶向治疗作用,可有效改善脑血流动力学状况和脑神经物质的代谢。

Objective To compare the effect of acupoint injection and intramuscular injection with mouse nerve growth factor(mNGF)on gross motor function development of children with cerebral palsy(CP),and explore the treatment mechanism.Methods A total of 63 children with CP were randomly divided into an observation group(32 cases,4 cases dropped off)and a control group(31 cases,3 cases dropped off).Based on the routine rehabilitation therapy,the control group received intramuscular injection of mNGF(18μg/2 mL),and the observation group received acupoint injection of mNGF at Xinshu(BL 15),Ganshu(BL 18),Pishu(BL 20),Shenshu(BL 23),Sanjiaoshu(BL 22),Shenting(GV 24),Baihui(GV 20),Fengfu(GV 16),Dazhui(GV 14),etc.Of them,5-6 acupoints alternately were selected each time,and each acupoint was given 0.3-0.5 mL,totally 18μg/2 mL.Both treatment were carried out once every other day for six months.Before and after treatment,the children’s development of brain function was assessed using gross motor function classification system(GMFCS).Before treatment(T0),after 2(T2),4(T4)and 6(T6)months of treatment,the motor function was evaluated by gross motor function measure(GMFM-88).The systolic peak velocity(Vs),mean velocity(Vm)and vascular resistance index(RI)of anterior cerebral artery(ACA)and middle cerebral artery(MCA)were measured,and the level of N-acetyl aspartate acid(NAA),choline(Cho),lactate(Lac)and creatine(Cr)from the basal ganglia,thalamus and periventricular white mater were detected by magnetic resonance spectroscopy(MRS)technology with MAGNETOM Skyra3.0 T magnetic resonance imaging system before and after treatment.Results Compared with before treatment,the GMFCS classification of the observation group after treatment was significantly improved(P<0.05);after treatment,the difference of GMFCS classification between the two groups was not significant(P>0.05),however,the observation group had a 3.142 times of feasibility for good gross motor function development by more than level 1 compared to the control group(P<0.05).After 2,4,and 6 months of treatment,the GMFM-88 scores of the two groups showed an upward trend(P<0.01),and the increase of the observation group was greater than that of the control group(P<0.05).Compared with before treatment,in the ACA and MCA,the Vs and Vm increased,RI decreased in both groups after treatment(P<0.01),and in the brain,NAA/Cr increased,Cho/Cr and Lac/Cr decreased(P<0.01),and after treatment,the Vs,Vm of ACA and MCA and NAA/Cr of brain in the observation group were higher than those in the control group(P<0.05),and the RI of ACA and MCA and Cho/Cr and Lac/Cr of brain in the observation group were lower than those in the control group(P<0.05).Conclusion The mNGF acupoint injection has a better effect on the gross motor function in the children with cerebral palsy compared with the intramuscular injection,and the mechanism may be associated with exhibiting the double effects of acupoint effect and the targeting therapy of drug,which can effectively improve the cerebral hemodynamics and the metabolism of cerebral nervous substances.