Netrin-1、Slit2在夹脊电针结合神经松动术调节兔坐骨神经损伤后Rho GTPases失衡的作用

doi:10.3969/j.issn.1006-9771.2022.08.007

《中国康复理论与实践》 ›› 2022, Vol. 28 ›› Issue (8): 914-926.doi: 10.3969/j.issn.1006-9771.2022.08.007

Netrin-1、Slit2在夹脊电针结合神经松动术调节兔坐骨神经损伤后Rho GTPases失衡的作用

张立¹,吴珊红²,赵乐乐³,王艳¹()

1.黑龙江中医药大学附属第二医院,黑龙江哈尔滨市 150001
2.黑龙江中医药大学,黑龙江哈尔滨市 150040
3.浙江省中医院,浙江杭州市 310003

收稿日期:2022-02-10 修回日期:2022-05-20 出版日期:2022-08-25 发布日期:2022-08-30
通讯作者: 王艳 E-mail:swallow-1113@163.com
作者简介:张立(1975-),女,汉族,黑龙江哈尔滨市人,博士,副主任医师,主要研究方向：神经系统疾病的常见功能障碍的中医康复治疗。|王艳(1967-),女,汉族,博士,教授,博士研究生导师,主要研究方向：周围神经损伤康复及儿童康复。
基金资助:
国家自然科学基金面上项目(816740077);黑龙江中医药大学创新人才基金项目(2018RCL10)

Role of Netrin-1 and Slit2 in regulating the imbalance of Rho GTPases after Jiaji electroacupuncture combined with nerve mobilization for sciatic nerve injury in rabbits

ZHANG Li¹,WU Shanhong²,ZHAO Lele³,WANG Yan¹()

1. The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150001, China
2. Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, China
3. Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang 310003, China

Received:2022-02-10 Revised:2022-05-20 Published:2022-08-25 Online:2022-08-30
Contact: WANG Yan E-mail:swallow-1113@163.com
Supported by:
National Natural Science Foundation of China (General)(816740077);Fund for Innovative Talents of Heilongjiang University of Chinese Medicine(2018RCL10)

摘要/Abstract

摘要：

目的观察夹脊电针结合神经松动术疗法对兔坐骨神经损伤后神经传导速度及 Netrin-1、Slit2、Rho GTPases表达的影响。

方法将216只新西兰家兔随机分为正常对照组、病毒空载组、夹脊电针结合神经松动术组、Netrin-1组、Slit2组、Netrin-1+Slit2腺病毒结合组,按术后1、2、4周三个时间点分为3个亚组,每个亚组12只。钳夹法造兔左侧坐骨神经Sunderland Ⅲ度损伤模型。正常对照组无干预;各病毒组在模型制备时完成目的基因转染病毒注射;夹脊电针结合神经松动术组术后3 d即进行夹脊电针及神经松动术治疗。肌电图测量兔坐骨神经传导速度,取损伤坐骨神经和L_4-6脊髓,荧光实时定量聚合酶链反应检测Netrin-1 mRNA、Slit2 mRNA表达,Western blotting检测Rac1、Cdc42、RhoA蛋白表达。

结果术后1、2、4周,夹脊电针结合神经松动术组、Netrin-1+Slit2腺病毒结合组坐骨神经神经传导速度高于Netrin-1组和Slit2组(P < 0.05);电针结合神经松动术组、Netrin-1+Slit2腺病毒结合组Netrin-1和Slit2 mRNA表达高于正常对照组、病毒空载组(P < 0.05);电针结合神经松动术组和Netrin-1+Slit2腺病毒结合组Rac1、Cdc42蛋白表达高于Netrin-1组、Slit2组和病毒空载组(P < 0.05),而RhoA蛋白表达低于Netrin-1组、Slit2组和病毒空载组(P < 0.05)。

结论夹脊电针结合神经松动术促进轴突再生可能是通过调节Netrin-1、Slit2的表达,恢复 Rho GTPases酶系统失衡状态,重组细胞骨架,促进周围神经损伤后的再生。

关键词: 坐骨神经, 夹脊电针结合神经松动术, Netrin-1, Slit2, Rho GTPase

Abstract:

Objective To observe the effect of Jiaji electroacupuncture combined with neurodynamic mobilization on nerve conduction velocity and the expression of Netrin-1, Slit2 and Rho GTPases after sciatic nerve injury in rabbits.

Methods A total of 216 New Zealand rabbits were randomly divided into nomal control group (NC), vector virus group (VV), Jiaji electroacupuncture combined with neurodynamic mobilization group (EN), Netrin-1 group (N1), Slit2 group (S2) and N1+S2 group. Each group was divided into three subgroups according to the postoperative treatment time points (one, two and four weeks), with twelve rabbits in each subgroup. The rabbit model of Sunderland Ⅲ degree injury of the left sciatic nerve was established by clamping method. There was no intervention in NC, and virus was injected during the preparation of the model. Jiaji electroacupuncture and neurodynamic mobilization were administrated three days after operation in EN group. Nerve conduction velocity of sciatic nerve was measured with electromyography. The sciatic nerve and L_4-6 spinal cords were obtained, the expression of Netrin-1 and Slit2 mRNA were detected real-time quantitative polymerase chain reaction and immunofluorescence double staining, and the expression of Rac1, Cdc42 and RhoA protein were observed via Western blotting.

Results One, two and four weeks after modeling, the nerve conduction velocity was more in EN group and N1+S2 group than in N1 group and S2 group (P< 0.05); the Netrin-1 and Slit2 mRNA expression were higher in the EN group and N1+S2 group than in the VV group and NC group (P< 0.05); the protein expression of Rac1 and Cdc42 were higher, and the protein expression of RhoA was lower in EN group and N1+S2 group than in N1 group, S2 group and VV group (P< 0.05).

Conclusion Jiaji electroacupuncture combined with nerve mobilization may promote the axonal regeneration by regulating the expression of Netrin-1 and Slit2, adjusting the imbalance of Rho GTPases enzyme system, and then promoting cytoskeleton reorganization and peripheral nerve regeneration after injury.

Key words: sciatic nerve, Jiaji electroacupuncture combined with neurodymanic mobilization, Netrin-1, Slit2, Rho GTPase

中图分类号:

R745.4

张立,吴珊红,赵乐乐,王艳. Netrin-1、Slit2在夹脊电针结合神经松动术调节兔坐骨神经损伤后Rho GTPases失衡的作用[J]. 《中国康复理论与实践》, 2022, 28(8): 914-926.

ZHANG Li,WU Shanhong,ZHAO Lele,WANG Yan. Role of Netrin-1 and Slit2 in regulating the imbalance of Rho GTPases after Jiaji electroacupuncture combined with nerve mobilization for sciatic nerve injury in rabbits[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(8): 914-926.

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组别	n	术后1周	术后2周	术后4周
正常对照组	12	55.005±3.874	53.375±3.644	53.051±3.628
病毒空载组	12	40.105±3.145^a	29.865±3.956^a	27.465±3.953^a
夹脊电针结合神经松动术组	12	35.234±2.665^a,b	43.605±2.805^a,b	48.445±3.517^a,b
Netrin-1组	12	28.654±2.543^a,b,c	37.445±3.825^a,b,c	39.976±3.263^a,b,c
Slit2组	12	28.774±2.955^a,b,c	36.765±4.005^a,b,c	39.245±4.014^a,b,c
Netrin-1+Slit2腺病毒结合组	12	35.225±3.133^a,b,d,e	44.160±3.958^a,b,d,e	46.914±3.421^a,b,d,e
F值		120.507	56.166	73.892
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	1.002±0.015	1.001±0.015	1.016±0.075
病毒空载组	12	1.265±0.111^a	1.415±0.206^a	1.525±0.284^a
夹脊电针结合神经松动术组	12	1.685±0.216^a,b	1.725±0.120^a,b	1.785±0.234^a,b
Netrin-1组	12	2.114±0.276^a,b,c	2.050±0.287^a,b,c	2.345±0.362^a,b,c
Slit2组	12	1.314±0.194^a,c,d	1.333±0.159^a,c,d	1.549±0.294^a,c,d
Netrin-1+Slit2腺病毒结合组	12	1.885±0.235^a,b,c,e	2.014±0.317^a,b,c,e	2.214±0.302^a,b,c,e
F值		55.633	46.449	37.734
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	0.996±0.014	1.000±0.0124	1.004±0.085
病毒空载组	12	1.294±0.117^a	1.314±0.145^a	1.525±0.244
夹脊电针结合神经松动术组	12	1.665±0.234^a,b	1.814±0.254^a,b	1.915±0.243^a,b
Netrin-1组	12	2.284±0.267^a,b,c	2.455±0.383^a,b,c	2.585±0.364^a,b,c
Slit2组	12	1.245±0.184^a,c,d	1.264±0.163^a,c,d	1.479±0.226^a,c,d
Netrin-1+Slit2腺病毒结合组	12	2.125±0.294^a,b,c,e	2.265±0.274^a,b,c,e	2.454±0.313^a,b,c,e
F值		73.527	74.202	65.746
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	0.971±0.088	0.977±0.089	1.009±0.113
病毒空载组	12	1.286±0.117^a	1.345±0.145^a	1.415±0.126^a
夹脊电针结合神经松动术组	12	1.585±0.165^a,b	1.614±0.165^a,b	1.654±0.147^a,b
Netrin-1组	12	1.325±0.150^a,c	1.337±0.135^a,c	1.465±0.135^a,c
Slit2组	12	1.877±0.185^a,b,c,d	1.885±0.183^a,b,c,d	1.945±0.225^a,b,c,d
Netrin-1+Slit2腺病毒结合组	12	1.914±0.206^a,b,c,d	1.935±0.188^a,b,c,d	1.954±0.250^a,b,c,d
F值		65.368	67.645	50.839
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	0.984±0.075	0.996±0.083	1.012±0.055
病毒空载组	12	1.425±0.094^a	1.465±0.100^a	1.480±0.113^a
夹脊电针结合神经松动术组	12	1.685±0.132^a,b	1.745±0.192^a,b	1.765±0.249^a,b
Netrin-1组	12	1.364±0.084^a,c	1.394±0.105^a,c	1.406±0.116^a,c
Slit2组	12	2.374±0.273^a,b,c,d	2.464±0.315^a,b,c,d	2.475±0.327^a,b,c,d
Netrin-1+Slit2腺病毒结合组	12	2.354±0.235^a,b,c,d	2.415±0.342^a,b,c,d	2.425±0.315^a,b,c,d
F值		134.582	93.423	82.778
P值		< 0.001	< 0.001	< 0.001

Netrin-1、Slit2在夹脊电针结合神经松动术调节兔坐骨神经损伤后Rho GTPases失衡的作用

Role of Netrin-1 and Slit2 in regulating the imbalance of Rho GTPases after Jiaji electroacupuncture combined with nerve mobilization for sciatic nerve injury in rabbits

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组别	n	术后1周	术后2周	术后4周
正常对照组	12	0.995±0.050	1.001±0.021	1.016±0.062
病毒空载组	12	0.425±0.033^a	0.354±0.043^a	0.296±0.044^a
夹脊电针结合神经松动术组	12	0.785±0.032^a,b	0.692±0.029^a,b	0.745±0.043^a,b
Netrin-1组	12	0.530±0.023^a,b,c	0.505±0.052^a,b,c	0.484±0.049^a,b,c
Slit2组	12	0.433±0.035^a,c,d	0.388±0.041^a,c,d	0.310±0.053^a,c,d
Netrin-1+Slit2腺病毒结合组	12	0.680±0.030^a,b,c,d,e	0.705±0.028^a,b,d,e	0.730±0.046^a,b,d,e
F值		490.986	530.711	352.238
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	0.995±0.051	0.994±0.250	0.997±0.062
病毒空载组	12	0.322±0.072^a	0.240±0.010^a	0.225±0.035^a
夹脊电针结合神经松动术组	12	0.825±0.023^a,b	0.765±0.025^a,b	0.75±0.033^a,b
Netrin-1组	12	0.480±0.021^a,b,c	0.625±0.043^a,b,c	0.424±0.051^a,b,c
Slit2组	12	0.354±0.0832^a,c,d	0.215±0.013^a,c,d	0.201±0.021^a,c,d
Netrin-1+Slit2腺病毒结合组	12	0.717±0.052^a,b,c,d,e	0.794±0.038^a,b,d,e	0.615±0.042^a,b,c,d,e
F值		295.530	109.746	639.603
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	0.995±0.060	0.995±0.040	1.002±0.035
病毒空载组	12	0.515±0.063^a	0.454±0.054^a	0.415±0.083^a
夹脊电针结合神经松动术组	12	0.874±0.100^a,b	0.754±0.113^a,b	0.760±0.153^a,b
Netrin-1组	12	0.677±0.052^a,b,c	0.620±0.065^a,b,c	0.585±0.073^a,b
Slit2组	12	0.530±0.110^a,c,d	0.406±0.083^a,c,d	0.375±0.076^a,c,d
Netrin-1+Slit2腺病毒结合组	12	0.745±0.120^a,b,c,d,e	0.908±0.140^a,b,c,d,e	0.877±0.092^a,b,c,d,e
F值		60.425	84.290	89.855
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	1.031±0.092	1.027±0.110	0.985±0.120
病毒空载组	12	0.484±0.074^a	0.414±0.086^a	0.434±0.072^a
夹脊电针结合神经松动术组	12	0.848±0.050^a,b	0.734±0.023^a,b	0.834±0.150^a,b
Netrin-1组	12	0.631±0.012^a,b,c	0.620±0.011^a,b,c	0.607±0.013^a,b,c
Slit2组	12	0.525±0.070^a,c,d	0.374±0.065^a,c,d	0.394±0.120^a,c,d
Netrin-1+Slit2腺病毒结合组	12	0.727±0.073^a,b,c,d,e	0.837±0.010^a,b,c,d,e	0.725±0.085^a,b,c,d,e
F值		118.939	180.41	55.387
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	1.011±0.302	1.000±0.287	0.995±0.153
病毒空载组	12	4.820±0.119^a	4.654±0.189^a	6.490±0.158^a
夹脊电针结合神经松动术组	12	1.837±0.129^a,b	1.452±0.0848^a,b	1.883±0.199^a,b
Netrin-1组	12	4.808±0.099^a,c	4.420±0.167^a,c	6.474±0.117^a,c
Slit2组	12	3.561±0.118^a,b,c,d	2.762±0.178^a,b,c,d	2.610±0.109^a,b,c,d
Netrin-1+Slit2腺病毒结合组	12	1.320±0.107^a,b,c,d,e	1.810±0.196^a,b,c,d,e	1.691±0.168^a,b,c,d,e
F值		1386.867	766.156	3130.581
P值		< 0.001	< 0.001	< 0.001

组别	n	术后1周	术后2周	术后4周
正常对照组	12	1.005±0.053	1.010±0.076	1.002±0.179
病毒空载组	12	2.421±0.214^a	2.714±0.254^a	3.142±0.318^a
夹脊电针结合神经松动术组	12	1.510±0.184^a,b	1.311±0.156^a,b	1.470±0.288^a,b
Netrin-1组	12	2.412±0.098^a,c	2.603±0.147^a,c	3.011±0.207^a,c
Slit2组	12	2.103±0.117^a,b,c,d	1.813±0.229^a,b,c,d	2.512±0.189^a,b,c,d
Netrin-1+Slit2腺病毒结合组	12	1.384±0.046^a,b,c,d,e	1.491±0.219^a,b,c,d,e	1.222±0.087^a,b,c,d,e
F值		232.092	162.279	236.881
P值		< 0.001	< 0.001	< 0.001

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