利多卡因对急性脊髓损伤后白细胞炎症反应及自由基的影响
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摘要
急性脊髓损伤之后发生一系列病理生理改变，在这一系列病理生理反应中，嗜中性粒细胞起着重要的作用，嗜中性粒细胞主要存在于急性脊髓损伤(SCI)后出血和组织坏死区域，创伤后大量中性白细胞渗出，血管痉挛，导致无血灌流，长时间的无血流，血管壁结构破坏，更多白细胞渗出，释放活性物及各种溶组织酶，脊髓组织溶解坏死，故抗炎作用能减少组织的坏死。降低炎症反应的治疗对急性脊髓损伤后功能的恢复有积极意义。同时自由基在脊髓损伤后继发的病理损害中也起着重要作用，国外有报道证明利多卡因有保护脊髓血流的作用，国内研究表明利多卡因在急性脑挫伤动物模型中有抑制白细胞炎症反应的作用，但利多卡因对急性脊髓损伤动物模型损伤灶的白细胞炎症反应是否有抑制作用，国内外尚无报道。
目的
本研究对急性脊髓损伤大鼠模型进行早期利多卡因注射治疗，并分成6小时，3天，7天三个时间段取损伤局灶标本，进行试验组和对照组的髓过氧化物酶(MPO)和超氧化物岐化酶(SOD)值比较，并记录大鼠功能评分以判断功能恢复情况，以探讨利多卡因对急性脊髓损伤中急性炎症反应和自由基反应的作用。
方法
参照改良的Allen's重物打击法制备急性脊髓背侧损伤大鼠模型36只。按随机化原则将实验动物分成二组，分别为对照组和实验组。对照组18只大鼠，不使用利多卡因，于伤后6h、3d、7d取标本，每个时间点6只；实验组18只大鼠，使用利多卡因，于伤后6h、3d、7d取标本，三个时间点的例数各为6只；用髓过氧化物法(MPO法)测定损伤灶白细胞数目，用超氧化物歧化酶(SOD)法测定氧自由基反应产物。并进行功能评分(改良CBS法评估)。利用SPSS统计软件系统对数据进行分析。
结果
1.实验组MPO值在各时段均比对照组低，经t检验有显著意义。即试
验组白细胞炎症反应在各时段均比对照组轻。
2.实验组SOD值在各时段均比对照组高，经t检验有显著意义。即试
验组氧自由基反应产物在各时段均比对照组低。
3.实验组功能评分在各时段均比对照组高，经t检验有显著意义。即
试验组大鼠功能保留比对照组多。
4.经相关检验，MPO值与SOD值无显著相关，在各时段MPO值和功能
评分有显著相关性。
结论
1.在脊髓损伤后早期应用利多卡因对局灶的白细胞炎性反应有抑制作
用。且此抑制作用与功能评分有直线相关关系。进一步验证了利多卡因对
急性脊髓损伤后继发损害有预防作用。
2.通过本实验验证了利多卡因可以抑制脊髓损伤后自由基反，应。
3.利多卡因对急性脊髓损伤后局灶的白细胞炎症反应的抑制作用与利
多卡因对氧自由基反应的抑制作用之间没有相关性，说明二者是各自起作
用的。
There is a series of pathological and physiological changes after acute spinal cord injury (ASCI) in which neutrophils play a great role in it. Neutropils exist mainly in tissues which are bleeding or necrotic after ASCI. After ASCI, a great quantity of leucocytes exfiltrate and micro blood vessels spasm which can induce ischemic perfusion. If it continues, the structures of blood vessels'wall( VW) would be destroyed and much more leukocytes were exfiltrated, releasing active materials and various kinds of organized enzyme which can dissolve spinal cord tissues, so the function of antiinflammation can reduce the necrotic tissues. It is of great significance to inhibit inflammation after ASCI which can contribute to the spinal cord function recovery. In the same time, the free radical reaction is also play a role in the second injury after ASCI. Several studies report that lidocaine can protect the blood vessel, and some studies also show that lidocaine can inhibit the delivery of leukocyte to the contused br
ain tissues. However, there is no studies on whether lidocaine has the same functions on contused spinal cord tissues after ASCI.
Objective
Lidocain is injected into abdominal cavity after ASCI once a day. AT 6hours,3 days , 7days after ASCI, the specimen of the contused spinal cord were removed for analysis. We compare MPO value and SOD value between the control - group and the treated - group. Meanwhile the functional scores of the rats are recorded to approach the functions of lidocaine in the local leucocytic inflammation and the free radical reaction of contused spinal cord tissue.
Methods
36 animal models of acute spinal cord injury were established through free - fall impacting( modified Aliens method). The animals were separated into two groups by random. In the treated - group, 18 animals were subjected to the peritoneal injection of lidocaine (1. 5mg/kg) once a day. All animals were sacrificed and spinal cord removed for analysis after 6 ~8hours,3days,7days respectively. The MPO method was taken to testify the number of leucocytes of contused spinal cord and SOD method was taken to testify the products of free radical reaction. In the same time, the functional sores were recorded, then all the data were analysis by SPSS.
Results
1. The MPO value of treated - group is lower than that of control - group in each time point which is verified by t test. That is , there is more obvious leuco-cytic inflammation in control group than in lidocaine - treated group.
2. The SOD value of treated - group is higher than that of control - group in each time point which is verified by t test. That is , there is less products of free radical reaction in the treated -group.
3. Functional scores of rats in treated group is higher than contol group and it is testified by t test. That is, the function of treated - group is recovered better.
4. Through correlational test, MPO value is not related with SOD value and MPO value is related significantly with functional score in each group.
Conclusion
1. We discovered that lidocaine can inhibit the delivery of leukocyte to the contused spinal cord tissues , and the function of lidocaine has linear correlation with functional score. We testify the protect function of lidocain in the second
injury of ASCI.
2. Lidocaine can inhibit the free radical reaction after ASCI.
3. The function of preventing leucocytic inflammation has no relationship with the function of preventing free radical reaction, so the two functions of lido-caine are acting repeclively.
目的
本研究对急性脊髓损伤大鼠模型进行早期利多卡因注射治疗，并分成6小时，3天，7天三个时间段取损伤局灶标本，进行试验组和对照组的髓过氧化物酶(MPO)和超氧化物岐化酶(SOD)值比较，并记录大鼠功能评分以判断功能恢复情况，以探讨利多卡因对急性脊髓损伤中急性炎症反应和自由基反应的作用。
方法
参照改良的Allen's重物打击法制备急性脊髓背侧损伤大鼠模型36只。按随机化原则将实验动物分成二组，分别为对照组和实验组。对照组18只大鼠，不使用利多卡因，于伤后6h、3d、7d取标本，每个时间点6只；实验组18只大鼠，使用利多卡因，于伤后6h、3d、7d取标本，三个时间点的例数各为6只；用髓过氧化物法(MPO法)测定损伤灶白细胞数目，用超氧化物歧化酶(SOD)法测定氧自由基反应产物。并进行功能评分(改良CBS法评估)。利用SPSS统计软件系统对数据进行分析。
结果
1.实验组MPO值在各时段均比对照组低，经t检验有显著意义。即试
验组白细胞炎症反应在各时段均比对照组轻。
2.实验组SOD值在各时段均比对照组高，经t检验有显著意义。即试
验组氧自由基反应产物在各时段均比对照组低。
3.实验组功能评分在各时段均比对照组高，经t检验有显著意义。即
试验组大鼠功能保留比对照组多。
4.经相关检验，MPO值与SOD值无显著相关，在各时段MPO值和功能
评分有显著相关性。
结论
1.在脊髓损伤后早期应用利多卡因对局灶的白细胞炎性反应有抑制作
用。且此抑制作用与功能评分有直线相关关系。进一步验证了利多卡因对
急性脊髓损伤后继发损害有预防作用。
2.通过本实验验证了利多卡因可以抑制脊髓损伤后自由基反，应。
3.利多卡因对急性脊髓损伤后局灶的白细胞炎症反应的抑制作用与利
多卡因对氧自由基反应的抑制作用之间没有相关性，说明二者是各自起作
用的。
There is a series of pathological and physiological changes after acute spinal cord injury (ASCI) in which neutrophils play a great role in it. Neutropils exist mainly in tissues which are bleeding or necrotic after ASCI. After ASCI, a great quantity of leucocytes exfiltrate and micro blood vessels spasm which can induce ischemic perfusion. If it continues, the structures of blood vessels'wall( VW) would be destroyed and much more leukocytes were exfiltrated, releasing active materials and various kinds of organized enzyme which can dissolve spinal cord tissues, so the function of antiinflammation can reduce the necrotic tissues. It is of great significance to inhibit inflammation after ASCI which can contribute to the spinal cord function recovery. In the same time, the free radical reaction is also play a role in the second injury after ASCI. Several studies report that lidocaine can protect the blood vessel, and some studies also show that lidocaine can inhibit the delivery of leukocyte to the contused br
ain tissues. However, there is no studies on whether lidocaine has the same functions on contused spinal cord tissues after ASCI.
Objective
Lidocain is injected into abdominal cavity after ASCI once a day. AT 6hours,3 days , 7days after ASCI, the specimen of the contused spinal cord were removed for analysis. We compare MPO value and SOD value between the control - group and the treated - group. Meanwhile the functional scores of the rats are recorded to approach the functions of lidocaine in the local leucocytic inflammation and the free radical reaction of contused spinal cord tissue.
Methods
36 animal models of acute spinal cord injury were established through free - fall impacting( modified Aliens method). The animals were separated into two groups by random. In the treated - group, 18 animals were subjected to the peritoneal injection of lidocaine (1. 5mg/kg) once a day. All animals were sacrificed and spinal cord removed for analysis after 6 ~8hours,3days,7days respectively. The MPO method was taken to testify the number of leucocytes of contused spinal cord and SOD method was taken to testify the products of free radical reaction. In the same time, the functional sores were recorded, then all the data were analysis by SPSS.
Results
1. The MPO value of treated - group is lower than that of control - group in each time point which is verified by t test. That is , there is more obvious leuco-cytic inflammation in control group than in lidocaine - treated group.
2. The SOD value of treated - group is higher than that of control - group in each time point which is verified by t test. That is , there is less products of free radical reaction in the treated -group.
3. Functional scores of rats in treated group is higher than contol group and it is testified by t test. That is, the function of treated - group is recovered better.
4. Through correlational test, MPO value is not related with SOD value and MPO value is related significantly with functional score in each group.
Conclusion
1. We discovered that lidocaine can inhibit the delivery of leukocyte to the contused spinal cord tissues , and the function of lidocaine has linear correlation with functional score. We testify the protect function of lidocain in the second
injury of ASCI.
2. Lidocaine can inhibit the free radical reaction after ASCI.
3. The function of preventing leucocytic inflammation has no relationship with the function of preventing free radical reaction, so the two functions of lido-caine are acting repeclively.
引文
1. Carlson SL et al. Exp Neurol 1998 May; 151(1): 77-88.
2. Tator CH. J Neurosurg, 1991, 75: 15-16.
3. Brachen MB, Holford TR. Effects of timing on recovery of segmental and longtract neurologic function in NASCIS 2. J Neurosurg, 1993, 79: 500～507。Nokels R, Uong W. Pharmacologic strategies in the treaqtment of sxpwrimental spinal cord infuries. J Neurotrauma, 1992, 9(1s): 211～217.
4. Shaoting Xu. China J Orthop, May 1997, Vol. 17, No. 5: 340.
5. Ritchie JM et al. Annu Rev Pharmacol, 1966; 6: 405 Seeman P et al. Pharmacol Rev, 1972; 24: 583.
6．邵阳。创伤早期免疫炎性反应与脊髓继发性损伤．J Trauma Surg，2002，Vol．4．No．3．
7．索广文。脊髓损伤后超早期静脉用利多卡因的效果。首届全国创伤学术会议论文汇编。重庆。1988，112．
8. Arbtur IK, Delbert EE, David CL, et al. Effect of intravenous Lidocaine on experimental spinal cord injury, J Neurosurg. 1984; 60: 595～601.
9．刘力良。利多卡因对挫伤脑组织白细胞炎症反应的影响。中华实验外科杂志，2002，19：371．
10. Edward LH, et al, Central nervous system trauma. 1986, 3: 2.
11．王建中，周庆芬，索广文。利多卡因与自由基在脊髓损伤中关系的探讨。颈腰痛杂志。1998，19(3)：179～180．
12. Arbtur IK, Delbert EE, David CL, et al. Effect of intravenous Lidocaine on experimental spinal cord injury, J Neurosurg. 1984; 60: 595～601.
13. Seeman P et al. Pharmacol Rev,1972;24:583 Nishina et al. Anesthesiology,1998;88(5): 1300.
14. Kobrine AI et al. J Neurosurg 1984 Mar;60(3): 595-601.
15．胥少汀等。脊髓损伤基础与临床，2002，vol 9，298．
2. Tator CH. J Neurosurg, 1991, 75: 15-16.
3. Brachen MB, Holford TR. Effects of timing on recovery of segmental and longtract neurologic function in NASCIS 2. J Neurosurg, 1993, 79: 500～507。Nokels R, Uong W. Pharmacologic strategies in the treaqtment of sxpwrimental spinal cord infuries. J Neurotrauma, 1992, 9(1s): 211～217.
4. Shaoting Xu. China J Orthop, May 1997, Vol. 17, No. 5: 340.
5. Ritchie JM et al. Annu Rev Pharmacol, 1966; 6: 405 Seeman P et al. Pharmacol Rev, 1972; 24: 583.
6．邵阳。创伤早期免疫炎性反应与脊髓继发性损伤．J Trauma Surg，2002，Vol．4．No．3．
7．索广文。脊髓损伤后超早期静脉用利多卡因的效果。首届全国创伤学术会议论文汇编。重庆。1988，112．
8. Arbtur IK, Delbert EE, David CL, et al. Effect of intravenous Lidocaine on experimental spinal cord injury, J Neurosurg. 1984; 60: 595～601.
9．刘力良。利多卡因对挫伤脑组织白细胞炎症反应的影响。中华实验外科杂志，2002，19：371．
10. Edward LH, et al, Central nervous system trauma. 1986, 3: 2.
11．王建中，周庆芬，索广文。利多卡因与自由基在脊髓损伤中关系的探讨。颈腰痛杂志。1998，19(3)：179～180．
12. Arbtur IK, Delbert EE, David CL, et al. Effect of intravenous Lidocaine on experimental spinal cord injury, J Neurosurg. 1984; 60: 595～601.
13. Seeman P et al. Pharmacol Rev,1972;24:583 Nishina et al. Anesthesiology,1998;88(5): 1300.
14. Kobrine AI et al. J Neurosurg 1984 Mar;60(3): 595-601.
15．胥少汀等。脊髓损伤基础与临床，2002，vol 9，298．