A型肉毒毒素在额部皮肤软组织扩张中的应用
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摘要
研究背景与目的:额部扩张皮瓣具有与面部皮肤色泽相近、就近转移、血运丰富等优点被广泛应用于面颈部外伤、瘢痕、肿瘤及先天畸形等的治疗中,并成为鼻再造的首选方法。由于额部特殊的解剖结构,扩张器要植入到额肌下,因此,额部皮肤软组织扩张具有以下特点:①扩张器在注水扩张的过程中要克服来自表面皮肤及额肌的双重阻力,使注水速度减慢,扩张时间延长;②注水的过程中常出现局部疼痛、头痛、恶心等症状,迫使每次注水量减少,注水间隔时间延长;③带额肌的额部扩张皮瓣对于颜面部的修复来说也显较厚;④额部扩张皮瓣容易发生回缩。基于以上原因,我们提出使用A型肉毒毒素注射于额肌,可使额肌松弛麻痹、萎缩,但是否能达到缩短扩张时间、使皮瓣变薄和减轻扩张器注水时疼痛的作用,对此我们进行了动物实验及临床研究。
第一部分动物实验研究
实验一A型肉毒毒素应用于额部皮肤软组织扩张的动物实验研究
方法:选用6只小型猪作为实验动物,于其两侧胸腹部作网格样文身标记;一侧胸腹部皮肌注射A型肉毒毒素,另一侧注射生理盐水作为对照;两侧皮肌下植入200ml扩张器;扩张器每次注水量以扩张器囊内压达90mmHg为标准,每周注水两次,比较两侧注水前基础囊内压、每次注水量、扩张时间、扩张面积、皮瓣即时及远期回缩,并进行组织学及电镜检测。
结果:
1.实验组平均注水时间为28±4.5天,对照组为42±3.5天,有显著差异(P＜0.01);
2.实验组平均注水8±0.5次,每次注水量为26.1±3.5ml;对照组平均注水12±0.8次,每次注水量为16.7±0.9ml,两组间有显著差异(P＜0.01);
3.实验组平均基础囊内压为3.4±0.6mmHg,对照组为10.1±0.8mmHg,两者有显著差异(P＜0.01);
4.实验组扩张中心面积平均增加69%,整个扩张面积增加58%;对照组扩张中心面积增加57%,整个扩张面积增加42%,有显著性差异(P＜0.01);
5.实验组扩张皮瓣即时回缩率,无论从长度、宽度,还是面积来说,均小于对照组(P＜0.01);
6.皮瓣转移后早期实验组皮瓣回缩小于对照组(P＜0.05),中后期无明显差异(P＞0.05);
7.组织学检测显示两组皮瓣在表皮及真皮形态结构上无差别,实验组皮肌出现萎缩,电镜显示明暗带模糊,Z线排列弯曲、不规则,转移6周后出现肌细胞变性坏死。
实验二A型肉毒毒素注射对额部扩张皮瓣生物力学特性的影响
方法:选用4只小型猪作为实验动物,于其胸腹部作网格样文身标记;一侧皮肌注射A型肉毒毒素,另一侧注射生理盐水作为对照;两侧皮肌下植入200ml扩张器;扩张器每次注水20ml,每周注水两次;注水完成后,切取全层扩张皮瓣,去除包膜,在Instron4302万能材料试验机上对皮瓣试件进行应力—应变、应力松弛和蠕变性能检测。
结果:实验组扩张皮瓣的应力—应变、应力松弛及蠕变性能均优于对照组。
第二部分A型肉毒毒素在额部皮肤软组织扩张中的临床应用研究
方法:临床研究以6例患者进行额部自身对照研究,即平分额部扩张器植入区,一侧额肌注射A型肉毒毒素,另一侧作为对照,测量注水时间,评价注水时的疼痛指标,比较皮瓣厚度,观察临床疗效。
结果:平均注水时间为52天;注水时实验侧疼痛指标小于对照侧;注水过程中实验侧扩张速度及扩张面积大于对照侧;实验侧扩张皮瓣厚度小于对照侧;未出现A型肉毒毒素相关毒副作用;临床效果良好。
结论:
1.应用A型肉毒毒素可以使额部扩张阻力减小,扩张速度加快,扩张时间缩短;
2.应用A型肉毒毒素可以减轻额部扩张器注水时的疼痛,加快扩张速度,减轻患者心理负担;
3.应用A型肉毒毒素可以增加额部软组织扩张的有效扩张面积;
4.应用A型肉毒毒素可以减少额部扩张皮瓣的即时及早期回缩,有利于切口愈合,减少瘢痕形成;
5.应用A型肉毒毒素可以提高额部扩张皮瓣的生物力学性能;
6.应用A型肉毒毒素可以使额部扩张皮瓣变薄,有利于颜面部缺损的修复,可以取得良好的临床效果。
Background and Objective: The forehead expanded flap has been extensively used in therapy of facial trauma, scar, tumor and congenital deformity, because it have obvious advantages such as resembled color, abundant blood supply, and easy to be transferred. The forehead soft tissue expansion has become the best method for nasal reconstruction. However, the forehead anatomy demand the expander is implanted beneath the forehead muscle. So, the forehead soft tissue expansion is different from other region, as following: both skin and forehead muscle limit the expansion, prolong the therapy time; the patient feel headache and nausea while inflating, which slow the velocity of inflation; the forehead expanded flap, including the forehead muscle, is thick for the face; the forehead expanded flap tend to retraction. Therefore, we used the botulinum toxin A to make the forehead muscle paralysis and atrophy. The goal of our animal studies and clinical research is to investigate if the botulinum toxin A may reduce the expansion period, eliminate the pain and thin the expanded flap.
PartⅠAnimal ExperimentsExperimentⅠ
Animal experiment of using botulinum toxin A inforehead soft tissue expansion
Methods: The six guinea pigs were the model of animal studies. Mark the bilateral chest and abdomen of every pig symmertrically in grid by tattoo. The botulinum toxin A was injected in cutaneous muscle of one side as experimental group, the saline in other side as the control group. Implant a 200ml expander beneath the cutaneous muscle on the bilateral chest and abdomen. The expander was inflated to the same pressure 90mmHg each time. It was inflated twice a week. Compare the basic expanded pressure, the inflated volume of each time, the expansion period, the expanded areas, the retraction rate of flap, as well as the histologic change of experimental group with the control group.
Results: (1) the average expansion period in experimental group was 28±4.5 days, the control group was 42±3.5 days, there was significant difference between two groups(P<0. 01); (2) the inflated volume of each time in experimental group was 26.1±3.5ml, total 8±0.5 times, the control group was 16.7±0.9ml, total 12±0.8 times, there were significant differences(P<0. 01) ; (3) the basic expanded pressure in experimental group was 3.4±0.6mmHg, the control group was 10.1±0.8mmHg, there was significant difference between two groups(P<0. 01); (4) the increased ratio of centre part in experimental group was 69%, the increased ratio of whole area in experimental group was 58%, the increased ratio of centre part in control group was 57%, the increased ratio of whole area was 42%, there were significant differences between two groups(P<0. 01); (5)the instant retraction rate of flap in experimental group was smaller than the control group, not only in width and length, but in area(P<0.01); (6) the retraction of earlier period in experimental group was smaller than the control group(P<0. 05), but there was no difference in midanaphase between two groups(P>0.05); (7) the histologic examination suggested there was no differences in epidermis and derma between two groups, the cutaneous muscle in experimental group showed atrophy, electroscope examination showed A-H bands were dim and Z lines were irregular and curvate, the cutaneous muscle in experimental group showed necrosis 6 weeks later.
ExperimentⅡ
Study on biomechanical characteristics of using botulinum toxin A inforehead expanded flap
Methods: The four guinea pigs were the model of animal studies. Mark the bilateral chest and abdomen of every pig symmertrically in grid by tattoo. The botulinum toxin A was injected in cutaneous muscle of one side as experimental group, the saline in other side as the control group. Implant a 200ml expander beneath the cutaneous muscle on the bilateral chest and abdomen. It was inflated 20ml each time, twice a week. After finished expansion, the speciments were cutted from the expanded flap, resect the capsule. The stress-strain relationship, stress relaxation and creep of these specimens were tested by using the material testing machine Instron4302.
Results: the biomechanics properties in experimental group, such as stress-strain relationship, stress relaxation and creep, were better than the control group.
PartⅡ
Clinic research of using botulinum toxin A in
forehead soft tissue expansion
Methods: In clinic research, the 6 patients were in own control. The forehead was divided into two sides. Botulinum toxin A was injected in one side of forehead muscle and the saline in another side. After implanted the expander, the expansion period, pain and the thickness of flap were observed.
Results: The average expansion period was 52 days; the pain index in experimental side was smaller than the control side; the expanded flap in experimental side was thinner than the control side; there was no side effect of botulinum toxin A and the patients were satisfied with the results.
Conclusions
Using the botulinum toxin A in forehead soft tissue expansion,
1. it can reduce the inflational resistance, accelerate the expansion and shorten the expansion period;
2. it can release the pain of expansion and accelerate the expansion;
3. it can supply the more effective area of expansion;
4. it can decrease the instant and early retraction of expanded flap, which is benefit for the scar of incision;
5. it can improve the the biomechanics properties of forehead expanded flap;
6. it make the forehead expanded flap thinner, which is suitable for facial repair.
第一部分动物实验研究
实验一A型肉毒毒素应用于额部皮肤软组织扩张的动物实验研究
方法:选用6只小型猪作为实验动物,于其两侧胸腹部作网格样文身标记;一侧胸腹部皮肌注射A型肉毒毒素,另一侧注射生理盐水作为对照;两侧皮肌下植入200ml扩张器;扩张器每次注水量以扩张器囊内压达90mmHg为标准,每周注水两次,比较两侧注水前基础囊内压、每次注水量、扩张时间、扩张面积、皮瓣即时及远期回缩,并进行组织学及电镜检测。
结果:
1.实验组平均注水时间为28±4.5天,对照组为42±3.5天,有显著差异(P＜0.01);
2.实验组平均注水8±0.5次,每次注水量为26.1±3.5ml;对照组平均注水12±0.8次,每次注水量为16.7±0.9ml,两组间有显著差异(P＜0.01);
3.实验组平均基础囊内压为3.4±0.6mmHg,对照组为10.1±0.8mmHg,两者有显著差异(P＜0.01);
4.实验组扩张中心面积平均增加69%,整个扩张面积增加58%;对照组扩张中心面积增加57%,整个扩张面积增加42%,有显著性差异(P＜0.01);
5.实验组扩张皮瓣即时回缩率,无论从长度、宽度,还是面积来说,均小于对照组(P＜0.01);
6.皮瓣转移后早期实验组皮瓣回缩小于对照组(P＜0.05),中后期无明显差异(P＞0.05);
7.组织学检测显示两组皮瓣在表皮及真皮形态结构上无差别,实验组皮肌出现萎缩,电镜显示明暗带模糊,Z线排列弯曲、不规则,转移6周后出现肌细胞变性坏死。
实验二A型肉毒毒素注射对额部扩张皮瓣生物力学特性的影响
方法:选用4只小型猪作为实验动物,于其胸腹部作网格样文身标记;一侧皮肌注射A型肉毒毒素,另一侧注射生理盐水作为对照;两侧皮肌下植入200ml扩张器;扩张器每次注水20ml,每周注水两次;注水完成后,切取全层扩张皮瓣,去除包膜,在Instron4302万能材料试验机上对皮瓣试件进行应力—应变、应力松弛和蠕变性能检测。
结果:实验组扩张皮瓣的应力—应变、应力松弛及蠕变性能均优于对照组。
第二部分A型肉毒毒素在额部皮肤软组织扩张中的临床应用研究
方法:临床研究以6例患者进行额部自身对照研究,即平分额部扩张器植入区,一侧额肌注射A型肉毒毒素,另一侧作为对照,测量注水时间,评价注水时的疼痛指标,比较皮瓣厚度,观察临床疗效。
结果:平均注水时间为52天;注水时实验侧疼痛指标小于对照侧;注水过程中实验侧扩张速度及扩张面积大于对照侧;实验侧扩张皮瓣厚度小于对照侧;未出现A型肉毒毒素相关毒副作用;临床效果良好。
结论:
1.应用A型肉毒毒素可以使额部扩张阻力减小,扩张速度加快,扩张时间缩短;
2.应用A型肉毒毒素可以减轻额部扩张器注水时的疼痛,加快扩张速度,减轻患者心理负担;
3.应用A型肉毒毒素可以增加额部软组织扩张的有效扩张面积;
4.应用A型肉毒毒素可以减少额部扩张皮瓣的即时及早期回缩,有利于切口愈合,减少瘢痕形成;
5.应用A型肉毒毒素可以提高额部扩张皮瓣的生物力学性能;
6.应用A型肉毒毒素可以使额部扩张皮瓣变薄,有利于颜面部缺损的修复,可以取得良好的临床效果。
Background and Objective: The forehead expanded flap has been extensively used in therapy of facial trauma, scar, tumor and congenital deformity, because it have obvious advantages such as resembled color, abundant blood supply, and easy to be transferred. The forehead soft tissue expansion has become the best method for nasal reconstruction. However, the forehead anatomy demand the expander is implanted beneath the forehead muscle. So, the forehead soft tissue expansion is different from other region, as following: both skin and forehead muscle limit the expansion, prolong the therapy time; the patient feel headache and nausea while inflating, which slow the velocity of inflation; the forehead expanded flap, including the forehead muscle, is thick for the face; the forehead expanded flap tend to retraction. Therefore, we used the botulinum toxin A to make the forehead muscle paralysis and atrophy. The goal of our animal studies and clinical research is to investigate if the botulinum toxin A may reduce the expansion period, eliminate the pain and thin the expanded flap.
PartⅠAnimal ExperimentsExperimentⅠ
Animal experiment of using botulinum toxin A inforehead soft tissue expansion
Methods: The six guinea pigs were the model of animal studies. Mark the bilateral chest and abdomen of every pig symmertrically in grid by tattoo. The botulinum toxin A was injected in cutaneous muscle of one side as experimental group, the saline in other side as the control group. Implant a 200ml expander beneath the cutaneous muscle on the bilateral chest and abdomen. The expander was inflated to the same pressure 90mmHg each time. It was inflated twice a week. Compare the basic expanded pressure, the inflated volume of each time, the expansion period, the expanded areas, the retraction rate of flap, as well as the histologic change of experimental group with the control group.
Results: (1) the average expansion period in experimental group was 28±4.5 days, the control group was 42±3.5 days, there was significant difference between two groups(P<0. 01); (2) the inflated volume of each time in experimental group was 26.1±3.5ml, total 8±0.5 times, the control group was 16.7±0.9ml, total 12±0.8 times, there were significant differences(P<0. 01) ; (3) the basic expanded pressure in experimental group was 3.4±0.6mmHg, the control group was 10.1±0.8mmHg, there was significant difference between two groups(P<0. 01); (4) the increased ratio of centre part in experimental group was 69%, the increased ratio of whole area in experimental group was 58%, the increased ratio of centre part in control group was 57%, the increased ratio of whole area was 42%, there were significant differences between two groups(P<0. 01); (5)the instant retraction rate of flap in experimental group was smaller than the control group, not only in width and length, but in area(P<0.01); (6) the retraction of earlier period in experimental group was smaller than the control group(P<0. 05), but there was no difference in midanaphase between two groups(P>0.05); (7) the histologic examination suggested there was no differences in epidermis and derma between two groups, the cutaneous muscle in experimental group showed atrophy, electroscope examination showed A-H bands were dim and Z lines were irregular and curvate, the cutaneous muscle in experimental group showed necrosis 6 weeks later.
ExperimentⅡ
Study on biomechanical characteristics of using botulinum toxin A inforehead expanded flap
Methods: The four guinea pigs were the model of animal studies. Mark the bilateral chest and abdomen of every pig symmertrically in grid by tattoo. The botulinum toxin A was injected in cutaneous muscle of one side as experimental group, the saline in other side as the control group. Implant a 200ml expander beneath the cutaneous muscle on the bilateral chest and abdomen. It was inflated 20ml each time, twice a week. After finished expansion, the speciments were cutted from the expanded flap, resect the capsule. The stress-strain relationship, stress relaxation and creep of these specimens were tested by using the material testing machine Instron4302.
Results: the biomechanics properties in experimental group, such as stress-strain relationship, stress relaxation and creep, were better than the control group.
PartⅡ
Clinic research of using botulinum toxin A in
forehead soft tissue expansion
Methods: In clinic research, the 6 patients were in own control. The forehead was divided into two sides. Botulinum toxin A was injected in one side of forehead muscle and the saline in another side. After implanted the expander, the expansion period, pain and the thickness of flap were observed.
Results: The average expansion period was 52 days; the pain index in experimental side was smaller than the control side; the expanded flap in experimental side was thinner than the control side; there was no side effect of botulinum toxin A and the patients were satisfied with the results.
Conclusions
Using the botulinum toxin A in forehead soft tissue expansion,
1. it can reduce the inflational resistance, accelerate the expansion and shorten the expansion period;
2. it can release the pain of expansion and accelerate the expansion;
3. it can supply the more effective area of expansion;
4. it can decrease the instant and early retraction of expanded flap, which is benefit for the scar of incision;
5. it can improve the the biomechanics properties of forehead expanded flap;
6. it make the forehead expanded flap thinner, which is suitable for facial repair.
引文
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