度冷丁溶液对成年大鼠臀肌挛缩症影响的实验研究
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摘要
目的:探讨肌肉注射度冷丁溶液与臀肌挛缩症的关系。臀肌挛缩症(Gluteal muscle contracture,GMC),又称臀肌纤维化,是由多种原因引起的臀肌及筋膜纤维挛缩变性,导致髋关节功能受限,表现出特有的步态、体征、髋关节功能障碍,特别是髋内收困难和髋外展畸形的临床综合征。临床上以注射性臀肌挛缩症最为多见。多发于儿童期,注射的药物多为以苯甲醇为溶剂的青霉素,近年来随着苯甲醇溶剂对GMC影响的流行病学调查发现,临床上已基本上摈弃了苯甲醇溶剂,儿童GMC发病数量逐步减少,但成人GMC发病数量逐步增多。以肌肉注射度冷丁的患者增长最为迅速,多自成年后开始注射度冷丁。本实验目的是研究肌肉注射度冷丁对GMC的影响,观察停止注射度冷丁后GMC的恢复情况。本实验对3组成年Wistar大鼠分别进行肌肉注射苯甲醇青霉素溶液作为阳性对照组、度冷丁溶液作为实验组和生理盐水青霉素溶液作为阴性对照组,观察各组大鼠步态变化情况、测量肌肉等张牵拉长度与原长比值的变化、观察大体标本及病理变化。明确肌肉注射度冷丁溶液与GMC的关系,为临床防治度冷丁导致的GMC提供参考。
     方法:选取体重为180~220g Wistar大鼠80只,随机分为3组:1大组为阳性对照组20只,注射苯甲醇青霉素溶液,分为1.1组、1.2组、1.3组、1.4组4小组,分别在注射2周、4周、6周、8周后处死;2大组为阴性对照组20只,注射生理盐水青霉素溶液,分为2.1组、2.2组、2.3组、2.4组4小组,分别在注射2周、4周、6周、8周后处死;3大组为实验组40只,分为8小组其中3.1a组、3.2a组、3.3a组、3.4a组分别进行2周、4周、6周、8周度冷丁注射后处死;3.1b组、3.2b组、3.3b组、3.4b组在进行2周、4周、6周、8周度冷丁注射后停止注射,饲养2周以后再处死。为避免因注射导致的疼痛引起的步态变化影响观察结果,所有大鼠在每次注射完2小时后再观察步态变化,并作记录。大鼠处死后取臀部注射部位肌肉,进行大体观察肌肉色泽、弹性、肌张力,取肌束测量等张牵拉长度,与肌束原长相比,求出比值,将测试后的标本用福尔马林固定液中固定,用于制作组织切片,染色后光镜下观察肌肉变化情况。所有数据运用SPSS软件进行统计学分析。
     结果:1步态观察:苯甲醇青霉素组在注射3周后部分大鼠步态出现异常行走跛行,6周后所有大鼠出现了行走跛行,8周后大鼠跛行十分严重;生理盐水青霉素组大鼠在第7周时有一只大鼠有步态异常表现,行走稍跛行,其余大鼠注射期间未发现步态异常;实验组在注射4周后少数大鼠出现行走跛行,6周后大部分大鼠步态出现异常,停止注射后可以恢复正常,8周后大鼠步态异常更为明显,停止注射后步态异常未见明显恢复。
     2肌肉等张牵拉后长度与原长比值的统计分析:苯甲醇青霉素组的4小组内组间比较均有统计学差异;生理盐水青霉素组的4小组内组间比较均无统计学差异;实验组内3.4a组与3.4a组之间无统计学差异,3.1a组、3.1b组、3.2a组、3.2b组、3.3b组间比较均无统计学差异。
     3大体标本观察:1.1组、2大组、3.1a组、3.1b组、3.2b组可见肌肉颜色红润,未见挛缩带,肌肉弹性好;1.2组、3.2a组、3.3b组大鼠臀肌可见稍苍白,弹性减弱,少数发现纤维挛缩束带。1.3组、1.4组、3.3a组、3.4a组、3.4b组大鼠臀肌可见部分纤维挛缩束带,为1~2mm,累及臀大肌全层,色泽苍白,无弹性,呈腱样组织,严重者伴有臀肌整个肌群的挛缩,滑液增多。
     4光镜观察:2.1组、2.2组、2.3组、3.1a组、3.1b组、3.2b组肌纤维排列整齐,核大小适中,染色质着色均匀;1.1组、2.4组、3.2a组、3.3b组臀肌细胞胞体稍肿胀,染色质着色适中,肌纤维间隙增宽,可见中性粒细胞及淋巴细胞浸润;1.2组、3.3a组、3.4a组、3.4b组可见肌纤维排列紊乱,胞浆着色较淡,核固缩,肌纤维间间隙明显增宽,中性粒细胞及淋巴细胞浸润,肌纤维间及肌束间可见胶原纤维;1.4组肌纤维排列紊乱卷曲,肌细胞明显萎缩,胞核增多并延肌纤维呈串珠样排列,肌纤维间隙明显增高,较多中性粒细胞及淋巴细胞浸润,大量胶原纤维增生,纤维化区域可见大片致密胶原纤维结缔组织,粗大胶原束内可见一些细长梭形的纤维细胞,与胶原纤维平行走向,同肌腱结构相似。
     结论:1大鼠臀肌注射苯甲醇青霉素溶液可以导致大鼠GMC,注射1月后大部分大鼠出现GMC症状,注射6周后GMC症状加重,8周后GMC症状十分严重;2大鼠臀肌注射度冷丁溶液可以导致大鼠GMC,注射6周后大部分大鼠出现GMC症状,8周后少数大鼠GMC症状十分严重;3在大鼠臀肌注射度冷丁6周后停止注射,大鼠臀肌可以恢复正常。在大鼠臀肌注射度冷丁8周后,大鼠臀肌不可恢复。4频繁肌肉注射生理盐水青霉素溶液是GMC的一个影响因素。5成年大鼠臀肌注射苯甲醇青霉素溶液对大鼠GMC的影响大于度冷丁溶液。
Objective:Investigate relations of intramuscular injection meperidine hydrochloride solution and gluteus contracture disease. It was by manifold cause creative gluteus cum fasciae fibre contracture denaturalization,result in coxae function restriction, appear to be of proper gait, sign, coxae disfunction, especially coxae adduction difficulty and coxae abduction monstrous clinic syndrome that gluteus contracture disease gluteal muscle contracture, GMC again weigh fibrosis of gluteal muscle,gluteus contracture disease. Clinically with injection gender gluteus contracture disease most for much saw. The medicament much for with benzyl alcohol for solvent penicillin, in recent years in company with versus benzy alcohol solvent versus GMC influencing epidemiological survey discover, clinically hexy these go to ostracism know clearly benzyl alcohol solven, children GMC attack quantity scale-down, therefor adult GMC attack quantity gradually manifold to of the even much higher to childhood, injection meperidine hydrochloride with intramuscular injection meperidine hydrochloride sufferer rose most for promptitude, furthermore much automatic thickness gauge manhood queen. The objective of this experiment is to study the impact of intramuscular meperidine for the GMC. GMC pethidine injection after observing the cease recovery. The three components of the experiment, rats were intramuscular penicillin benzyl alcohol solution as a positive control group. Meperidine as the experimental group and the saline solution penicillin solution as a negative control group. Gait changes observed in rats, measuring the length and stretch muscle Zhang original length ratio, and pathological changes observed specimen. Intramuscular meperidine clear solution and the GMC, the GMC lead for clinical reference meperidine.
     Methods: 180-220 g body weight of 80 Wistar rats were randomly divided into 3 groups: one large group as a positive control group of 20, penicillin injection of benzyl alcohol solution, divided into 110 groups, 120 groups and 130 groups 1.4 Section 4 groups were injected in two weeks, four weeks, six weeks, eight weeks after the death of 2 large group of 20 negative control group. penicillin injection of saline solution into 210 groups, 2.2, 2.3 Section 2.4 Section 4 team Injection in two weeks, four weeks, six weeks, eight weeks after the death of 3 experimental groups in 40. 3.1a group which consists of eight groups stipulate Section 3.3a Section 3.4a group for two weeks, four weeks, 6 weeks, 8 weeks after the death; 3.1b pethidine injection group parentheses group nearest group 3.4b group during two weeks, four weeks, six weeks, eight weeks after the injection of pethidine injection, 2 weeks later executed. To avoid the pain caused by the injection gait change observations, All rats in the 2 hours after each injection End observed gait changes, and for the record. The rats were sacrificed after admission buttock muscle injection for the whole muscle color, flexibility, muscle tone, Zhang stretch fiber length measurement admission, the original band with a long, calculated ratios, After the test specimens were fixed with formalin fixative for the production of tissues After changes in muscle were observed under light microscope. All data were analyzed by SPSS.
     Results: 1 Gait observe:benzyl alcohol penicillin group gait in rats injected some three weeks after walking gait abnormalities claudication, After six weeks, all the rats were running a limp, eight weeks after rats claudication is very serious; saline group in the first seven weeks of penicillin when a rat is abnormal gait, walking slightly lame, During the rest of the rat found abnormal gait; 4 weeks after injection of the experimental group emerged a few rats running claudication. After six weeks, rats most unusual gait, can return to normal after they stop the injection. After 8 weeks significantly more rats abnormal gait, abnormal gait stop no significant recovery after injection.
     2 Muscle wait sheet pull spin and ortho length ratio tatistical analysis: benzyl alcohol group of four penicillin group were statistically significant difference between the two groups; NS Group 4 penicillin group no statistically significant difference between the two groups; 3.4a group and the experimental group with no significant difference between 3.4a, 3.1a group 3.1b group, Section 3.2a, 3.2b group, no statistically significant difference between the two groups was monitored.
     3 Gross specimen observe: 1.1 specimen observation group, the second largest group, 3.1a group 3.1b group, ruddy color shown muscle group can be seen, with no contracture, good muscle flexibility in 1.2 group stipulate group gluteal muscle monitored rats shows little pale and weakened flexibility, a few fibers found contracture constrictions. Section 1.3, Section 1.4, 3.3a Section 3.4a group 3.4b rats shows some gluteal muscle fiber contraction constrictions of 1-2 mm, 16.4 gluteus maximus layer of pale color, inflexible, the tendon tissue was seriously accompanied by the entire gluteal muscle contracture, synovial fluid increased.
     4 Light microscope observation: 2.1 light microscopy, Section 2.2, Section 2.3, Section 3.1a, 3.1b group, Group neat muscle fibers shown that nuclear size, color uniform chromatin ;1.1 Section 240 groups, Section 3.2a, 3.3b group slightly swollen body gluteal muscle cells, chromatin coloring moderate, the gap widened muscle fibers. Neutrophils and lymphocytes can be seen in 1.2Section , 3.3a Section, 3.4a group and 3.4b group shows muscle fiber disorder, was stained more lightly, nuclear condensation, significantly widened the gap between the muscle fibers. Neutrophil and lymphocyte infiltration between the muscle fibers and collagen fibers can be seen between the band; Section 1.4 curly fibers disorder, muscle cells shrink, and extended nucleus increased muscle fibers were arranged beaded, Gap muscle fibers increased significantly more neutrophils and lymphocytes, a lot of collagen fibers hyperplasia, Regional shows fibrosis large dense connective tissue collagen fibers. Seen in some coarse collagen fibers slender spindle cells, and collagen fibers in parallel to the same tendon structure similar.
     Conclusion : 1 Gluteal muscle in rats injected with penicillin could lead to rat GMC benzyl alcohol. GMC injection in January after most of the rats had symptoms six weeks after injection GMC syptoms. GMC very serious symptoms after 8 weeks, 2 Rats gluteal injection solution could lead to rat GMC meperidine. Most of the rats had six weeks after injection GMC symptoms after eight weeks of very few serious symptoms in rats GMC; 3 Gluteal muscle in rats 6 weeks after the injection of pethidine injection, the rats gluteal muscle can return to normal. Eight weeks after injection of pethidine gluteal muscle in rats, rats gluteal muscle could not be restored. 4 Frequent intramuscular penicillin saline solution is a significant factor GMC. 5 Adult rats gluteal injection of benzyl alcohol solution to the rat GMC outweighed the effect of penicillin meperidine solution.
引文
1 Valderrama JAF de, A cause of limiter flexion and adduction of the hip in children [J]. J Bone Joint surge Br. 1970,52:179
    2 马承宣日,房论光,刘贵林,等.注射性臀大肌挛缩症[J] .中华外科杂志,1987,16 (6):987~990
    3 王斌,贺西京,巫永军,等.臀肌挛缩症的前瞻性调查及病因分析[J].中国骨伤,2003, 16 (3):157~158
    4 杜靖远,沈霖,杨家玉,等.儿童臀肌挛缩症的红细胞免疫功能研究[J].中华小儿外科杂志,1991, 12(2):112
    5 周素华,彭明惺,刘利君,等.儿童注射性臀肌挛缩症与易感因素的探讨[J].中华小儿外科杂志,1992,13 (1):30~31
    6 Richhard J, Bleicher, Harold FS, et al. Bilateral Gluteal Compartment Syndrome [J]. The Jounal of Trauma: Injury Infection and Critical care , 1997, 42 (1) : 118~122
    7 Sheridan GW, Matse FA, Krugmire RB. Further investigations on the thophysiology of the compartment syophysiology of the compartment sydrome [J]. Clin Orthop, 1997, 123, 60B: 252~255
    8 黄耀添,李建文,雷伟,等. 臀肌挛缩症的病因、类型及治疗[J]. 中华骨科杂志,1999,19(2):106~108
    9 李群伟,景学安,吴多文,等.青霉素溶液对大鼠臀肌纤维化影响的实验观察[J]. 泰山医学院学报,2002, 23 (4):334~336
    10 Jose A, Fernandez DE, valderrama, Ra 平国兴,黄建凯,丘德赞,等.重症臀肌挛缩的诊断与手术治疗[J].中华骨科杂志,2003,23 9(7):418~422
    11 Fael Esteve DE Miguel. Fibosis of Limeted Flexion and Adduction of the hip in children[J].Clinical Orthopaedics and Related Research, 1981, 156, 67~78
    12 马承宣,许瑞红,房论光,等.注射性臀大肌挛缩症的临床病理变化[J]. 中华小儿外科杂志,1990,11 (1):39
    13 余希临,刘波,沈先涛,等.儿童臀肌挛缩评分标准的临应用[J].中国矫形外科杂志,1999,6 (4):302~303
    14 蔡金华,甘兰丰,郑鹤林,等. 臀肌挛缩症的一种新X行征象—髂骨致密线[J].中华放射性杂志,2003,37 (2):144~146
    15 王龙胜,张红亮.臀肌挛缩症的CT诊断[J].中国医学影像杂志,2001,11 (3):215~216
    16 文达辉,梁寒洁,柯楚群,等.臀肌筋膜挛缩症的超声诊断及临床分型对比研究[J].中国医学影像技术,2000,16(1):66~67
    17 赵涛,尤玉华,孙晶,等.臀肌挛缩症的MRI应用价值[J].骨骼肌肉系统放射学,2003,37 (9):823~826
    18 秦泗河,彭爱民,陈建文,等.重度臀肌挛缩症继发骨与关节畸形[J].中国矫形外科杂志,2003,11 (15):1078~1079
    19 黄枢,田佩洲,马金鼎,等.臀肌挛缩症的针法微型手术治疗[J].中华矫形外科杂志,2004,12 (9):713~714
    20 张文涛,王岩,王志刚,等.关节镜下软组织松解治疗臀肌挛缩症[J].中国临床康复,2002,6 (12):1758~1759
    21 刘玉杰,张文涛,李众利,等.射频气化技术在关节镜手术的临床应用[J].解放军医学杂志,2002,27 (12):1117~1118
    22 赵 涛,孙 晶,尤玉华等. 臀肌挛缩症的MRI应用价值 中华放射学杂志,2003,37 (9):823
    23 郑稼,罗建平,赵炬才,等.臀肌起点下移治疗臀肌挛缩症[J].中华骨科杂志,1999,19 (8):480
    24 顾洁夫.儿童臀肌挛缩症的诊治及病因学研究[J].中华小儿外科杂志,1989,10 (6):353
    25 兰志辉,李海江,韩巨才,等.臀肌挛缩症二家系六例[J].中华医学遗传学杂志,1994,11:58
    26 史占军,何飞姣.臀肌注射与臀肌挛缩的流行病学研究[J].中华预防医学杂志,1995,29:125
    27 沈品泉,汪启筹.臀肌挛缩诊治进展[J].中国矫形外科杂志,1999,6:229~230
    28 李洪,钟生才,赵希唐,等.儿童臀肌、肌筋膜挛缩症[J].中华骨科杂志,1996,16:320
    1 Valderrama JAF de. A cause of limiter flexion and adduction of the hip in children [J]. J Bone Joint surge Br. 1970, 52:179
    2 马承宣, 房论光, 刘贵林,等. 注射性臀大肌挛缩症[J]. 中华外科杂志, 1987, 16(6): 987~990
    3 郑稼,罗建平,赵炬才,等.臀肌起点下移治疗臀肌挛缩症[J].中华骨科杂志,1999,19(8):480
    4 顾洁夫.儿童臀肌挛缩症的诊治及病因学研究[J].中华小儿外科杂志,1989,10(6):353
    5 黄耀添,李建文,雷伟,等.臀肌挛缩症的病因、类型及治疗[J].中华骨科杂志,1999,19(2):106~108
    6 Richhard J,Bleicher,Harold FS,et al.Bilateral Gluteal Compartment Synd-rome[J].The Jounal of Trauma:Injury Infection and Critical care , 1997,42(1):118~122
    7 兰志辉,李海江,韩巨才,等.臀肌挛缩症二家系六例[J].中华医学遗传学杂志,1994,11:58
    8 Sheridan GW,Matsen FA,Krugmire RB.Further investigations on the th-ophysiology of the compartment sy-ophysiology of the compartment sy-drome [J].Clin Orthop,1997,123,60B:252~255
    9 Fael Esteve DE Miguel.Fibosis of Limeted Flexion and Adduction of the hip in children[J].Clinical Orthopaedics and Related Research,1981,156,67~78
    10 史占军,何飞姣.臀肌注射与臀肌挛缩的流行病学研究[J].中华预防医学杂志,1995,29:125
    11 王斌,贺西京,巫永军,等.臀肌挛缩症的前瞻性调查及病因分析[J].中国骨伤,2003,16(3):157~158
    12 王龙胜,张红亮.臀肌挛缩症的CT诊断[J].中国医学影像杂志,2001,11(3):215~216
    13 蔡金华,甘兰丰,郑鹤林,等.臀肌挛缩症的一种新X行征象—髂骨致密线[J].中华放射性杂志,2003,37(2):144~146
    14 赵 涛,孙 晶,尤玉华等 臀肌挛缩症的MRI应用价值 中华放射学杂志,2003,37(9):823
    15 文达辉,梁寒洁,柯楚群,等.臀肌筋膜挛缩症的超声诊断及临床分型对比研究[J].中国医学影像技术,2000,16(1):66~67
    16 JoseA.Fernandez DE valderrama,Ra 平国兴,黄建凯,丘德赞,等.重症臀肌挛缩的诊断与手术治疗[J].中华骨科杂志,2003,23(7):418~422
    17 黄枢,田佩洲,马金鼎,等.臀肌挛缩症的针法微型手术治疗[J].中华矫形外科杂志,2004,12(9):713~714
    18 刘玉杰,张文涛,李众利,等.射频气化技术在关节镜手术的临床应用[J].解放军医学杂志,2002,27(12):1117~1118
    19 杜靖远,沈霖,杨家玉,等.儿童臀肌挛缩症的红细胞免疫功能研究[J].中华小儿外科杂志,1991,12(2):112
    20 周素华,彭明惺,刘利君,等.儿童注射性臀肌挛缩症与易感因素的探讨[J].中华小儿外科杂志,1992,13(1):30~31
    21 李群伟,景学安,吴多文,等.青霉素溶液对大鼠臀肌纤维化影响的实验观察[J].泰山医学院学报,2002,23(4):334~336
    22 马承宣,许瑞红,房论光,等.注射性臀大肌挛缩症的临床病理变化[J].中华小儿外科杂志,1990,11(1):39
    23 余希临,刘波,沈先涛,等.儿童臀肌挛缩评分标准的临应用[J].中国矫形外科杂志,1999,6(4):302~303
    24 秦泗河,彭爱民,陈建文,等.重度臀肌挛缩症继发骨与关节畸形[J].中国矫形外科杂志,2003,11(15):1078~1079
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