消痹灵注射液对退行性骨关节炎的防治作用及其机理研究
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摘要
退行性骨关节炎(Degenerative Osteoarthritis，OA)是我国四大老年病之一，是一种严重影响病人生活质量和社会生产力的慢性病。随着我国人口的老龄化进程，OA的患病率高达总人口的8．3％。该病是以关节软骨退变为核心，累及骨质，并包括滑膜、关节囊及关节囊外其它结构的不同程度的炎性病变，对其研究已涉及细胞水平及分子水平。
目的：研究消痹灵注射液对骨性关节炎的治疗作用。方法：健康成年日本大耳白兔50只，随机分为消痹灵治疗组(A组)、透明质酸钠组(B组)、生理盐水组(C组)、模型组(D组)、正常组(E组)，每组10只。同等条件下饲养一周后，除E组外，其余各组均采用改良的Hulth造模方法制作实验性KOA模型。将3％戊巴比妥钠按30mg／kg用量进行耳缘静脉麻醉，麻醉成功后，将兔仰卧捆绑于手术台上，取左侧后肢膝关节内侧纵切口，长约4cm，探查关节腔无原发病变，切断内侧副韧带及前交叉韧带，完整切除内侧半月板，逐层缝合伤口，无菌敷料及绷带包扎固定。术后每天肌注青霉素20万u预防感染，抗炎治疗3天，术后模型兔采用一笼一兔喂养，每天强迫动物活动30分钟。于造模一周后开始给模型动物关节腔内注射药物，A组注射消痹灵注射液0．3ml／只，B组注射透明质酸注射液0．3ml／只，C组注射生理盐水0．3ml／只，每周一次，连续给药8周。D组动物不给药，只模拟捉拿。研究指标：于治疗8周后，每组随机捉取8只家兔，进行关节滑液IL-1、TNF-α含量的检测，同时进行标本观察及观察滑膜和软骨的光镜下病理变化。用免疫组化方法检测软骨中的MMP-1、TIMP-1的表达以及运用反转录聚合酶链式反应(RT-PCR)检测关节软骨组织中的MMP-1、TIMP-1的mRNA表达。结果：消痹灵注射液治疗组动物骨性关节炎病理组织学及血液流变学病理改变明显减轻，可见软骨破坏减轻，滑膜炎症明显抑制，Mankin’s评分有明显的改善(P＜0．01)；膝关节滑液IL-1浓度和TNF-α含量降低(P＜0．05)，关节软骨中MMP-1表达明显减弱，TIMP-1的表达明显增强。结论：消痹灵注射液关节腔内注射能抑制滑膜炎症，减少关节内有害细胞因子浓度，缓解软骨破坏的进程。
Degenerative Osteoarthritis (OA) is the one of the four elderlypatients in China. It effects seriously on work and live ofPeople. Along with our country population aging, OA prevalence ratereaches as high as the total population 8.3%.Should sickness bedraws back by the articular cartilage becomes the core, Implicatesthe ossein, And inctudes outside the synovial membrane ligamentumcapoulare and the ligamentum capoulare the other structure varyingdegree inflammatory affection. Has involved the cell level and themolecular level to its research.
[Objective] Study on Xiao-Bi-Ling injection on the treatment of OA.
[Methods] Health adult Japan big ear white rabbit 50.0A modelanimals were randomly divided into 5 groups:group A, group B,group C, group D and group E. Animals in group A received XiaoBiLinginjection and animals in group B received Sodium hyaluronate (HA),groupC was sterilized normal saline intramuscularly, groupD wascontrol and received nothing and another group(groupE)was used fornomal control. Each group of 10.Under the same level conditionraises one week later, Besides E group, The other groups are improvedmethods of production model Hulth experimental of OA. With 3%pentobarbitol sodium 30mg/kg after rabbit ear reason intravenousanesthesia, lies supine on the bundle the rabbit and the surgerytable, takes the left knee inside vertical margin, long about 4cm,investigation ticulare not primary pathological change, cut-offinside ligamentum accessorium and first overlapping ligament,complete excision inside meniscus, the cascade sutures the wound,the sterilized dressing and the bandage wrap are fixed. After thetechnique, the anti-SARS treats for 3 days, minute cage raising, every day forces the animal to move 30 minutes. After making themodel one week later starts injects the medicine, A group injectsXiao-Bi-Ling injection 0.3ml, B group injects the Sodiumhyaluronate 0.3ml, C group injects physiological saline 0.3ml,once a week, gives the medicine 8 weeks continuously. D group ofanimal does not give the medicine, the simulation apprehends.Research target: After treatment 8 weeks later, each group takes8 rabbits stochastically, Examination the joint synovial fluid IL-1and TNF-αcontent, Simultaneously carries on the specimenobservation and under the synovial membrane cartilage's lightmicroscope the pathological change, Immunohistochemical detectionof cartilage MMP-1, TIMP-1 expression, as well as the use of PCRto detect MMP-1, TIMP-1 expression of mRNA.
[Results] Xiao-Bi-ling treated group Injection osteoarthritisanimal histology and hemorrheology significantly reduce thepathological changes, obviously the cartilage destroys reduces,Synovitis disease inhibit, The Mankin'S grading has the distinctimprovemen(P＜0.01); knee joint synovial fluid, IL-1 and TNF-αconcentration decreased (P＜0.05), Articular cartilage in the MMP-1expression was significantly reduced, TIMP-1 expression wassignificantly enhanced, Electron microscope, synovial A, B cellsreturn to normal functional status.
[Conclusion] Xiao-Bi-ling Injection intra-articular injection cansuppress the disease Synovitis, Reduces in the joint harmful cellfactor Quantity, alleviates to cartilage's destruction.
目的：研究消痹灵注射液对骨性关节炎的治疗作用。方法：健康成年日本大耳白兔50只，随机分为消痹灵治疗组(A组)、透明质酸钠组(B组)、生理盐水组(C组)、模型组(D组)、正常组(E组)，每组10只。同等条件下饲养一周后，除E组外，其余各组均采用改良的Hulth造模方法制作实验性KOA模型。将3％戊巴比妥钠按30mg／kg用量进行耳缘静脉麻醉，麻醉成功后，将兔仰卧捆绑于手术台上，取左侧后肢膝关节内侧纵切口，长约4cm，探查关节腔无原发病变，切断内侧副韧带及前交叉韧带，完整切除内侧半月板，逐层缝合伤口，无菌敷料及绷带包扎固定。术后每天肌注青霉素20万u预防感染，抗炎治疗3天，术后模型兔采用一笼一兔喂养，每天强迫动物活动30分钟。于造模一周后开始给模型动物关节腔内注射药物，A组注射消痹灵注射液0．3ml／只，B组注射透明质酸注射液0．3ml／只，C组注射生理盐水0．3ml／只，每周一次，连续给药8周。D组动物不给药，只模拟捉拿。研究指标：于治疗8周后，每组随机捉取8只家兔，进行关节滑液IL-1、TNF-α含量的检测，同时进行标本观察及观察滑膜和软骨的光镜下病理变化。用免疫组化方法检测软骨中的MMP-1、TIMP-1的表达以及运用反转录聚合酶链式反应(RT-PCR)检测关节软骨组织中的MMP-1、TIMP-1的mRNA表达。结果：消痹灵注射液治疗组动物骨性关节炎病理组织学及血液流变学病理改变明显减轻，可见软骨破坏减轻，滑膜炎症明显抑制，Mankin’s评分有明显的改善(P＜0．01)；膝关节滑液IL-1浓度和TNF-α含量降低(P＜0．05)，关节软骨中MMP-1表达明显减弱，TIMP-1的表达明显增强。结论：消痹灵注射液关节腔内注射能抑制滑膜炎症，减少关节内有害细胞因子浓度，缓解软骨破坏的进程。
Degenerative Osteoarthritis (OA) is the one of the four elderlypatients in China. It effects seriously on work and live ofPeople. Along with our country population aging, OA prevalence ratereaches as high as the total population 8.3%.Should sickness bedraws back by the articular cartilage becomes the core, Implicatesthe ossein, And inctudes outside the synovial membrane ligamentumcapoulare and the ligamentum capoulare the other structure varyingdegree inflammatory affection. Has involved the cell level and themolecular level to its research.
[Objective] Study on Xiao-Bi-Ling injection on the treatment of OA.
[Methods] Health adult Japan big ear white rabbit 50.0A modelanimals were randomly divided into 5 groups:group A, group B,group C, group D and group E. Animals in group A received XiaoBiLinginjection and animals in group B received Sodium hyaluronate (HA),groupC was sterilized normal saline intramuscularly, groupD wascontrol and received nothing and another group(groupE)was used fornomal control. Each group of 10.Under the same level conditionraises one week later, Besides E group, The other groups are improvedmethods of production model Hulth experimental of OA. With 3%pentobarbitol sodium 30mg/kg after rabbit ear reason intravenousanesthesia, lies supine on the bundle the rabbit and the surgerytable, takes the left knee inside vertical margin, long about 4cm,investigation ticulare not primary pathological change, cut-offinside ligamentum accessorium and first overlapping ligament,complete excision inside meniscus, the cascade sutures the wound,the sterilized dressing and the bandage wrap are fixed. After thetechnique, the anti-SARS treats for 3 days, minute cage raising, every day forces the animal to move 30 minutes. After making themodel one week later starts injects the medicine, A group injectsXiao-Bi-Ling injection 0.3ml, B group injects the Sodiumhyaluronate 0.3ml, C group injects physiological saline 0.3ml,once a week, gives the medicine 8 weeks continuously. D group ofanimal does not give the medicine, the simulation apprehends.Research target: After treatment 8 weeks later, each group takes8 rabbits stochastically, Examination the joint synovial fluid IL-1and TNF-αcontent, Simultaneously carries on the specimenobservation and under the synovial membrane cartilage's lightmicroscope the pathological change, Immunohistochemical detectionof cartilage MMP-1, TIMP-1 expression, as well as the use of PCRto detect MMP-1, TIMP-1 expression of mRNA.
[Results] Xiao-Bi-ling treated group Injection osteoarthritisanimal histology and hemorrheology significantly reduce thepathological changes, obviously the cartilage destroys reduces,Synovitis disease inhibit, The Mankin'S grading has the distinctimprovemen(P＜0.01); knee joint synovial fluid, IL-1 and TNF-αconcentration decreased (P＜0.05), Articular cartilage in the MMP-1expression was significantly reduced, TIMP-1 expression wassignificantly enhanced, Electron microscope, synovial A, B cellsreturn to normal functional status.
[Conclusion] Xiao-Bi-ling Injection intra-articular injection cansuppress the disease Synovitis, Reduces in the joint harmful cellfactor Quantity, alleviates to cartilage's destruction.
引文
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