CAJ | 학술논문

背景：透骨消痛胶囊是治疗骨性关节炎的临床验方，作用机制尚未完全阐明。尿激酶型纤溶酶原激活系统参与关节软骨的细胞外基质降解及关节滑膜增生，在骨性关节炎的病理过程中起着重要作用。目的：观察透骨消痛胶囊对膝骨性关节炎模型大鼠软骨中尿激酶型纤溶酶原激活系统的影响。方法：SD大鼠144只，随机取120只采用关节腔注射木瓜蛋白酶复制大鼠膝骨性关节炎模型，并随机分为模型组、壮骨关节丸组[1.2 g/(kg?d)]、透骨消痛胶囊低剂量组[0.092 g/(kg?d)]、透骨消痛胶囊中剂量组[0.184 g/(kg?d)]和透骨消痛胶囊高剂量组[0.368 g/(kg?d)]，每组24只，每2周为1个疗程，中间休息2 d，共4个疗程。另取24只正常大鼠为空白组。每2个疗程后，处死一批实验动物，苏木精-伊红染色观察软骨组织病理改变；免疫组织化学反应观察尿激酶型纤溶酶原激活剂、尿激酶型纤溶酶原激活剂受体、纤溶酶原激活物抑制因子阳性表达情况；Western blot检测尿激酶型纤溶酶原激活剂、尿激酶型纤溶酶原激活剂受体、纤溶酶原激活物抑制因子蛋白表达情况。结果与结论：透骨消痛胶囊组和壮骨关节丸组的骨性关节炎大鼠关节软骨 Mankin’s 评分较模型组明显降低(P <0.01)，具有时间依赖；免疫组织化学反应显示，透骨消痛胶囊组和壮骨关节丸组尿激酶型纤溶酶原激活剂、尿激酶型纤溶酶原激活剂受体的阳性率明显降低，而纤溶酶原激活物抑制因子明显升高，具有时间依赖。Western blot检测结果与免疫组织化学具有相同的趋势。提示透骨消痛胶囊可能通过调控尿激酶型纤溶酶原激活剂系统对骨性关节炎发挥防治作用。
배경：투골소통효낭시치료골성관절염적림상험방，작용궤제상미완전천명。뇨격매형섬용매원격활계통삼여관절연골적세포외기질강해급관절활막증생，재골성관절염적병리과정중기착중요작용。목적：관찰투골소통효낭대슬골성관절염모형대서연골중뇨격매형섬용매원격활계통적영향。방법：SD대서144지，수궤취120지채용관절강주사목과단백매복제대서슬골성관절염모형，병수궤분위모형조、장골관절환조[1.2 g/(kg?d)]、투골소통효낭저제량조[0.092 g/(kg?d)]、투골소통효낭중제량조[0.184 g/(kg?d)]화투골소통효낭고제량조[0.368 g/(kg?d)]，매조24지，매2주위1개료정，중간휴식2 d，공4개료정。령취24지정상대서위공백조。매2개료정후，처사일비실험동물，소목정-이홍염색관찰연골조직병리개변；면역조직화학반응관찰뇨격매형섬용매원격활제、뇨격매형섬용매원격활제수체、섬용매원격활물억제인자양성표체정황；Western blot검측뇨격매형섬용매원격활제、뇨격매형섬용매원격활제수체、섬용매원격활물억제인자단백표체정황。결과여결론：투골소통효낭조화장골관절환조적골성관절염대서관절연골 Mankin’s 평분교모형조명현강저(P <0.01)，구유시간의뢰；면역조직화학반응현시，투골소통효낭조화장골관절환조뇨격매형섬용매원격활제、뇨격매형섬용매원격활제수체적양성솔명현강저，이섬용매원격활물억제인자명현승고，구유시간의뢰。Western blot검측결과여면역조직화학구유상동적추세。제시투골소통효낭가능통과조공뇨격매형섬용매원격활제계통대골성관절염발휘방치작용。
BACKGROUND:Tougu Xiaotong capsule is the clinical prescription for the treatment of osteoarthritis, however, its mechanism has not been fuly elucidated. Urokinase type plasminogen activator system which participated in the degradation of the extracelular matrix of articular cartilage and hyperplasia of joint synovium plays an important role in the pathological process of osteoarthritis. OBJECTIVE: To determine the effect ofTougu Xiaotong capsule on urokinase-type plasminogen activator system in knee cartilage tissues of knee osteoarthritis rats. METHODS: Of 144 Sprague-Dawley rats, 120 rats were randomly made into models of knee osteoarthritisvia intra-articular injection of papain, and randomly assigned to model group,Zhuanggu Guanjie Wan group [1.2 g/(kg?d)], low-doseTougu Xiaotong capsule group [0.092 g/(kg?d)], moderate-doseTougu Xiaotong capsule group [0.184 g/(kg?d)] and high-doseTougu Xiaotong capsule group [0.368 g/(kg?d)]. Each group contained 24 rats. Every 2 weeks was considered as a course, with a 2-day interval, totaly 4 courses. The remaining 24 normal rats were included in the blank group. After every two courses, a batch of experimental animals was sacrificed. The pathological changes were observed folowing staining with hematoxylin and eosin. The positive cels of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitor were measured by immunohistochemistry. The protein levels of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitor were measured by western blot assay. RESULTS AND CONCLUSION:Mankin’s score was significantly lower in theTougu Xiaotong capsule group and Zhuanggu Guanjie Wan group compared with the model group (P < 0.01), in a time-dependent manner. Immunohistochemical staining indicated that the positive cels of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor were significantly decreased, but plasminogen activator inhibitor was significantly increased in theTougu Xiaotong capsule group andZhuanggu Guanjie Wangroup in a time-dependent manner. Western blot assay results had an identical trend to immunohistochemistry. These indicated thatTougu Xiaotong capsule showed preventive and therapeutic effects on osteoarthritis by regulating urokinase-type plasminogen activator system.