【摘要】：目的：研究右布洛芬聯(lián)合鹽酸氨基葡萄糖對家兔不同時(shí)期骨性關(guān)節(jié)炎的影響,探討聯(lián)合用藥的作用機(jī)制,為臨床研究提供基礎(chǔ)。 方法：將84只新西蘭兔隨機(jī)分為7組(n=84)：假手術(shù)組(A組)、模型組(B組)、右布洛芬組(C組)、鹽酸氨基葡萄糖組(D組)、復(fù)方高組(E組)、復(fù)方中組(F組)、復(fù)方低組(G組),B, C, D, E, F, G組動(dòng)物均在兩側(cè)膝關(guān)節(jié)進(jìn)行造模。麻醉方式是耳緣靜脈注射20%烏拉坦(5m1/kg,無菌條件下在膝關(guān)節(jié)側(cè)髕骨旁切口,分離出內(nèi)側(cè)副韌帶,將內(nèi)側(cè)副韌帶切斷后再切除掉0.5cm左右長度；內(nèi)側(cè)半月板全部切除,傷口縫合。A組的造模條件與其它組相同,只是切開關(guān)節(jié)腔后,不作任何處理,縫合關(guān)節(jié)腔和皮膚。造模后,每只動(dòng)物肌肉注射40萬單位青霉素防止感染,青霉素連續(xù)注射給藥3天。C組灌胃給予25mg/kg右布洛芬溶液,D組灌胃給予60mg/kg鹽酸氨基葡萄糖,E組灌胃給予25+60mg/kg復(fù)方溶液,F組灌胃給予12.5+30mg/kg復(fù)方溶液,G組灌胃給予6.25+15mg/kg復(fù)方溶液,A、B組灌胃給予0.5%CMC溶液。連續(xù)給藥120天,于30、120天分批處死動(dòng)物(30天時(shí)每組處死4只,120天時(shí)每組處死8只),進(jìn)行兔膝關(guān)節(jié)Gotdbrg VM評分；檢測血清中IL-1β、TNF-α、ALP水平含量；關(guān)節(jié)滑液中硫酸軟骨素、磷脂酶A2活性的測定；關(guān)節(jié)軟骨HE染色。 結(jié)果：兔膝關(guān)節(jié)Gotdbrg VM評分結(jié)果顯示,給藥30天與120天,A、B組各指標(biāo)相比均有顯著性差異(p0.05),各給藥組與B組各指標(biāo)比較,有顯著性差異(p0.05)。給藥30天時(shí),血清中IL-1β、TNF-α水平B組明顯高于A組、ALP水平B組明顯低于A組,有顯著性差異(p0.05),給藥組經(jīng)給藥后,血清中IL-1β、TNFα含量水平明顯低于B組、ALP含量水平明顯高于B組,有顯著性差異(p0.05)；關(guān)節(jié)滑液中硫酸軟骨素水平B組明顯低于A組、磷脂酶A2B組明顯高于A組,有顯著性差異(p0.05),給藥組經(jīng)給藥后,關(guān)節(jié)滑液中硫酸軟骨素水平明顯高于B組、磷脂酶A2水平明顯低于B組,有顯著性差異(p0.05)。關(guān)節(jié)軟骨HE染色結(jié)果顯示,與模型組比較,C、D、G組關(guān)節(jié)軟骨損傷評分無顯著性差異,E、F組具有顯著性差異(p0.05)。 結(jié)論：右布洛芬聯(lián)合鹽酸氨基葡萄糖能抑制OA中的IL-1β、TNF-α水平,降低磷脂酶A2活性表達(dá),增加OA病情中ALP、硫酸軟骨素水平,從而改善OA的癥狀,促進(jìn)軟骨細(xì)胞再生,降低軟骨的破壞,進(jìn)而延緩骨性關(guān)節(jié)炎的發(fā)展。
[Abstract]:Aim: to study the effect of dexibuprofen combined with glucosamine hydrochloride on osteoarthritis in rabbits at different stages, and to explore the mechanism of combined use of dexibuprofen and glucosamine hydrochloride in order to provide a basis for clinical study. Methods: 84 New Zealand rabbits were randomly divided into 7 groups: sham operation group (group A), model group (group B), right ibuprofen group (group C), glucosamine hydrochloride group (group D) and compound high dose group (group E). The middle group (F group) and the low group (G group), B, C, D, E, F, G group) were all made models in bilateral knee joints. The anaesthesia method was to inject 20% uratan (5 ml / kg) into the auricular margin and cut off the medial collateral ligament (medial collateral ligament) under aseptic condition. The medial collateral ligament was cut off after the medial collateral ligament was cut off and the left and right length of the 0.5cm was removed. All medial meniscus were excised and wound sutured. Group A had the same model conditions as other groups, only after incision of articular cavity, without any treatment, suture of articular cavity and skin. After modeling, 400000 units of penicillin were injected intramuscularly to prevent infection in each animal. Penicillin was injected continuously for 3 days. Group C was given 25mg/kg dexbuprofen solution, group D was given 60mg/kg glucosamine hydrochloride. Group E was treated with 25 60mg/kg compound solution, group F with 12.5 30mg/kg compound solution, group G with 6.25 15mg/kg compound solution, group A with 0.5%CMC solution. The rabbits were killed in 30120 days (4 in each group at 30 days and 8 in each group at 120 days), and the Gotdbrg VM score of knee joint was evaluated, and the levels of IL-1 尾, TNF- 偽 and ALP in serum were detected. The activity of chondroitin sulfate and phospholipase A 2 in synovial fluid and HE staining in articular cartilage were determined. Results: the Gotdbrg VM score of knee joint of rabbits showed that there were significant differences between 30 days and 120 days of administration, and there were significant differences between each group and B group (p0.05). After 30 days of administration, the serum levels of IL-1 尾 and TNF- 偽 in group B were significantly higher than those in group A, and the level of ALP in group B was significantly lower than that in group A (p0.05). After administration, the serum levels of IL-1 尾 in group B were significantly higher than those in group A (p0.05). The level of TNF 偽 was significantly lower than that of group B, and the level of ALP was significantly higher than that of group B (p0.05). The level of chondroitin sulfate in synovial fluid in group B was significantly lower than that in group A, and the level of chondroitin sulfate in synovial fluid of group B was significantly higher than that in group B (p0.05). The level of phospholipase A 2 was significantly lower than that of group B (p 0.05). The results of HE staining of articular cartilage showed that there was no significant difference in articular cartilage injury score between the two groups, but there was a significant difference between the two groups (p0.05). Conclusion: dexibuprofen combined with glucosamine hydrochloride can inhibit the levels of IL-1 尾 and TNF- 偽 in OA, decrease the activity of phospholipase A2, increase the level of chondroitin sulfate in ALP, in OA, improve the symptoms of OA and promote the regeneration of chondrocytes. Reduce the destruction of cartilage, and then delay the development of osteoarthritis.
【學(xué)位授予單位】：哈爾濱商業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R684.3

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