本文選題：骨關節(jié)炎 + 骨質疏松��； 參考：《華北理工大學》2017年碩士論文

【摘要】：目的旨在探討成年SD大鼠進行雙側卵巢切除術(Ovariectomy,OVX)模擬人類絕經(jīng)期變化,制造絕經(jīng)后骨關節(jié)炎(Osteoarthritis,OA)模型的可行性;早期應用雷洛昔芬(Raloxifene,RAL)干預絕經(jīng)后OA模型,研究RAL對軟骨下骨及關節(jié)軟骨的作用;并且觀察大鼠年齡相關的關節(jié)變化。方法24只6月齡SPF級SD大鼠隨機分為4組,每組6只,即:Baseline組、Sham+V組、OVX+V組和OVX+RAL組。Baseline組在實驗開始時進行安樂死取材,OVX+V組和OVX+RAL組行雙側OVX手術,Sham+V組進行對照性手術,不進行實質性卵巢切除。術后OVX+RAL組給予RAL 6.2mg/kg·day灌胃,OVX+V組和Sham+V組給予等量生理鹽水灌胃。給藥3月后安樂死動物,4%甲醛固定液固定。所有標本先應用Micro-CT對右側近端脛骨行骨組織形態(tài)學測定;Micro-CT測定完成后,所有動物右膝關節(jié)脫鈣8周,石蠟包埋切片,切片行甲苯胺藍染色和COL-II、Caspase-3,MMP-3免疫組織化學染色。甲苯胺藍染色切片應用OARSI組織學評分;免疫組織化學陽性蛋白表達采用IRS評分。各組數(shù)據(jù)進行相應的統(tǒng)計學分析。結果1 OARSI組織學評分發(fā)現(xiàn),OVX+V組分別與Sham+V組和OVX+RAL組比較除總軟骨退變寬度和關節(jié)囊修復外,所有評分均升高,特別是軟骨基質丟失寬度和顯著軟骨退變寬度顯著升高(P0.05),Sham+V組與Baseline組比較除軟骨基質丟失寬度和顯著軟骨退變寬度評分相同外,所有評分均增加,但無統(tǒng)計學差異。2 OVX+V組分別與Sham+V組和OVX+RAL組比較COL-II表達均顯著降低(P分別0.001和0.001);Sham+V組與Baseline組比較COL-II表達顯著降低(P=0.049)。同樣,OVX+V組分別與Sham+V組和OVX+RAL組比較Caspase-3稍顯升高,但無統(tǒng)計學差異;Sham+V組與Baseline組比較稍顯升高,但無統(tǒng)計學差異。OVX+V組分別與Sham+V組和OVX+RAL組比較MMP-13表達均顯著增加(P均為0.000);Sham+V組與Baseline組比較稍顯升高,但無統(tǒng)計學差異。OVX+V組分別與Sham+V組和OVX+RAL組比較COL-II/Caspase-3和COLII/MMP-13比值均顯著降低(P0.05);Sham+V組與Baseline組比較,COLII/Caspase-3和COL-II/MMP-13比值稍顯降低,其中COL-II/MMP-13有統(tǒng)計學差異(P=0.006)。3 Micro-CT發(fā)現(xiàn),OVX+V組與Sham+V組比較,BV/TV、Tb.N、I.S和BS/TV值均降低,其中I.S具有統(tǒng)計學差異(P=0.022),Tb.Sp和SMI值均增加,但無統(tǒng)計差異。OVX+V組與OVX+RAL組比較,BV/TV、Tb.N、I.S和BS/TV值均顯著降低(P分別=0.001、0.000、0.000和0.002),Tb.Sp和SMI值均顯著增加(P分別=0.012和0.002);Sham+V組與Baseline組比較,BV/TV、Tb.N、I.S和BS/TV值均稍顯降低,Tb.Sp和SMI值均稍顯升高,但無統(tǒng)計學差異。結論1.OVX誘導的軟骨下骨和關節(jié)軟骨退變較為輕微,提示6月齡OVX大鼠是一種退變較為輕微的絕經(jīng)后OA大鼠模型。2.RAL經(jīng)口灌喂3個月可以延緩OVX誘導的絕經(jīng)后軟骨下骨和軟骨退變,并且改善OVX所誘導的關節(jié)囊改變;關節(jié)是一個有機整體,關節(jié)組織間相互作用,RAL對關節(jié)軟骨、軟骨下骨、關節(jié)囊等關節(jié)組織可能都具有積極作用,從關節(jié)整體上延緩OA的疾病進展。3.隨著成年大鼠年齡的增加,軟骨下骨和關節(jié)軟骨退變有加重趨勢。
[Abstract]:Objective to explore the feasibility of Ovariectomy (OVX) in adult SD rats to simulate the changes of human menopause and to make Osteoarthritis (OA) model. Early use of Raloxifene (RAL) to intervene the postmenopausal OA model and study the effect of RAL on the subchondral bone and articular cartilage. Methods 24 6 month old SPF grade SD rats were randomly divided into 4 groups, with 6 rats in each group, that is, group Baseline, group Sham+V, group OVX+V and group OVX+RAL were euthanasia at the beginning of the experiment, OVX+V and OVX+RAL groups underwent bilateral OVX operation, Sham+V group performed controlled surgery without substantial ovarian resection. O after operation Group VX+RAL was given RAL 6.2mg/kg / day for gastric perfusion, and group OVX+V and Sham+V group were given the same amount of normal saline. After March, the animals were euthanized with 4% formaldehyde fixed solution. All specimens were first used to determine the histomorphology of the right proximal tibia with Micro-CT; after Micro-CT, all the animals' right knee joints were decalcified for 8 weeks and paraffin embedded sections. The sections were stained with toluidine blue and immunohistochemical staining of COL-II, Caspase-3 and MMP-3. The histology score of toluidine blue was used in OARSI histology; the expression of immunohistochemical positive protein was evaluated by IRS score. The data of each group were analyzed statistically. The results of 1 OARSI histology were found in the OVX+V group with Sham+V and OVX+RAL groups, respectively. In addition to the total cartilage degeneration width and articular capsule repair, all scores were increased, especially the cartilage matrix loss width and significant cartilage degeneration width increased significantly (P0.05). In group Sham+V and Baseline group, all scores were increased except for the same cartilage matrix loss width and significant cartilage degeneration width score, but no statistical difference was found in.2 group. Compared with group Sham+V and group OVX+RAL, the expression of COL-II was significantly decreased (P 0.001 and 0.001), and the COL-II expression in Sham+V group was significantly lower than that in Baseline group (P=0.049). Similarly, the OVX+V group was slightly higher than the Sham+V group and the OVX+RAL group, but there was no difference between the OVX+V group and the OVX+RAL group, but the group was slightly higher than the Baseline group. Compared with group Sham+V and OVX+RAL group, the expression of MMP-13 was significantly increased in.OVX+V group (P was 0), and in Sham+V group and Baseline group a little increased, but there was no statistical difference between.OVX+V group and Sham+V group and OVX+RAL group. In comparison, the ratio of COLII/Caspase-3 and COL-II/MMP-13 decreased slightly, and COL-II/MMP-13 had statistical difference (P=0.006).3 Micro-CT. The BV/TV, Tb.N, I.S and BS/TV values were all lower in OVX+V group than in Sham+V group. The values of Tb.N, I.S and BS/TV were significantly decreased (P =0.001,0.000,0.000 and 0.002), Tb.Sp and SMI were both significantly increased (P =0.012 and 0.002), and Sham+V and Baseline were slightly lower than those in Baseline group. It changed slightly, suggesting that the 6 month old OVX rat is a mild postmenopausal OA rat model of postmenopausal OA rat model.2.RAL can delay the degeneration of subchondral bone and cartilage induced by OVX, and improve the change of articular capsule induced by OVX; the joint is an organic whole, interarticular intertissue interaction, RAL to articular cartilage and soft tissue. Subosseous bone, joint capsule and other joint tissues may have positive effects. The disease progresses from the joint as a whole, and the disease progression of OA.3. is increased with the age of adult rats, and the degeneration of subchondral bone and articular cartilage is aggravated.

【學位授予單位】：華北理工大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R684.3

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