本文選題：骨關(guān)節(jié)炎 + 雌激素缺乏��； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景骨關(guān)節(jié)炎,Osteoarthritis,OA,在當(dāng)前是一種發(fā)病率比較普遍的疾病,其發(fā)生在關(guān)節(jié)區(qū)域。由于其導(dǎo)致的劇痛和功能喪失,給患者及其家庭帶去了極大的身心痛苦和巨大的經(jīng)濟(jì)負(fù)擔(dān)。逐漸增長(zhǎng)的研究表明,雌激素水平的降低甚至缺乏與骨關(guān)節(jié)炎的產(chǎn)生、進(jìn)展和病變嚴(yán)重程度具有緊密聯(lián)系。對(duì)于關(guān)節(jié)軟骨的生長(zhǎng)發(fā)育,雌激素具有不可替代的作用。此外,我們發(fā)現(xiàn)在其他疾病研究領(lǐng)域中,雌激素在調(diào)節(jié)Notch信號(hào)表達(dá)具有重要作用,同時(shí)Notch信號(hào)分子參與關(guān)節(jié)軟骨細(xì)胞的增殖分化和軟骨基質(zhì)的合成,同時(shí)Notch信號(hào)分子的喪失將會(huì)導(dǎo)致骨關(guān)節(jié)炎的產(chǎn)生。因此,研究雌激素水平的改變和Notch信號(hào)表達(dá)水平變化是否在骨關(guān)節(jié)炎退行性變化進(jìn)程是否具有相關(guān)性是一項(xiàng)具有重要意義的任務(wù)!。方法將20只均等體重的成年雌性SD大鼠(2月齡)隨機(jī)均分為四組:雙側(cè)卵巢切除+膠原蛋白酶關(guān)節(jié)腔注射組、雙側(cè)卵巢切除組、膠原蛋白酶關(guān)節(jié)腔注射組和生理鹽水關(guān)節(jié)腔注射組。關(guān)節(jié)軟骨行常規(guī)病理組織學(xué)染色和免疫組化染色,通過(guò)觀察關(guān)節(jié)軟骨形態(tài)改變和骨關(guān)節(jié)炎相關(guān)生物指標(biāo)的表達(dá)(包括IL-1β,MMP-1和II型膠原蛋白),來(lái)評(píng)估關(guān)節(jié)軟骨模型的建立。Notch信號(hào)的表達(dá)情況評(píng)估通過(guò)免疫組化染色檢測(cè)Notch2的表達(dá)情況來(lái)完成。另外,進(jìn)一步探索骨關(guān)節(jié)炎標(biāo)志物與Notch2的相關(guān)性。結(jié)果兩組注射膠原蛋白酶的大鼠關(guān)節(jié)軟骨中均見(jiàn)明顯的退行性變化,而兩者注射生理鹽水的大鼠關(guān)節(jié)組織中未見(jiàn)明顯的關(guān)節(jié)組織破壞。相比正常雌激素表達(dá)水平的骨關(guān)節(jié)炎組織中,雌激素缺乏情況下的關(guān)節(jié)軟骨損傷區(qū)域的Notch信號(hào)蛋白分子表達(dá)水平明顯降低;但是在兩組無(wú)骨關(guān)節(jié)炎改變的大鼠關(guān)節(jié)軟骨組織中,不管是否存在雌激素缺乏,均未見(jiàn)Notch的表達(dá)。相關(guān)性分析表明:Notch2的表達(dá)水平與IL-1β和MMP-1表達(dá)水平成負(fù)相關(guān)性;而與Ⅱ型膠原蛋白表達(dá)水平呈正相關(guān).結(jié)論因此,這些結(jié)果暗示雌激素缺乏可能降低骨關(guān)節(jié)炎關(guān)節(jié)軟骨組織中的Notch信號(hào)分子的表達(dá)水平。因此,Notch信號(hào)通路對(duì)于尋找絕經(jīng)后骨關(guān)節(jié)炎根治性治療的方法提供新思路。但是這些結(jié)果仍具有爭(zhēng)論性,并且需要更多的實(shí)驗(yàn)依據(jù)作支持,包括細(xì)胞研究,蛋白質(zhì)和基因分析以及雌激素水平的量效和時(shí)效作用。
[Abstract]:Background Osteoarthritis Osteoarthritis (OAA) is a common disease occurring in the joint area.Because of its severe pain and loss of function, it brings great physical and mental pain and great economic burden to patients and their families.Increasing studies have shown that the decrease or even lack of estrogen level is closely related to the occurrence, progression and severity of osteoarthritis.Estrogen plays an irreplaceable role in the growth and development of articular cartilage.In addition, we have found that estrogen plays an important role in regulating the expression of Notch signal in other diseases, and that Notch signaling molecules are involved in the proliferation and differentiation of articular chondrocytes and the synthesis of cartilage matrix.At the same time, the loss of Notch signaling molecules will lead to osteoarthritis.Therefore, it is an important task to study whether the changes of estrogen level and Notch signal expression are related to the degenerative process of osteoarthritis.Methods Twenty adult female Sprague-Dawley rats of equal weight were randomly divided into four groups: bilateral ovariectomized collagenase injection group and bilateral ovariectomized group.Collagenase injection group and saline injection group.The articular cartilage was stained by routine histopathology and immunohistochemistry.By observing the morphological changes of articular cartilage and the expression of biomarkers associated with osteoarthritis (including IL-1 尾 -MMP-1 and type II collagen), the expression of Notch signal in articular cartilage model was evaluated by immunohistochemical staining.The expression of Notch2 is completed.In addition, to further explore the correlation between osteoarthritis markers and Notch2.Results there were obvious degenerative changes in articular cartilage of rats injected with collagenase, but no obvious damage of articular tissue was found in the rats injected with normal saline.Compared with the osteoarthritis tissue with normal estrogen expression level, the expression of Notch signal protein in the injured area of articular cartilage was significantly decreased in the absence of estrogen, but in the articular cartilage tissue of the rats without osteoarthritis changes, the expression of Notch signal protein in the articular cartilage was significantly lower than that in the normal osteoarthritis tissue.No expression of Notch was found in the presence or absence of estrogen deficiency.The correlation analysis showed that the expression level of IL-1 尾 and MMP-1 was negatively correlated with the expression of Notch2, but positively correlated with the expression of collagen type 鈪，

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