初探雌激素缺乏对骨关节炎中Notch信号的影响

发布时间：2018-04-16 07:18

  本文选题：骨关节炎 + 雌激素缺乏　； 参考：《重庆医科大学》2017年硕士论文

【摘要】：背景骨关节炎,Osteoarthritis,OA,在当前是一种发病率比较普遍的疾病,其发生在关节区域。由于其导致的剧痛和功能丧失,给患者及其家庭带去了极大的身心痛苦和巨大的经济负担。逐渐增长的研究表明,雌激素水平的降低甚至缺乏与骨关节炎的产生、进展和病变严重程度具有紧密联系。对于关节软骨的生长发育,雌激素具有不可替代的作用。此外,我们发现在其他疾病研究领域中,雌激素在调节Notch信号表达具有重要作用,同时Notch信号分子参与关节软骨细胞的增殖分化和软骨基质的合成,同时Notch信号分子的丧失将会导致骨关节炎的产生。因此,研究雌激素水平的改变和Notch信号表达水平变化是否在骨关节炎退行性变化进程是否具有相关性是一项具有重要意义的任务!。方法将20只均等体重的成年雌性SD大鼠(2月龄)随机均分为四组:双侧卵巢切除+胶原蛋白酶关节腔注射组、双侧卵巢切除组、胶原蛋白酶关节腔注射组和生理盐水关节腔注射组。关节软骨行常规病理组织学染色和免疫组化染色,通过观察关节软骨形态改变和骨关节炎相关生物指标的表达(包括IL-1β,MMP-1和II型胶原蛋白),来评估关节软骨模型的建立。Notch信号的表达情况评估通过免疫组化染色检测Notch2的表达情况来完成。另外,进一步探索骨关节炎标志物与Notch2的相关性。结果两组注射胶原蛋白酶的大鼠关节软骨中均见明显的退行性变化,而两者注射生理盐水的大鼠关节组织中未见明显的关节组织破坏。相比正常雌激素表达水平的骨关节炎组织中,雌激素缺乏情况下的关节软骨损伤区域的Notch信号蛋白分子表达水平明显降低;但是在两组无骨关节炎改变的大鼠关节软骨组织中,不管是否存在雌激素缺乏,均未见Notch的表达。相关性分析表明:Notch2的表达水平与IL-1β和MMP-1表达水平成负相关性;而与Ⅱ型胶原蛋白表达水平呈正相关.结论因此,这些结果暗示雌激素缺乏可能降低骨关节炎关节软骨组织中的Notch信号分子的表达水平。因此,Notch信号通路对于寻找绝经后骨关节炎根治性治疗的方法提供新思路。但是这些结果仍具有争论性,并且需要更多的实验依据作支持,包括细胞研究,蛋白质和基因分析以及雌激素水平的量效和时效作用。
[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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