整合素连接激酶在子宫内膜异位症中的表达及意义

发布时间：2018-08-01 08:32

【摘要】：研究背景及目的：子宫内膜异位症(Endometriosis, EMs)是妇科常见的难治性良性疾病。腹腔镜检查手术仍是目前诊断子宫内膜异位症的金标准。整合素连接激酶(integrin-linked kinase, ILK)是一种丝氨酸/苏氨酸(Sert/Thr)蛋白激酶,是一种具有多种生物学活性的细胞质效应分子,参与了包括整合素通路在内的多种信号通路的调节,它通过与整合素β1亚单位的结合介导细胞与细胞外基质的连接,影响细胞外信号向下游的传递；对细胞的生长、分化、铺展、迁移及细胞凋亡、细胞周期、细胞粘附、增殖等多种生物学行为进行调控。许多证据表明,ILK在包括卵巢癌、乳腺癌及子宫内膜癌等在内的许多激素依赖性肿瘤中表达增多或功能失调。最近的许多研究证明ILK的过表达促进了细胞的转化、生存、上皮问质转化(EMT),相反抑制ILK会降低肿瘤的发生和发展,目前ILK在内异症中的作用机制研究甚少,而子宫内膜异位症属于激素依赖性疾病,因此子宫内膜异位症的发生可能与ILK的表达异常有关。本文通过研究ILK在子宫内膜异位症的在位内膜组织及异位内膜组织中的表达情况,评估ILK在子宫内膜异位症的发病机制中可能起到的作用。方法：应用免疫组织化学染色SP法检测40例子宫内膜异位症组织标本(包括卵巢子宫内膜异位症和卵巢子宫内膜内膜异位症患者的在位内膜)及20例正常子宫内膜组织内ILK的表达情况,比较ILK在子宫内膜异位症在位内膜组织及异位内膜组织中的表达与正常子宫内膜中ILK表达的差异。结果：1、ILK在正常子宫内膜组织中的表达：在正常的子宫内膜细胞的细胞质中ILK低度表达或不表达。ILK在正常子宫内膜中IOD/Area值为：(4.38±0.27)×10^-3,ILK在正常子宫内膜组织增生期IOD/Area值为：(5.42±0.18)×10^-3,ILK在正常子宫内膜组织分泌期IOD/Area值为：(3.35±0.19)×10^-3。ILK在正常子宫内膜组织增生期的表达水平比分泌期的表达水平增高,但两者的差异无明显的统计学意义(p0.05)。 2、ILK在子宫内膜异位症在位内膜中的表达：在EMs在位内膜细胞的细胞质中ILK表达明显增强。ILK在EMs在位内膜中IOD/Area值为：(49.87±2.62)×10^3,ILK在EMs在位内膜增生期的IOD/Area值为：(71.08±1.70)×10^-3,ILK在EMs在位内膜分泌期的IOD/Area值为：(28.65±1.28)×10^-3。ILK在EMs在位内膜增生期的表达水平比分泌期的表达水平明显增高,两者的差异有明显的统计学意义(p0.05), EMs在位内膜ILK的表达比正常子宫内膜中ILK的表达明显增强,差异具有统计学意义(P0.001)。 3、ILK增生期和分泌期的比较(EMs的在位内膜及正常子宫内膜异位症)：在子宫内膜增生期,ILK在EMs在位内膜中的表达比正常子宫内膜中ILK的表达明显增强,差异具有统计学意义(p0.05)。在子宫内膜分泌期,ILK在子宫内膜异位症在位内膜中的表达比正常子宫内膜分泌期表达增强,差异具有明显统计学意义(p0.05)。 4、ILK在子宫内膜异位症患者异位内膜(卵巢子宫内膜异位病灶)中的表达：卵巢子宫内膜异位病灶中ILK在异位内膜细胞的腺体细胞质中表达明显增强。ILK在EMs异位内膜病灶中IOD/Area值为：(92.93±2.98)×10^-3。在卵巢子宫内膜异位病灶中ILK表达比子宫内膜异位症患者的在位内膜中ILK表达增强,差异具有统计学意义(p0.05),并且比正常内膜中ILK表达也增强,差异具有统计学意义(p0.001)。结论：ILK在子宫内膜异位症中的异常表达说明ILK在子宫内膜异位症的发生过程中起一定的作用。
[Abstract]:Background and purpose: Endometriosis (EMs) is a common and refractory benign disease of gynecology. Laparoscopy is still the gold standard for diagnosis of endometriosis. Integrin-linked kinase (ILK) is a kind of serine / threonine (Sert/Thr) protein kinase, which is a kind of multiple protein kinase. Biologically active cytoplasmic effector molecules involved in the regulation of a variety of signaling pathways including integrin pathway, which mediate cells and extracellular matrix through the combination of integrin beta 1 subunits, affecting the transmission of extracellular signals to the downstream, and cell growth, differentiation, spreading, migration and apoptosis, and cell cycle. Many biological behaviors, such as cell adhesion and proliferation, are regulated. Many evidence suggests that ILK has increased or dysfunction in many hormone dependent tumors, including ovarian, breast and endometrial cancers. Many recent studies have shown that the overexpression of ILK promotes cell transformation, survival, and epithelial cell transformation (EMT). Anti inhibition of ILK can reduce the occurrence and development of tumor. At present, the mechanism of ILK in endometriosis is rarely studied. Endometriosis is a hormone dependent disease. Therefore, the occurrence of endometriosis may be related to the abnormal expression of ILK. In this paper, the eutopic and ectopic endometrium of ILK in endometriosis was studied in this paper. The expression of ILK in the membrane tissue may be used to evaluate the possible role of ILK in the pathogenesis of endometriosis.
Methods: the expression of ILK in 40 endometriosis specimens (including endometriosis of ovary endometriosis and endometriosis of ovarian endometriosis) and the expression of ILK in normal endometrium were detected by immunohistochemistry SP method, and the expression of ILK in endometriosis in endometriosis and ectopic endometrium in endometriosis was compared. The difference between the expression of ILK and the expression of normal endometrium in membrane tissue.
Results: 1, ILK expression in normal endometrium: in normal endometrium, ILK low expression or non expression of.ILK in normal endometrium, IOD/Area value is: (4.38 + 0.27) x 10^-3, ILK in normal endometrium hyperplasia phase IOD/Area value: (5.42 + 0.18) x 10^-3, ILK in normal endometrium tissue The IOD/Area value of the secretory phase was (3.35 + 0.19) x 10^-3.ILK in the normal endometrium hyperplasia stage, which was higher than that in the secretory period, but there was no significant difference between them (P0.05).
2, ILK expression in the eutopic endometrium of endometriosis: the expression of ILK in the cytoplasm of EMs eutopic endometrium obviously enhanced the IOD/Area value in the eutopic endometrium of EMs: (49.87 + 2.62) * 10^3, ILK in the eutopic endometrial hyperplasia of ILK, IOD/Area value was: (71.08 + 1.70) x 10^-3, ILK in the secretory phase of eutopic endometrium was: The expression level of (28.65 + 1.28) x 10^-3.ILK in the eutopic endometrium of EMs was significantly higher than that in the secretory phase. The difference between them was statistically significant (P0.05). The expression of ILK in the eutopic endometrium of EMs was significantly higher than the expression of ILK in the normal endometrium, and the difference was statistically significant (P0.001).
3, the comparison of ILK hyperplasia and secretory phase (EMs in eutopic endometrium and normal endometriosis): in endometrial hyperplasia, the expression of ILK in EMs eutopic endometrium is significantly higher than that of ILK in normal endometrium, and the difference is statistically significant (P0.05). In endometriosis, ILK is in endometriosis intima. The expression of P0.05 was higher than that of normal endometrial secretory phase, and the difference was statistically significant (P0.05).
4, ILK expression in endometriosis endometriosis (endometriosis) in patients with endometriosis: the expression of ILK in the glandular cytoplasm of endometriosis cells in endometriosis is obviously enhanced by the expression of.ILK in the EMs ectopic endometrium, IOD/Area value is: (92.93 + 2.98) x 10^-3. in ovarian endometriosis, ILK The expression of ILK in the eutopic endometrium of the patients with endometriosis was enhanced, and the difference was statistically significant (P0.05), and the expression of ILK in the normal endometrium was also enhanced, and the difference was statistically significant (p0.001).
Conclusion: The abnormal expression of ILK in endometriosis suggests that ILK plays a role in the pathogenesis of endometriosis.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R711.71

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