生长分化因子-15（GDF-15）研究进展

发布时间：2018-03-02 14:45

本文选题：生长分化因子-15　切入点：转化生长因子-β　出处：《山西医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：生长分化因子-15(growth differentiation factor-15, GDF-15)是转化生长因子β(transforming growth factorβ,TGF-β)超家族成员的一个远支,GDF-15是一种应激反应蛋白,生理情况下GDF-15在前列腺和胎盘中高表达,在多数其他组织中微弱表达,包括心脏组织。但是在病理和环境应激情况下,如缺血/再灌注损伤、心脏高压力负荷、心力衰竭[和动脉粥样硬化等,GDF-15在心肌细胞中大量表达,对心肌细胞结构和凋亡程序发挥调节作用,特殊生理病理下,GDF-15表达量也显著上升如手术、缺血、缺氧等引起的心肌、肾、肺或肝损伤,前列腺癌、乳腺癌、结肠癌等肿瘤病灶部位也存在高表达。大量临床与基础研究证实是一个重要的心血管保护因子。作为新的标志物,GDF-15水平与多种心血管疾病的诊断、危险分层和预后判断有密切关系。基础研究GDF-15与心血管疾病的关系主要从以下几方面阐述：1、GDF-15在缺血/再灌注损伤中的表达;2、GDF-15抑制心肌细胞凋亡,保护心脏；3、GDF-15的抗炎效应；4、GDF-15抗心肌肥厚；5、GDF-15抗心力衰竭作用。 GDF-15水平与多种肿瘤密切相关。尽管对各种肿瘤发生时GDF-15水平变化观点不致,大多数研究表明GDF-15在多种肿瘤中表达升高。但从基因及细胞水平均能证实GDF-15能抑制肿瘤细胞生长、侵袭和转移,促进肿瘤细胞凋亡 GDF-15能促进胚胎期鼠的多巴胺能神经元的生存和分化。在体内外都能促进损伤多巴胺能神经元的生存,并且伴随着皮质的损伤在神经元中被诱导。近年来,GDF-15水平与脑血管疾病的关系逐渐受到关注。脑血管疾病及脑损伤等情况下,血清GDF-15水平均升高,并能对疾病严重程度进行预测,然而其保护作用仍有争议。需要进一步临床与基础实验证实本文就GDF-15基因的生物学特点及其与心血管疾病、肿瘤、神经系统疾病等多种疾病的关系和作用作一综述,并分析其可能机制及存在的问题。
[Abstract]:GDF-15 is a member of TGF- 尾 transforming growth factor 尾 (TGF- 尾) superfamily. GDF-15 is an stress response protein. GDF-15 is highly expressed in prostate and placenta under physiological conditions and weakly expressed in most other tissues. Including cardiac tissue. But in pathological and environmental stress conditions, such as ischemia / reperfusion injury, high cardiac pressure load, heart failure [and atherosclerosis, etc.] GDF-15 is expressed heavily in cardiac myocytes, The expression of GDF-15 in cardiac myocytes was also significantly increased under special physiological and pathological conditions, such as myocardial, renal, lung or liver injury, prostate cancer, breast cancer, and so on, caused by surgery, ischemia, hypoxia and so on. There is also high expression in the lesions of colon cancer and other tumors. A large number of clinical and basic studies have proved to be an important cardiovascular protection factor. As a new marker of GDF-15 level and the diagnosis of many cardiovascular diseases, The relationship between GDF-15 and cardiovascular disease is closely related to risk stratification. The anti-inflammatory effect of GDF-15 and its anti-myocardial hypertrophy. 5% GDF-15 anti-heart failure. The level of GDF-15 is closely related to many kinds of tumors. Although there is no point of view of the change of GDF-15 level during the occurrence of various tumors, most studies have shown that the expression of GDF-15 is increased in many kinds of tumors. However, both gene and cell level can prove that GDF-15 can inhibit the growth of tumor cells. Invasion and Metastasis promote apoptosis of tumor cells. GDF-15 can promote the survival and differentiation of dopaminergic neurons in embryonic mice. In recent years, the relationship between GDF-15 level and cerebrovascular disease has been paid close attention to. The serum GDF-15 level is increased in cerebrovascular diseases and brain injury. It can predict the severity of the disease, but its protective effect is still controversial. Further clinical and basic experiments are needed to prove it. In this paper, the biological characteristics of GDF-15 gene and its relationship with cardiovascular diseases, tumors, nervous system diseases and other diseases are reviewed, and the possible mechanism and existing problems are analyzed.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R363

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