本文選題：慢性阻塞性肺疾病　切入點：胰島素生長因子Ⅰ　出處：《山西醫(yī)科大學》2013年碩士論文

【摘要】：研究目的 近些年來,慢性阻塞性肺疾病(Chronic obstructive pulmonary diseases, COPD)已經(jīng)逐漸成為了一個十分重要的公共衛(wèi)生問題,其主要原因包括患病人數(shù)劇增,死亡率居高不下,從而直接成為一個嚴重的社會經(jīng)濟負擔。更好的了解COPD的分子學和細胞學的發(fā)病機制,可指導許多基礎(chǔ)和臨床的研究方向,從而改進早期診斷方法,尋求干預性靶向治療,發(fā)現(xiàn)“易感”人群及治療急性加重期患者。胰島素生長因子(Insulin-like growth factor, IGF)由于其在細胞分化,細胞增殖以及細胞個體發(fā)育中都表現(xiàn)出十分重要的促進作用,所以具有重要的研究意義,而該因子本身是一類多功能細胞增殖調(diào)控因子。目前已經(jīng)有關(guān)于IGF與生長、代謝、心臟、骨質(zhì)疏松等多個領(lǐng)域的研究,但IGF作為氣道的重塑因子,這方面的研究極少。由于IGF對細胞增殖和凋亡具有雙重調(diào)節(jié)的功能,并且在臨床上,多種慢性疾病及腫瘤多伴隨IGF的異常,因此利用這一因子,發(fā)揮其在診斷和治療中的獨特價值變得由為重要。組織蛋白酶在蛋白降解中起重要作用,它還參與生長因子、血管增殖調(diào)節(jié)及協(xié)助其他細胞因子調(diào)節(jié)等,有助于細胞遷移、增殖及凋亡等的調(diào)節(jié)。組織蛋白酶B(Cathepsin B, CB)是半胱氨酸蛋白水解酶家族中的一員,其引起細胞外基質(zhì)的降解也越來越得到人們的關(guān)注,目前在臨床方面有組織蛋白酶與腫瘤、血管性疾病、腎疾病及骨骼疾病等的研究,有關(guān)組織蛋白酶B在肺部疾病的研究甚少。本實驗通過對COPD患者血清中胰島素生長因子-Ⅰ(IGF-Ⅰ)、胰島素生長因子-Ⅱ(IGF-Ⅱ)及外周血單個核細胞中組織蛋白酶B的測定,可以了解這些因子及蛋白在人體內(nèi)含量的變化及其三者之間的關(guān)系,從而對COPD早期診斷方法及干預性靶向治療提供更多的內(nèi)容。 材料和方法 在我院篩選79例COPD患者及40例健康對照者,抽取靜脈血,應用ELISA方法測定了19例I級、20例II級、21例III級、19例IV級COPD患者和40例健康人血清中IGF-Ⅰ、IGF-Ⅱ的含量,應用Western blot檢測所有研究對象外周血單個核細胞中組織蛋白酶B的含量,由定量數(shù)據(jù)分析其直線相關(guān)關(guān)系。 研究結(jié)果 與對照組相比,COPD組血清中IGF-Ⅰ、IGF-Ⅱ水平均明顯升高(P0.05, P▲0.05); COPD患者血清中IGF-Ⅰ、IGF-Ⅱ水平隨著疾病分級的增加而明顯增加(P0.05,P*0.05)；組織蛋白酶B含量隨著COPD分級的增加而明顯降低,COPD組組織蛋白酶B的表達水平與血清中IGF-Ⅰ、IGF-Ⅱ的水平分別呈負相關(guān)(P0.01,P*0.01)。 結(jié)論 COPD患者血清中IGF-Ⅰ、IGF-Ⅱ含量升高,且隨著疾病分級的增加而明顯增加；COPD患者外周血單個核細胞中的組織蛋白酶B表達下降,且隨COPD分級的增加而明顯降低,組織蛋白酶B表達水平與IGF-Ⅰ、IGF-Ⅱ的含量分別呈負相關(guān),組織蛋白酶B可能通過降解IGF結(jié)合蛋白蛋白酶發(fā)揮作用,從而間接降低IGF-Ⅰ、IGF-Ⅱ的含量。
[Abstract]:Research purposeChronic obstructive pulmonary disease (copd) has become an important public health problem in recent years, mainly due to the sharp increase in the number of people suffering from the disease and the high mortality rate.Thus directly become a serious social and economic burden.A better understanding of the molecular and cytological pathogenesis of COPD can guide many basic and clinical research directions, so as to improve the early diagnosis, seek intervention targeted therapy, and find the "susceptible" population and the treatment of acute exacerbation patients.Insulin-like growth factor (IGF) plays an important role in promoting cell differentiation, cell proliferation and cell ontogeny.And this factor itself is a kind of multifunctional cell proliferation regulation factor.At present, there have been many studies on IGF and growth, metabolism, heart, osteoporosis and so on. However, as airway remodeling factor, IGF is rarely studied.Because IGF has dual regulation function on cell proliferation and apoptosis, and many kinds of chronic diseases and tumors are accompanied by abnormal IGF in clinic, it is important to use this factor to play its unique value in diagnosis and treatment.Cathepsin plays an important role in protein degradation. It also participates in the regulation of growth factor, vascular proliferation and other cytokines, which is helpful to the regulation of cell migration, proliferation and apoptosis.Cathepsin B(Cathepsin B (CBB) is a member of the cysteine proteolytic enzyme family. The degradation of extracellular matrix (ECM) caused by cathepsin B (CBB) has attracted more and more attention.There are few studies on cathepsin B in lung diseases, such as kidney disease and bone disease.In this study, we measured the levels of serum IGF- 鈪，

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