本文選題：NK細胞 + Graves病��； 參考：《吉林大學(xué)》2016年碩士論文

【摘要】：背景:Graves病(Graves’diseases,GD)是一種器官特異性的自身免疫性疾病,好發(fā)于女性,男女比例大約為1:4-6。目前GD病因不清,發(fā)病機制復(fù)雜而多樣,治療后復(fù)發(fā)率高,因此對發(fā)病機制進行深入研究顯得尤為重要。有研究發(fā)現(xiàn),有多種天然免疫參與了自身免疫性疾病的發(fā)生、發(fā)展。自身免疫性疾病中自身抗體對自身組織的攻擊、T細胞對自身正常細胞的殺傷是導(dǎo)致自身組織破壞的重要因素,而天然免疫對適應(yīng)性免疫具有調(diào)控作用,對B細胞的分化、成熟和分泌免疫球蛋白、T細胞的活化和抗原呈遞均有有重要作用。研究發(fā)現(xiàn)NK細胞活性及其頻率在GD患者外周血中明顯降低,而且,另有研究發(fā)現(xiàn)GD患者在碘131治療后或甲狀腺切除術(shù)后NK細胞活性恢復(fù)正常。盡管眾多研究表明NK細胞在GD的發(fā)病中起重要作用,但是具體機制不清。目的:本課題旨在研究成人初發(fā)未治療GD患者中NK細胞數(shù)量及其功能的變化,觀察其活化性受體與抑制性受體的變化,探討其在GD發(fā)病機制中的作用,為該病的早期診斷、治療、改善預(yù)后、減少復(fù)發(fā)提供新的思路。資料與方法:本研究選擇2012年03月至2014年12月于吉林大學(xué)第一醫(yī)院內(nèi)分泌科就診的新發(fā)Graves病患者28例,其中男性7例,女性21例,年齡18-58周歲,對照組23例,均來自健康獻血者,實驗組、對照組均符合研究人群的納入排除標準。對全部研究對象采血10ml,要求清晨空腹靜脈血。檢測GD患者和健康人外周血中NK細胞及其表面受體的表達,以及其分泌與殺傷功能的測定,并分析其與臨床指標之間的關(guān)系。結(jié)果:1、相較于正常人,GD患者外周血中CD3-CD56+NK細胞(p=0.0107)、CD3-CD16+NK細胞(p=0.0067)、CD3+CD56+NKT細胞(p=0.0017)、CD3+CD16+NKT細胞(p=0.0012)數(shù)量明顯降低。2、相較于正常對照組,在GD患者外周血中NKG2D+(p=0.0099)、NKG2C+(p=0.0120)、NKG2A+(p0.0001)、NKp30+(p=0.0114)NK細胞亞群的數(shù)量明顯減少,而KIR3DL1+(p=0.0119)NK細胞顯著增加。同時發(fā)現(xiàn)NKp44+、NKp46+、KIR2DL3+、CD158a+、CD158b+等NK細胞亞群的細胞數(shù)量與正常對照組無顯著差異(p0.05).3、相較于正常對照組,GD患者活化后的NK細胞中CD107a+(p=0.0278)和IFN-?-secreting NK細胞(p0.0001)顯著減少。但是未刺激的NK細胞中CD107a+(p=0.0278)和IFN-?-secreting NK細胞與正常對照組無差異表達。4、GD患者外周血中的CD3-CD56+NK細胞(p=0.0481 r=0.3768)、CD3-CD16+NK細胞(p=0.0086 r=0.4870)及NKG2D+NK細胞(p=0.0039 r=0.5275)與患者血中的FT4水平呈負相關(guān)。而KIR3DL1+NK細胞(p=0.0028 r=0.5439)則與血中的FT4水平呈正相關(guān).5、NKG2A+NK的數(shù)量與GD患者血清中的TRAb水平呈負相關(guān)(p=0.0220r=0.4311)。而KIR3DL1+NK細胞的數(shù)量與GD患者血清中A-TPO的水平呈正相關(guān)(p=0.0037 r=0.5302)。結(jié)論:1.在GD患者外周血中NK細胞數(shù)量減少,殺傷功能與分泌功能同時受損。2.在GD患者外周血中NK細胞表面活化受體NKG2D、NKG2C、NKp30的數(shù)量明顯減少。3.在GD患者外周血中NK細胞表面抑制性受體KIR3DL 1數(shù)量明顯增加。4.GD患者外周血中的NK細胞與血中的FT4水平呈負相關(guān)。5.GD患者NKG2A+NK的數(shù)量與血清中的TRAb水平呈負相關(guān)。
[Abstract]:Background: Graves's disease (Graves' diseases, GD) is an organ specific autoimmune disease, which is a specific autoimmune disease. The proportion of men and women is about 1:4-6. at present, the etiology of GD is not clear, the pathogenesis is complex and varied, and the recurrence rate is high after treatment. Therefore, it is particularly important to study the mechanism of the disease. With the occurrence and development of autoimmune diseases, the attack of autoantibodies to their own tissues in autoimmune diseases, the killing of T cells to their own normal cells is an important factor leading to the destruction of their own tissues, while natural immunity regulates the adaptive immunity, the differentiation of B cells, the maturation and secretion of immunoglobulin, and T cells Activation and antigen presentation have important effects. The study found that NK cell activity and its frequency decreased significantly in peripheral blood of patients with GD, and other studies have found that NK cell activity in GD patients after iodine 131 treatment or after thyroidectomy was restored to normal. Although numerous studies have shown that NK cells play an important role in the pathogenesis of GD, the specific machine is specific. Objective: the purpose of this study is to study the changes in the number and function of NK cells in the primary untreated GD patients, observe the changes in the active receptor and the inhibitory receptor, explore the role of the cells in the pathogenesis of GD, and provide new ideas for the early diagnosis, treatment, prognosis and reduction of the recurrence of the disease. 28 cases of newly diagnosed Graves disease in Department of endocrinology of No.1 Hospital of Jilin University from 03 months to December 2014 2012 were selected, including 7 male, 21 female, 18-58 years old and 23 control group, all from healthy blood donors, experimental group and control group which were in accordance with the exclusion criteria of the study population. All the subjects were collected for 10ml. The expression of NK cells and their surface receptors in peripheral blood of GD and healthy people, and the determination of their secretion and killing function were measured and the relationship between them and clinical indexes was analyzed. Results: 1, compared to normal people, CD3-CD56+NK cells (P =0.0107), CD3-CD16+NK cells (p=0.0067), CD3+CD56+NKT cells in peripheral blood of GD patients (p=0.0067), CD3+CD56+NKT cells (p=0.0067), CD3+CD56+NKT cells (p=0.0067), and CD3+CD56+NKT cells ( P=0.0017), the number of CD3+CD16+NKT cells (p=0.0012) decreased significantly, compared with the normal control group, the number of NKG2D+ (p=0.0099), NKG2C+ (p=0.0120), NKG2A+ (P0.0001) in the peripheral blood of patients with GD decreased significantly, while the number of.2 cells increased significantly. There was no significant difference between the number of NK cell subsets of b+ and the normal control group (P0.05).3. Compared with the normal control group, the CD107a+ (p=0.0278) and IFN- -secreting NK cells (P0.0001) in the NK cells activated by GD patients decreased significantly. The expression of CD3-CD56+NK cells (p=0.0481 r=0.3768), CD3-CD16+NK cells (p=0.0086 r=0.4870) and NKG2D+NK cells (p=0.0039 r=0.5275) in the peripheral blood of patients with GD were negatively correlated with the level of FT4 in the blood, while the number of CD3-CD56+NK cells was positively correlated with the level of blood. The level of RAb was negatively correlated (p=0.0220r=0.4311). The number of KIR3DL1+NK cells was positively correlated with the level of A-TPO in the serum of GD patients (p=0.0037 r=0.5302). Conclusion: 1. the number of NK cells in the peripheral blood of GD patients is reduced, and the damage and secretion function are simultaneously impaired, and.2. is activated by the receptor on the surface of NK cells in the peripheral blood of GD patients. The number of.3. in the peripheral blood of GD patients significantly decreased the number of NK cell surface inhibitory receptor KIR3DL 1 in the peripheral blood of patients with.4.GD. The number of NK cells in the peripheral blood of patients with.4.GD was negatively correlated with the level of FT4 in the blood. The number of NKG2A+NK in patients with.5.GD was negatively correlated with the level of TRAb in the serum.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R581

【相似文獻】

相關(guān)期刊論文 前10條

1 劉偉紅,金煬縉;Graves病合并骨髓增生異常綜合征一例[J];溫州醫(yī)學(xué)院學(xué)報;2001年05期

2 肖海鵬,余斌杰,王深明,陳國銳;Graves病伴原發(fā)性甲狀旁腺功能亢進癥一例[J];中華內(nèi)科雜志;2002年04期

3 朱大菊,李雪鋒,余紅梅,夏立豐;Graves病合并胰島素自身免疫綜合征一例[J];臨床內(nèi)科雜志;2003年04期

4 古麗拜爾,賀振新;Graves病合并混合性結(jié)締組織病一例[J];實用臨床醫(yī)學(xué);2003年01期

5 黃夥芝;劉莉華;;Graves病伴特發(fā)性血小板減少性紫癜1例報道[J];實用全科醫(yī)學(xué);2006年02期

6 鄺耀麟;;改良的甲狀腺次全切除術(shù)治療Graves病[J];國外醫(yī)學(xué)(創(chuàng)傷與外科基本問題分冊);1984年03期

7 龐久高,陳秋,胡懷東,嚴鐘德;Graves病患者谷氨酸脫羧酶自身抗體的測定及其意義[J];中華內(nèi)分泌代謝雜志;2000年03期

8 侯善榮,史君英,李公寶,劉明德,王玉新,董硯虎;Graves病患者可溶性腫瘤壞死因子受體55水平的監(jiān)測及臨床意義[J];中華內(nèi)分泌代謝雜志;2002年02期

9 唐曉輝,包明業(yè);格林-巴利綜合征合并Graves病及糖尿病1例[J];牡丹江醫(yī)學(xué)院學(xué)報;2002年05期

10 方因,劉昭暉;Graves病并發(fā)甲狀腺微小癌14例臨床分析[J];中國臨床醫(yī)學(xué);2003年05期

相關(guān)會議論文 前10條

1 孟鳳苓;南國珍;蘇勝偶;張會豐;趙志弘;;Graves病患者血清可溶性細胞間粘附分子-1水平的動態(tài)監(jiān)測[A];中華醫(yī)學(xué)會第六次全國內(nèi)分泌學(xué)術(shù)會議論文匯編[C];2001年

2 鄧莉;王德全;陳麗;唐寬曉;;Graves病患者谷氨酸脫羧酶抗體及其它自身抗體的臨床研究[A];中華醫(yī)學(xué)會第六次全國內(nèi)分泌學(xué)術(shù)會議論文匯編[C];2001年

3 鄭文利;張廣森;;血栓性血小板減少性紫癜并Graves病[A];中華醫(yī)學(xué)會血液學(xué)分會第十三屆全國血栓與止血學(xué)術(shù)會議暨“血栓栓塞性疾�。ㄑㄅc止血）基礎(chǔ)與臨床研究進展”論文摘要匯編及學(xué)習(xí)班講義[C];2011年

4 武革;司徒玉;揭育麗;趙玉蘭;陳玉華;甄卓麗;;不同療程對抗甲狀腺藥物治療Graves病復(fù)發(fā)作用的前瞻性研究[A];中華醫(yī)學(xué)會第六次全國內(nèi)分泌學(xué)術(shù)會議論文匯編[C];2001年

5 闞英;王鐵;;~(131)I與抗甲狀腺藥物治療Graves病的比較研究[A];中華醫(yī)學(xué)會第九次全國核醫(yī)學(xué)學(xué)術(shù)會議論文摘要匯編[C];2011年

6 雒文田;郭輝;青才文江;矢野明彥;;自然殺傷T細胞在Graves病發(fā)病中的影響[A];中華醫(yī)學(xué)會第六次全國內(nèi)分泌學(xué)術(shù)會議論文匯編[C];2001年

7 管j;楊忠毅;蔣瑩;;甲狀腺血流彩色多普勒超聲在早期鑒別~(131)I治療Graves病所致的暫時性和永久性甲狀腺功能減退中的價值研究[A];第四屆全國中青年核醫(yī)學(xué)學(xué)術(shù)會議論文匯編[C];2008年

8 馬黎明;邱蘇云;李江城;李進;;中藥協(xié)同~(131)I治療Graves病的臨床研究[A];第三屆全國核素顯像暨核素治療學(xué)術(shù)交流會論文匯編[C];2006年

9 項e，

本文編號：2116816