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受體MHC抗原誘導(dǎo)供體胚胎期免疫耐受應(yīng)用于造血干細(xì)胞移植的研究

發(fā)布時(shí)間:2018-03-29 11:08

  本文選題:MHC抗原 切入點(diǎn):胚胎期 出處:《吉林大學(xué)》2009年碩士論文


【摘要】: 通過供體鼠胚胎期卵黃囊內(nèi)途徑接種受體鼠耐受原誘導(dǎo)免疫耐受,達(dá)到供體鼠造血干細(xì)胞對受體鼠的免疫耐受從而預(yù)防移植后GVHD的發(fā)生。本研究通過供體SD大鼠胚胎期卵黃囊內(nèi)接種受體Wistar大鼠外周血單個(gè)核細(xì)胞(豐富表達(dá)MHC抗原);供體SD大鼠出生至性成熟后取其骨髓細(xì)胞移植給受體Wistar大鼠,移植前受體大鼠經(jīng)Co608.0Gy照射清除其自身造血和免疫系統(tǒng),骨髓移植后觀測受體大鼠造血系統(tǒng)和免疫系統(tǒng)變化情況的實(shí)驗(yàn)方法,通過一下幾個(gè)方面對結(jié)果進(jìn)行檢測:外周血白細(xì)胞計(jì)數(shù)和骨髓病理檢測移植后造血恢復(fù)情況,采用PCR方法檢測供體來源sry基因(Y染色體特異的性別決定基因)表達(dá)情況,取各臟器組織病理檢測GVHD情況,采用皮膚移植及單相混合淋巴細(xì)胞反應(yīng)方法檢測受體免疫耐受情況。移植后發(fā)現(xiàn):①實(shí)驗(yàn)組受體Wistar大鼠移植后105d成活率為85%,明顯高于各對照組。②實(shí)驗(yàn)組受體Wistar大鼠照射移植后,白細(xì)胞計(jì)數(shù)經(jīng)曲線變化回升至正常水平,骨髓病理示骨髓增生良好;PCR法可檢測到供體SD大鼠來源的sry基因,說明骨髓移植后受體鼠體內(nèi)重建了供體鼠來源的造血和免疫系統(tǒng)。③實(shí)驗(yàn)組病理檢查僅見程度較輕的GVHD或無GVHD發(fā)生,而對照組可見明顯的GVHD現(xiàn)象。④皮膚移植實(shí)驗(yàn)組受體Wistar大鼠對供體SD大鼠皮膚的移植排斥率較低,與第三無關(guān)供體比較有統(tǒng)計(jì)學(xué)差異;單相混合淋巴細(xì)胞反應(yīng)顯示實(shí)驗(yàn)組淋巴細(xì)胞呈低增值反應(yīng)水平。綜上可見通過供體SD大鼠胚胎期卵黃囊內(nèi)接種耐受原誘導(dǎo)免疫耐受,一定程度上能夠有效的預(yù)防造血干細(xì)胞移植后的GVHD的發(fā)生;供體SD大鼠胚胎期經(jīng)卵黃囊內(nèi)途徑接種單個(gè)核細(xì)胞后,能夠正常出生、存活,實(shí)驗(yàn)方法可行。
[Abstract]:Immunological tolerance was induced by inoculating the recipient mice with the immunoresistance in the yolk sac of donor mice at embryonic stage. To achieve the immune tolerance of donor hematopoietic stem cells to recipient mice and to prevent the occurrence of GVHD after transplantation, this study was conducted by inoculating peripheral blood mononuclear cells (PBMC) of recipient Wistar rats into the embryonic yolk sac of donor SD rats. Bone marrow cells were taken from donor SD rats from birth to sexual maturity and transplanted to recipient Wistar rats. The experimental method of removing autohematopoiesis and immune system by Co608.0Gy irradiation in recipient rats before transplantation and observing the changes of hematopoiesis and immune system in recipient rats after bone marrow transplantation. The results were examined in the following ways: peripheral blood leukocyte count and bone marrow pathological examination of hematopoietic recovery after transplantation, and the expression of donor-derived sry gene Y chromosome specific sex determinant gene by PCR method. GVHD was detected by pathological examination of every organ. Skin transplantation and monophasic mixed lymphocyte reaction were used to detect receptor immune tolerance. It was found that the survival rate of Wistar rats in the experimental group was 855d after transplantation, which was significantly higher than that of Wistar rats. The white blood cell count returned to normal level after curve change. Bone marrow pathology showed that sry gene from donor SD rats could be detected by bone marrow pathology. The results showed that the donor hematopoietic and immune system was reconstructed in the recipient mice after bone marrow transplantation. The pathological examination of the experimental group showed only mild GVHD or no GVHD. In the control group, there was obvious GVHD phenomenon. 4. The skin graft rejection rate of Wistar rats was lower than that of the third unrelated donor group, and there was a significant difference between the experimental group and the third unrelated donor group. The monophasic mixed lymphocyte reaction showed that the lymphocytes in the experimental group showed a low value-added response level, and the immunological tolerance was induced by inoculation of the donor SD rat embryo yolk sac into the yolk sac. To a certain extent, it can effectively prevent the occurrence of GVHD after hematopoietic stem cell transplantation. The donor SD rats can be born and survived after inoculating mononuclear cells through yolk sac in embryonic stage.
【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】:2009
【分類號】:R392.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 李向東;;外周血單個(gè)核細(xì)胞表面表達(dá)MHC分子的研究[J];現(xiàn)代檢驗(yàn)醫(yī)學(xué)雜志;2005年06期

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本文編號:1680866

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