發(fā)布時(shí)間：2018-06-21 07:57

  本文選題：NKT細(xì)胞 + 免疫耐受　； 參考：《吉林大學(xué)》2011年碩士論文

【摘要】：目的：本實(shí)驗(yàn)探討NKT細(xì)胞在小鼠皮膚移植模型中如何影響口服免疫耐受。目前由于免疫抑制劑高效性和臨床廣泛應(yīng)用使同種異體移植進(jìn)步顯著,移植物存活時(shí)間延長,排斥率明顯降低。但是長期以來,由于免疫抑制劑的毒副作用及排異反應(yīng),嚴(yán)重影響了移植物的長期存活和受者的生存質(zhì)量。因此誘導(dǎo)特異性移植耐受,減少排斥反應(yīng),避免免疫抑制劑的毒副作用及解決移植器官長期存活成為焦點(diǎn)。大量實(shí)驗(yàn)表明,通過術(shù)前口服供體抗原可以誘導(dǎo)移植免疫耐受。NKT細(xì)胞是一類具有獨(dú)特生物學(xué)活性的細(xì)胞亞群,在移植免疫耐受的形成中扮演著重要的角色。 方法：建立同種異體小鼠尾-背皮膚移植模型,受鼠分別給予供體脾淋巴細(xì)胞灌胃,腹腔注射環(huán)孢素及供體脾淋巴細(xì)胞灌胃和環(huán)孢素腹腔注射聯(lián)合應(yīng)用,術(shù)后觀察移植皮膚存活狀況。應(yīng)用流式細(xì)胞技術(shù)檢測(cè)各組小鼠脾細(xì)胞中NKT細(xì)胞變化,并提取產(chǎn)生免疫耐受的小鼠的NKT細(xì)胞,過繼性轉(zhuǎn)移輸注給正常受鼠,再行皮膚移植,觀察移植皮膚存活時(shí)間,進(jìn)一步研究NKT細(xì)胞誘導(dǎo)耐受情況。 結(jié)果： (1)對(duì)照組小鼠移植皮片平均存活時(shí)間(MST)為12天,單純口服組、單純CSA組、口服+環(huán)孢素組的皮片存活時(shí)間分別為15天,14天和16.5天。與對(duì)照組比較,單純CSA組皮片存活時(shí)間顯著延長(P0.0001)；而與對(duì)照組比較,單純口服組皮片存活時(shí)間也有顯著延長(P0.0001),且誘導(dǎo)免疫耐受的效果優(yōu)于單純CSA組(P0.05)�？诜�+CSA組皮片移植物存活時(shí)間明顯優(yōu)于單純口服組(P0.01)及單純CSA組(P0.05)。 (2)流式細(xì)胞技術(shù)檢測(cè)受鼠脾細(xì)胞中NKT細(xì)胞(NK1.1+CD3+)的百分比。與對(duì)照組比較,單純CSA組脾細(xì)胞中NKT細(xì)胞百分比無顯著變化,而單純口服組,NKT細(xì)胞顯著增加,P0.05；與單純口服組比較,口服+CSA組NKT細(xì)胞百分比顯著增加,P0.05；與對(duì)照組比較,NKT細(xì)胞百分比增加更為明顯,P0.001。 (3)提取產(chǎn)生免疫耐受的小鼠的NKT細(xì)胞,并給予另一組小鼠鼠尾靜脈過繼轉(zhuǎn)移輸注,再行皮膚移植,移植皮膚較對(duì)照組的存活期明顯延長(P0.001)。 結(jié)論：通過口服供體抗原結(jié)合免疫抑制劑腹腔注射可以誘導(dǎo)小鼠同種異體皮膚免疫耐受,免疫耐受后受體脾細(xì)胞中NKT細(xì)胞明顯增加,過繼性轉(zhuǎn)移輸注耐受小鼠的NKT細(xì)胞可以誘導(dǎo)野生型小鼠的皮膚移植免疫耐受。
[Abstract]:Objective : To investigate the effect of NKT cells on oral immune tolerance in mouse skin transplantation model .


Methods : The rat tail - back skin transplantation model was established , and the mice were given donor spleen lymphocyte lavage , intraperitoneal injection of cyclosporin and donor spleen lymphocytes . The survival of transplanted skin was observed . The NKT cells were detected by flow cytometry . The NKT cells in the spleen cells of each group were detected by flow cytometry . The survival time of transplanted skin was observed and the tolerance of NKT cells was further studied .


Results :


( 1 ) The average survival time ( MST ) of the grafts in control group was 12 days . The survival time of the skin grafts was 15 days , 14 days and 16.5 days in the simple oral group and the simple CSA group . Compared with the control group , the survival time of the only CSA group was significantly prolonged ( P0.01 ) .
Compared with the control group , the survival time of the simple oral group was significantly prolonged ( P < 0.01 ) , and the effect of inducing immune tolerance was better than that of the simple CSA group ( P0.05 ) . The survival time of the oral + CSA group was obviously better than that of the simple oral group ( P0.01 ) and the simple CSA group ( P0.05 ) .


( 2 ) The percentage of NKT cells ( NK1 . 1 + CD3 + ) in spleen cells was detected by flow cytometry . Compared with the control group , the percentage of NKT cells in the spleen cells of the simple CSA group was not significantly changed , while only the NKT cells increased significantly in the simple oral group ( P0.05 ) .
Compared with the simple oral group , the percentage of NKT cells in oral and CSA group was significantly increased ( P0.05 ) .
Compared with the control group , the percentage of NKT cells increased more obviously , P0.001 .


( 3 ) The NKT cells were extracted from the mice with immune tolerance , and the other group of mice were given the adoptive transfer infusion of tail vein , then skin transplantation was performed , and the survival time of the transplanted skin was significantly prolonged compared with the control group ( P0.001 ) .


Conclusion : The immune tolerance of allogeneic skin can be induced by intraperitoneal injection of oral donor antigen and immune inhibitor , and the NKT cells in the spleen cells of the receptor after immune tolerance increase obviously , and the NKT cells in the adoptive transfer infusion tolerance mice can induce the immune tolerance of skin graft in wild type mice .
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R392.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 馬群;李春霞;明建擴(kuò);;供體NKT細(xì)胞輸注促進(jìn)小鼠皮膚移植耐受及其機(jī)理的研究[J];濟(jì)寧醫(yī)學(xué)院學(xué)報(bào);2007年04期

2 呂艷,謝蜀生,張慶殷,郝潔,高翔;供體脾細(xì)胞輸注誘導(dǎo)小鼠移植耐受及其機(jī)理的研究[J];中華微生物學(xué)和免疫學(xué)雜志;2001年02期

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本文編號(hào)：2047818