重組hIL-10抗家兔皮膚移植反應(yīng)中TLRs的變化
本文選題:重組人白細(xì)胞介素-10 + 皮膚移植 ; 參考:《遵義醫(yī)學(xué)院》2011年碩士論文
【摘要】:目的:通過(guò)觀察rhIL-10作用于同種異體家兔皮膚移植后血清中TLRs的變化,探討TLRs在rhIL-10抗移植排斥反應(yīng)機(jī)制中的作用,為rhIL-10的開發(fā)及應(yīng)用提供實(shí)驗(yàn)依據(jù)。 方法:1.以18只家兔為受體,18只家兔為供體,建立動(dòng)物模型,進(jìn)行異體家兔皮膚移植。移植家兔隨機(jī)分為6組:①組:rhIL-10低劑量組;②組:rhIL-10高劑量組;③組:CsA低劑量組;④組:CsA高劑量組;⑤組:rhIL-10+CsA低劑量聯(lián)合組;⑥組:生理鹽水組。 2.用藥方案:術(shù)前1天開始用藥,每只家兔連續(xù)用藥10天,肌肉注射。 3.各組家兔分別于移植術(shù)前1天、術(shù)后1天、4天、7天、14天、21天、28天取外周血,分離血清,以ELISA方法檢測(cè)血清中TLR4、TLR7、TLR8、TLR9水平。 結(jié)果:1.TLR4檢測(cè)結(jié)果表明:皮膚移植后各組檢測(cè)結(jié)果較術(shù)前均有升高,在術(shù)后14天達(dá)到高峰,其后逐漸下降;術(shù)后4天,⑥組檢測(cè)結(jié)果高于⑤組,差異有統(tǒng)計(jì)學(xué)意義(p0.05) 2.TLR7檢測(cè)結(jié)果表明:皮膚移植后各組檢測(cè)結(jié)果較術(shù)前均有升高,在術(shù)后14天達(dá)到高峰,其后逐漸下降;術(shù)后7天,⑥組檢測(cè)結(jié)果高于其他各組,差異有統(tǒng)計(jì)學(xué)意義(p0.05) 3.TLR8檢測(cè)結(jié)果表明:皮膚移植后各組檢測(cè)結(jié)果較術(shù)前均有升高,在術(shù)后14天達(dá)到高峰,其后逐漸下降;術(shù)后7天,⑥組檢測(cè)結(jié)果高于②組,差異有統(tǒng)計(jì)學(xué)意義(p0.05);⑥組檢測(cè)結(jié)果高于④組,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。 4.TLR9檢測(cè)結(jié)果表明:皮膚移植后各組檢測(cè)結(jié)果較術(shù)前均有升高,在術(shù)后14天其含量達(dá)到高峰,其后逐漸下降,但不同時(shí)間段各組檢測(cè)結(jié)果比較差異無(wú)統(tǒng)計(jì)學(xué)意義。 結(jié)論:1.rhIL-10抗家兔皮膚移植反應(yīng)中,TLR4、TLR7、TLR8、TLR9含量在皮膚移植后明顯升高,表明其可能通過(guò)大量分泌,介導(dǎo)移植后的炎癥反應(yīng),通過(guò)炎癥因子的表達(dá)參與移植排斥反應(yīng)。 2.作為固有免疫分子,當(dāng)免疫應(yīng)答產(chǎn)生效應(yīng)后,排斥反應(yīng)發(fā)生過(guò)程中TLRs檢測(cè)結(jié)果逐漸升高,當(dāng)皮片排斥后達(dá)到高峰,爾后逐漸下降,表明TLRs作為固有免疫因素參與排斥反應(yīng)過(guò)程。 3.TLRs參與移植排斥反應(yīng),因此對(duì)TLRs信號(hào)傳導(dǎo)途徑進(jìn)行干預(yù),可能成為臨床器官移植中抑制免疫排斥反應(yīng)的另一個(gè)可能途徑。
[Abstract]:Objective: to investigate the role of rhIL-10 in the mechanism of anti-graft rejection of rhIL-10 by observing the changes of TLRs in serum after skin allograft in rabbits, and to provide experimental evidence for the development and application of rhIL-10. Method 1: 1. Using 18 rabbits as recipients, 18 rabbits were used as donors to establish animal model and skin allografts were carried out. The transplanted rabbits were randomly divided into 6 groups: group 1, low dose group, group 2, high dose group, group 3, low dose group, group 4, group 1, low dose group, group 2, group 1, group 2, group 1, group 2. Medication plan: 1 day before operation, each rabbit was injected intramuscularly for 10 days. 3. The peripheral blood samples were taken from the rabbits one day before transplantation and one day after transplantation. The serum levels of TLR4, TLR7, TLR8 and TLR9 were detected by ELISA method. Results 1. The results of TLR4 test showed that: after skin transplantation, the results of each group were higher than those of before transplantation, reached the peak at 14 days after operation, and then gradually decreased, and the results in group 6 were higher than those in group 5 on the 4th day after transplantation, the difference was statistically significant (p0.05). The results of 2.TLR7 showed that after skin transplantation, the results of each group were higher than those of before transplantation, reached the peak on the 14th day after operation, and then decreased gradually, and the results of 6 groups were higher than those of the other groups on the 7th day after operation, and the difference was statistically significant (p 0.05). The results of 3.TLR8 showed that after skin transplantation, the results of each group were higher than those of pre-operation, reached the peak on the 14th day after operation, and then decreased gradually, and the results of 6 groups were higher than those of the second group on the 7th day after operation. The difference was statistically significant (P 0.05) and higher than that of 4 groups (P 0.05). The results of 4.TLR9 showed that after skin transplantation, the results of each group were higher than those before transplantation, and reached the peak on the 14th day after operation, and then decreased gradually, but there was no significant difference in the results of each group in different time periods. Conclusion: 1. The content of TLR4, TLR7, TLR8, TLR9 of rhIL-10 in rabbit skin graft response was significantly increased after skin transplantation, indicating that rhIL-10 may mediate the inflammatory response after transplantation through a large amount of secretion, and participate in the graft rejection through the expression of inflammatory factors. 2. As an inherent immune molecule, the results of TLRs detection increased gradually during the process of rejection, reached a peak after skin graft rejection, and then decreased gradually, indicating that TLRs, as an inherent immune factor, participated in the rejection process. 3.TLRs is involved in graft rejection, so intervention of TLRs signaling pathway may be another possible way to inhibit immune rejection in clinical organ transplantation.
【學(xué)位授予單位】:遵義醫(yī)學(xué)院
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2011
【分類號(hào)】:R392.4
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