重组hIL-10抗家兔皮肤移植反应中TLRs的变化

发布时间：2018-04-27 17:43

本文选题：重组人白细胞介素-10 + 皮肤移植　；参考：《遵义医学院》2011年硕士论文

【摘要】：目的：通过观察rhIL-10作用于同种异体家兔皮肤移植后血清中TLRs的变化,探讨TLRs在rhIL-10抗移植排斥反应机制中的作用,为rhIL-10的开发及应用提供实验依据。方法：1.以18只家兔为受体,18只家兔为供体,建立动物模型,进行异体家兔皮肤移植。移植家兔随机分为6组：①组：rhIL-10低剂量组；②组：rhIL-10高剂量组；③组：CsA低剂量组；④组：CsA高剂量组；⑤组：rhIL-10+CsA低剂量联合组；⑥组：生理盐水组。 2.用药方案：术前1天开始用药,每只家兔连续用药10天,肌肉注射。 3.各组家兔分别于移植术前1天、术后1天、4天、7天、14天、21天、28天取外周血,分离血清,以ELISA方法检测血清中TLR4、TLR7、TLR8、TLR9水平。结果：1.TLR4检测结果表明：皮肤移植后各组检测结果较术前均有升高,在术后14天达到高峰,其后逐渐下降；术后4天,⑥组检测结果高于⑤组,差异有统计学意义(p0.05) 2.TLR7检测结果表明：皮肤移植后各组检测结果较术前均有升高,在术后14天达到高峰,其后逐渐下降；术后7天,⑥组检测结果高于其他各组,差异有统计学意义(p0.05) 3.TLR8检测结果表明：皮肤移植后各组检测结果较术前均有升高,在术后14天达到高峰,其后逐渐下降；术后7天,⑥组检测结果高于②组,差异有统计学意义(p0.05)；⑥组检测结果高于④组,差异有统计学意义(p0.05)。 4.TLR9检测结果表明：皮肤移植后各组检测结果较术前均有升高,在术后14天其含量达到高峰,其后逐渐下降,但不同时间段各组检测结果比较差异无统计学意义。结论：1.rhIL-10抗家兔皮肤移植反应中,TLR4、TLR7、TLR8、TLR9含量在皮肤移植后明显升高,表明其可能通过大量分泌,介导移植后的炎症反应,通过炎症因子的表达参与移植排斥反应。 2.作为固有免疫分子,当免疫应答产生效应后,排斥反应发生过程中TLRs检测结果逐渐升高,当皮片排斥后达到高峰,尔后逐渐下降,表明TLRs作为固有免疫因素参与排斥反应过程。 3.TLRs参与移植排斥反应,因此对TLRs信号传导途径进行干预,可能成为临床器官移植中抑制免疫排斥反应的另一个可能途径。
[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.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R392.4

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