重組hIL-10抗家兔皮膚移植反應(yīng)中IL-17家族的變化
發(fā)布時(shí)間：2018-08-27 15:52
【摘要】：目的：通過(guò)觀察家兔皮膚移植經(jīng)rhIL-10作用后,血清中IL-17家族因子的變化,探討IL-17家族因子在rhIL-10抗免疫排斥機(jī)制中的作用,為rhIL-10的開(kāi)發(fā)及應(yīng)用提供實(shí)驗(yàn)依據(jù)。 方法：(1)皮膚移植家兔分6組：①rhIL-10低劑量組；②rhIL-10高劑量組；③CsA低劑量組；④CsA高劑量組；⑤rhIL-10+CsA低劑量聯(lián)合組；⑥生理鹽水組。 (2)用藥方案：于術(shù)前1天開(kāi)始用藥,每只家兔連續(xù)10天肌肉注射。 (3)各組分別于術(shù)前1天、術(shù)后1、4、7、14、21、28天取外周血,分離血清,以酶聯(lián)免疫吸附法檢測(cè)移植家兔血清IL-17家族細(xì)胞因子水平。 結(jié)果：(1)IL-17A檢測(cè)結(jié)果表明,各實(shí)驗(yàn)組家兔外周血清IL-17A水平較術(shù)前明顯升高,在術(shù)后14天達(dá)到最高值,與術(shù)前相比差異有統(tǒng)計(jì)學(xué)意義(p0.05),然后逐漸降低；生理鹽水對(duì)照組IL-17A水平比其它組均高,差異有統(tǒng)計(jì)學(xué)意義(p0.05)；rhIL-10高劑量組IL-17A水平較rhIL-10低劑量組低,差異有統(tǒng)計(jì)學(xué)意義(p0.05)；聯(lián)合組比CsA低劑量組、rhIL-10低劑量組均低,且有統(tǒng)計(jì)學(xué)差異(p0.05)；在術(shù)后1天,rhIL-10低劑量組IL-17A水平比CsA低劑量組水平高,且有統(tǒng)計(jì)學(xué)差異(p0.05),但在高劑量組二者無(wú)統(tǒng)計(jì)學(xué)差異(p0.05),在其它時(shí)間點(diǎn),rhIL-10低劑量組與CsA低劑量組之間、rhIL-10高劑量組與CsA高劑量組之間IL-17A水平無(wú)統(tǒng)計(jì)學(xué)差異(p0.05)。 (2)IL-27的檢測(cè)結(jié)果表明,各實(shí)驗(yàn)組家兔外周血清IL-27水平較術(shù)前明顯升高,在術(shù)后14天達(dá)到最高值,與術(shù)前相比差異有統(tǒng)計(jì)學(xué)意義(p0.05),然后逐漸降低；生理鹽水對(duì)照組IL-27水平比其它組均高,且有統(tǒng)計(jì)學(xué)差異(p0.05)；rhIL-10高劑量組IL-27水平較rhIL-10低劑量組水平低,且有統(tǒng)計(jì)學(xué)差異(p0.05)；聯(lián)合組比CsA低劑量組、rhIL-10低劑量組均低,且有統(tǒng)計(jì)學(xué)差異(p0.05)；在術(shù)后1、4、7天rhIL-10低劑量組IL-27水平比CsA低劑量組水平高,且有統(tǒng)計(jì)學(xué)差異(p0.05),在其它時(shí)間,rhIL-10低劑量組IL-27水平與CsA低劑量組相比無(wú)統(tǒng)計(jì)學(xué)差異(p0.05)；rhIL-10高劑量組與CsA高劑量組相比,IL-27平在各檢測(cè)時(shí)間點(diǎn)均無(wú)統(tǒng)計(jì)學(xué)差異(p0.05)。 (3)IL-25的檢測(cè)結(jié)果表明,各實(shí)驗(yàn)組家兔外周血清IL-25水平較術(shù)前明顯升高,生理鹽水對(duì)照組在術(shù)后第4天達(dá)到最高值,其它各實(shí)驗(yàn)組在術(shù)后14天達(dá)到最高值,與術(shù)前相比差異有統(tǒng)計(jì)學(xué)意義(p0.05),然后逐漸降低；在術(shù)后1天,生理鹽水對(duì)照組IL-25水平比其它組高但無(wú)統(tǒng)計(jì)學(xué)差異(p0.05),在術(shù)后4天,生理鹽水對(duì)照組IL-25水平比其它組低但無(wú)統(tǒng)計(jì)學(xué)差異(p0.05),從術(shù)后7天開(kāi)始,生理鹽水對(duì)照組IL-25水平比其它組均低,且有統(tǒng)計(jì)學(xué)差異(p0.05)；除生理鹽水對(duì)照組外,其他各組之間IL-25水平均無(wú)統(tǒng)計(jì)學(xué)差異(p0.05)。 (4)IL-17F檢測(cè)結(jié)果表明,各實(shí)驗(yàn)組外周血IL-17F水平較術(shù)前明顯升高,在術(shù)后14天達(dá)到最高值,與術(shù)前相比差異有統(tǒng)計(jì)學(xué)意義(p0.05),然后逐漸降低；生理鹽水對(duì)照組IL-17F水平比其它組均高,且有統(tǒng)計(jì)學(xué)差異(p0.05)；rhIL-10高劑量組IL-17F水平較rhIL-10低劑量組水平低,且有統(tǒng)計(jì)學(xué)差異(p0.05)；聯(lián)合組比CsA低劑量組、rhIL-10低劑量組均低,且有統(tǒng)計(jì)學(xué)差異(p0.05)；在術(shù)后1天rhIL-10低劑量組IL-17F水平比CsA低劑量組水平高,且有統(tǒng)計(jì)學(xué)差異(p0.05),rhIL-10高劑量組IL-17F水平比CsA高劑量組水高,且有統(tǒng)計(jì)學(xué)差異(p0.05)；在其它時(shí)間,rhIL-10低劑量組與CsA低劑量組,rhIL-10高劑量組與CsA高劑量組之間,IL-17水平無(wú)統(tǒng)計(jì)學(xué)差異(p0.05)。 結(jié)論：(1)IL-17家族細(xì)胞因子在皮膚移植術(shù)后明顯升高,表明IL-17家族細(xì)胞因子可能通過(guò)大量分泌,介導(dǎo)移植后的炎癥反應(yīng),以促進(jìn)炎性因子分泌從而參與移植排斥反應(yīng)；(2)血清中IL-17家族細(xì)胞因子含量變化可以作為移植排斥的診斷與監(jiān)測(cè)指標(biāo)：(3)rhIL-10對(duì)IL-17A、IL-27、IL-17F的抑制與CsA有協(xié)同作用。
[Abstract]:Objective: To observe the changes of IL-17 family factors in serum of rabbits after skin transplantation with rhIL-10, and explore the role of IL-17 family factors in the anti-rejection mechanism of rhIL-10, so as to provide experimental basis for the development and application of rhIL-10.
Methods: (1) Skin transplantation rabbits were divided into 6 groups: (1) rhIL-10 low-dose group; (2) rhIL-10 high-dose group; (3) CsA low-dose group; (4) CsA high-dose group; (6) rhIL-10 + CsA low-dose group; (3) saline group.
(2) medication regimen: 1 days before the operation, each rabbit was injected intramuscularly for 10 consecutive days.
(3) Peripheral blood samples were taken from each group one day before operation and 1,4,7,14,21,28 days after operation. Serum levels of IL-17 family cytokines were detected by enzyme-linked immunosorbent assay.
Results: (1) The results of IL-17A test showed that the levels of IL-17A in peripheral serum of rabbits in each experimental group were significantly higher than those before operation, and reached the highest level at 14 days after operation, which was statistically significant (p0.05), and then gradually decreased. The levels of IL-17A in the saline control group were higher than those in other groups, and the difference was statistically significant (p0.05). The level of IL-17A in the dosage group was lower than that in the low dose group of rhIL-10, and the difference was statistically significant (p0.05); the level of IL-17A in the combined group was lower than that in the low dose group of CsA and the low dose group of rhIL-10 was lower and statistically significant (p0.05); the level of IL-17A in the low dose group of rhIL-10 was higher than that in the low dose group of CsA on the first day after operation, and the difference was statistically significant (p0.05). There was no significant difference in IL-17A levels between rhIL-10 low dose group and CSA low dose group at other time points (p0.05).
(2) The results of IL-27 detection showed that the levels of IL-27 in peripheral serum of rabbits in each experimental group were significantly higher than those before operation, and reached the highest level at 14 days after operation, which was significantly different from those before operation (p0.05), and then gradually decreased; the levels of IL-27 in the control group were higher than those in other groups, and there was a statistically significant difference (p0.05). The level of IL-27 in the combined group was lower than that in the low-dose group of CsA and the low-dose group of rhIL-10 (p0.05). The level of IL-27 in the low-dose group of rhIL-10 was higher than that in the low-dose group of CsA at 1,4,7 days after operation, and the difference was statistically significant (p0.05). There was no significant difference between the levels of IL-27 and CSA low-dose group (p0.05), while there was no significant difference between rhIL-10 high-dose group and CSA high-dose group (p0.05).
(3) The results of IL-25 detection showed that the levels of IL-25 in peripheral serum of rabbits in each experimental group were significantly higher than those before operation, and the levels of IL-25 in normal saline control group reached the highest level on the 4th day after operation, while those in other experimental groups reached the highest level on the 14th day after operation, which was significantly different from those before operation (p0.05), and then decreased gradually on the 1st day after operation. The level of IL-25 in normal saline control group was higher than that in other groups but there was no significant difference (p0.05). On the 4th day after operation, the level of IL-25 in normal saline control group was lower than that in other groups, but there was no significant difference (p0.05). There was no significant difference in average (P0.05).
(4) The results of IL-17F test showed that the levels of IL-17F in peripheral blood of each experimental group were significantly higher than those before operation, and reached the highest level at 14 days after operation, which was significantly different from those before operation (p0.05), and then gradually decreased; the levels of IL-17F in the control group were higher than those in other groups, and there was a statistically significant difference (p0.05); The levels of IL-17F in the combined group were lower than those in the CsA low-dose group and the rhIL-10 low-dose group (p0.05). The levels of IL-17F in the rhIL-10 low-dose group were higher than those in the CsA low-dose group on the first day after operation, and the levels of IL-17F in the rhIL-10 high-dose group were higher than those in the CsA high-dose group (p0.05). At other times, there was no significant difference in the levels of IL-17 between rhIL-10 low-dose group and CSA low-dose group, rhIL-10 high-dose group and CSA high-dose group (p0.05).
CONCLUSIONS: (1) IL-17 family cytokines are significantly elevated after skin transplantation, suggesting that IL-17 family cytokines may be involved in the rejection of skin transplantation by secreting a large number of inflammatory factors to promote the secretion of inflammatory factors; (2) The changes of IL-17 family cytokines in serum may be used as a diagnostic tool for transplant rejection. Monitoring indicators: (3) inhibition of rhIL-10 on IL-17A, IL-27 and IL-17F has synergistic effect with CsA.
【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(lèi)號(hào)】：R392.4
本文編號(hào)：2207742
[Abstract]:Objective: To observe the changes of IL-17 family factors in serum of rabbits after skin transplantation with rhIL-10, and explore the role of IL-17 family factors in the anti-rejection mechanism of rhIL-10, so as to provide experimental basis for the development and application of rhIL-10.
Methods: (1) Skin transplantation rabbits were divided into 6 groups: (1) rhIL-10 low-dose group; (2) rhIL-10 high-dose group; (3) CsA low-dose group; (4) CsA high-dose group; (6) rhIL-10 + CsA low-dose group; (3) saline group.
(2) medication regimen: 1 days before the operation, each rabbit was injected intramuscularly for 10 consecutive days.
(3) Peripheral blood samples were taken from each group one day before operation and 1,4,7,14,21,28 days after operation. Serum levels of IL-17 family cytokines were detected by enzyme-linked immunosorbent assay.
Results: (1) The results of IL-17A test showed that the levels of IL-17A in peripheral serum of rabbits in each experimental group were significantly higher than those before operation, and reached the highest level at 14 days after operation, which was statistically significant (p0.05), and then gradually decreased. The levels of IL-17A in the saline control group were higher than those in other groups, and the difference was statistically significant (p0.05). The level of IL-17A in the dosage group was lower than that in the low dose group of rhIL-10, and the difference was statistically significant (p0.05); the level of IL-17A in the combined group was lower than that in the low dose group of CsA and the low dose group of rhIL-10 was lower and statistically significant (p0.05); the level of IL-17A in the low dose group of rhIL-10 was higher than that in the low dose group of CsA on the first day after operation, and the difference was statistically significant (p0.05). There was no significant difference in IL-17A levels between rhIL-10 low dose group and CSA low dose group at other time points (p0.05).
(2) The results of IL-27 detection showed that the levels of IL-27 in peripheral serum of rabbits in each experimental group were significantly higher than those before operation, and reached the highest level at 14 days after operation, which was significantly different from those before operation (p0.05), and then gradually decreased; the levels of IL-27 in the control group were higher than those in other groups, and there was a statistically significant difference (p0.05). The level of IL-27 in the combined group was lower than that in the low-dose group of CsA and the low-dose group of rhIL-10 (p0.05). The level of IL-27 in the low-dose group of rhIL-10 was higher than that in the low-dose group of CsA at 1,4,7 days after operation, and the difference was statistically significant (p0.05). There was no significant difference between the levels of IL-27 and CSA low-dose group (p0.05), while there was no significant difference between rhIL-10 high-dose group and CSA high-dose group (p0.05).
(3) The results of IL-25 detection showed that the levels of IL-25 in peripheral serum of rabbits in each experimental group were significantly higher than those before operation, and the levels of IL-25 in normal saline control group reached the highest level on the 4th day after operation, while those in other experimental groups reached the highest level on the 14th day after operation, which was significantly different from those before operation (p0.05), and then decreased gradually on the 1st day after operation. The level of IL-25 in normal saline control group was higher than that in other groups but there was no significant difference (p0.05). On the 4th day after operation, the level of IL-25 in normal saline control group was lower than that in other groups, but there was no significant difference (p0.05). There was no significant difference in average (P0.05).
(4) The results of IL-17F test showed that the levels of IL-17F in peripheral blood of each experimental group were significantly higher than those before operation, and reached the highest level at 14 days after operation, which was significantly different from those before operation (p0.05), and then gradually decreased; the levels of IL-17F in the control group were higher than those in other groups, and there was a statistically significant difference (p0.05); The levels of IL-17F in the combined group were lower than those in the CsA low-dose group and the rhIL-10 low-dose group (p0.05). The levels of IL-17F in the rhIL-10 low-dose group were higher than those in the CsA low-dose group on the first day after operation, and the levels of IL-17F in the rhIL-10 high-dose group were higher than those in the CsA high-dose group (p0.05). At other times, there was no significant difference in the levels of IL-17 between rhIL-10 low-dose group and CSA low-dose group, rhIL-10 high-dose group and CSA high-dose group (p0.05).
CONCLUSIONS: (1) IL-17 family cytokines are significantly elevated after skin transplantation, suggesting that IL-17 family cytokines may be involved in the rejection of skin transplantation by secreting a large number of inflammatory factors to promote the secretion of inflammatory factors; (2) The changes of IL-17 family cytokines in serum may be used as a diagnostic tool for transplant rejection. Monitoring indicators: (3) inhibition of rhIL-10 on IL-17A, IL-27 and IL-17F has synergistic effect with CsA.
【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(lèi)號(hào)】：R392.4
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