【摘要】：目的:構(gòu)建四氯化碳誘導(dǎo)的小鼠肝纖維化模型,探討白介素-37對(duì)肝臟纖維化的作用。方法:60只雄性昆明小鼠隨機(jī)均分為6組,即正常對(duì)照組(對(duì)照組),四氯化碳造模組(模型組),空質(zhì)粒A組,空質(zhì)粒B組,IL-37質(zhì)粒干預(yù)組A組(實(shí)驗(yàn)組A組),IL-37質(zhì)粒干預(yù)組B組(實(shí)驗(yàn)組B組),每組又按照處死時(shí)間點(diǎn)(8周,12周)隨機(jī)分成2小組。對(duì)照組:腹腔注射生理鹽水1ml/kg,2次/周,共8周;模型組:腹腔注射40%CCL4溶液1ml/kg,2次/周,共8周;空質(zhì)粒組A組:按模型組造模8周,造模開(kāi)始時(shí)即給予空質(zhì)粒20μg尾靜脈高壓注射,2次/周,共8周;空質(zhì)粒B組:按模型組造模8周后停止注射CCL4,然后每周2次給予空質(zhì)粒20μg尾靜脈高壓注射,共4周;實(shí)驗(yàn)組A組:按模型組造模8周,造模開(kāi)始時(shí)即給予IL-37重組質(zhì)粒20μg尾靜脈高壓注射,2次/周,共8周;實(shí)驗(yàn)組B組:按模型組造模8周后停止注射CCL4,然后每周2次給予IL-37重組質(zhì)粒20μg尾靜脈高壓注射,共4周。8周時(shí)從各組中隨機(jī)選取一半小鼠于注射后禁食24h后處死,取血及肝臟。12周時(shí)同法處死剩余小鼠。行以下檢測(cè):(1)采用BCA法檢測(cè)小鼠肝臟組織總蛋白濃度;(2)ELISA法檢測(cè)小鼠肝組織中的IL-1,IL-6,TNF-α、TGF-β1、Col-Ⅳ、PCⅢ表達(dá)水平;(3)電子天平稱量小鼠肝濕重及體重,計(jì)算肝指數(shù);(4)通過(guò)HE染色觀察小鼠肝臟病理改變。結(jié)果:(1)對(duì)肝組織總蛋白的影響:與對(duì)照組對(duì)比,8周及12周時(shí)模型組肝組織總蛋白水平均明顯減低(P0.05);而實(shí)驗(yàn)組A組肝組織總蛋白水平較模型組高(P0.05)。12周時(shí)實(shí)驗(yàn)組B組肝組織總蛋白水平比模型組高(P0.05)。空質(zhì)粒A組、空質(zhì)粒B組無(wú)論8周還是12周肝組織蛋白濃度同模型組比較無(wú)顯著差異(P0.05)。(2)對(duì)肝組織細(xì)胞因子il-1、il-6、tnf-α、tgf-β1的影響:與對(duì)照組相比,8周及12周時(shí)模型組的il-1、il-6、tnf-α、tgf-β1水平明顯升高(p0.05)。實(shí)驗(yàn)組a組與對(duì)照組相比,il-1、il-6、tnf-α、tgf-β1水平明顯升高(p0.05);與模型組相比il-1、il-6、tnf-α、tgf-β1水平明顯減低(p0.05)。8周及12周時(shí)實(shí)驗(yàn)組b組與對(duì)照組比以上因子水平明顯升高(p0.05),12周時(shí)實(shí)驗(yàn)組b組較模型組il-1、il-6、tnf-α、tgf-β1水平明顯減低(p0.05)�？召|(zhì)粒a組、空質(zhì)粒b組在8周及12周時(shí)上述因子水平同模型組無(wú)顯著差異(p0.05)。(3)對(duì)肝纖指標(biāo)col-Ⅳ、pcⅢ的影響:與對(duì)照組比較,8周及12周時(shí)模型組的col-Ⅳ、pcⅢ水平明顯升高(p0.05)。實(shí)驗(yàn)組a組(8周及12周)與模型組相比col-Ⅳ、pcⅢ水平明顯減低(p0.05)。8周及12周時(shí)實(shí)驗(yàn)組b組的col-Ⅳ、pcⅢ水平較對(duì)照組明顯升高(p0.05),12周時(shí)實(shí)驗(yàn)組b組的col-Ⅳ、pcⅢ水平較模型組明顯減低(p0.05)。8周及12周空質(zhì)粒a組、空質(zhì)粒b組同模型組結(jié)果無(wú)顯著差異(p0.05)。(4)對(duì)肝指數(shù)的影響:與對(duì)照組相比,8周時(shí)及12周時(shí)模型組小鼠肝指數(shù)明顯升高(p0.05);實(shí)驗(yàn)組a組肝指數(shù)較模型組明顯減低(p0.05)。實(shí)驗(yàn)組b組8周時(shí)與對(duì)照組相比,肝指數(shù)升高明顯(p0.05),而與模型組比較肝指數(shù)無(wú)明顯差異(p0.05);12周時(shí)實(shí)驗(yàn)組b組與模型組相比肝指數(shù)明顯減低(p0.05)。(5)肝組織he染色結(jié)果:ishaki肝臟壞死炎癥活動(dòng)評(píng)分示:模型組及空質(zhì)粒組小鼠得分多在(10-14)分,實(shí)驗(yàn)組多為(7-9)分,對(duì)照組均為(0-3)分。模型組與實(shí)驗(yàn)組比較肝臟壞死炎癥活動(dòng)度得分差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。ishaki肝纖維化評(píng)分示模型組得分多在4-5分,實(shí)驗(yàn)組多在2-3分,對(duì)照組均為0分。模型組與實(shí)驗(yàn)組肝纖維化評(píng)分比較有顯著差異(p0.05)。結(jié)論:IL-37能夠減輕CCL4誘導(dǎo)的小鼠肝纖維化,可以有效減輕肝組織炎癥;其抗肝纖維化機(jī)制可能是通過(guò)下調(diào)炎癥因子表達(dá)減輕肝臟炎癥和減少細(xì)胞外基質(zhì)的表達(dá)從而減輕肝纖維化。
[Abstract]:Objective: to construct a model of hepatic fibrosis induced by carbon tetrachloride in mice and explore the effect of interleukin -37 on liver fibrosis. Methods: 60 male Kunming mice were randomly divided into 6 groups, that is, normal control group (control group), carbon tetrachloride model group (model group), empty plasmid A group, empty plasmid B group, A group of IL-37 plasmid intervention group (group A), IL-37 plasmid. Group B of the intervention group (group B of the experimental group), each group was randomly divided into 2 groups according to the time point of death (8 weeks, 12 weeks). The control group was intraperitoneally injected with saline 1ml/kg, 2 times per week, for a total of 8 weeks; the model group was intraperitoneally injected with 40%CCL4 solution 1ml/kg, 2 times per week for 8 weeks; the empty plasmid group A group was given the model group for 8 weeks and the empty plasmid 20 u g tail vein was given at the beginning of the model. Pressure injection, 2 times per week, 8 weeks, empty plasmid B group: after modeling group for 8 weeks to stop injection of CCL4, and then 2 times a week to give empty plasmid 20 mu g tail vein high pressure injection, for a total of 4 weeks, group A: model group for 8 weeks, IL-37 recombinant plasmid 20 mu tail vein high pressure injection, 2 times per week, a total of 8 weeks; experimental group B group: group B group: model group: group B group: group group according to model group: group group: experimental group according to model group After 8 weeks, the injection of CCL4 was stopped, and then 2 times a week, the recombinant plasmid of IL-37 recombinant plasmid was injected with 20 mu g tail vein, and a total of half of the mice were randomly selected from each group for 4 weeks.8 weeks after 24h. The blood and liver.12 weeks were executed with the same method. (1) the total protein concentration of the liver tissue was detected by BCA method (1). 2) ELISA method was used to detect IL-1, IL-6, TNF- alpha, TGF- beta 1, Col- IV, PC III expression in mice liver tissue; (3) electronic balance weighed the wet weight and weight of liver in mice and calculated liver index. (4) the pathological changes of liver in mice were observed by HE staining. (1) the effect of (1) on the total protein of liver tissue: compared with the control group, the total egg of the model group was 8 and 12 weeks at the 8 and 12 weeks. The total protein level of the liver tissue in group A of the experimental group was higher than that in the model group (P0.05). The total protein level of liver tissue in the B group was higher than that in the model group (P0.05). The empty plasmid A group and the empty plasmid B group had no significant difference between the 8 weeks and the 12 weeks of the liver tissue protein concentration in the same model group (P0.05). (2) the cause of liver tissue cell causes was (2). The effects of sub IL-1, IL-6, tnf- a, tgf- beta 1: compared with the control group, the level of IL-1, IL-6, tnf- a, and tgf- beta 1 in the model group increased significantly at the 8 and 12 weeks (P0.05). The a group of the experimental group was significantly higher than the control group, IL-1, IL-6, alpha, and beta 1, compared with the model group. The level of B in the experimental group and the control group was significantly higher than that in the control group (P0.05). At 12 weeks, the level of IL-1, IL-6, tnf- a, tgf- beta 1 in the group B of the experimental group was significantly lower (P0.05). The level of the empty plasmid a group and the empty plasmid B group at 8 and 12 weeks were not significantly different from the model group (P0.05). (3) the effect of the liver fibrin index col- IV and the control group: and the control Group comparison, the level of col- IV and PC III in the model group increased significantly at 8 and 12 weeks (P0.05). The a group (8 and 12 weeks) in the experimental group compared with the model group, col- IV, PC III level decreased significantly (P0.05) in the B group of the experimental group at the.8 weeks and 12 weeks, and the PC III level was significantly higher than the control group (P0.05). At the 12 week, the level III level of the experimental group was compared with the model group. Obviously decreased (P0.05).8 week and 12 week empty plasmid a group, empty plasmid B group had no significant difference in the same model group (P0.05). (4) the liver index in the model group was significantly higher than the control group at 8 weeks and 12 weeks (P0.05); the liver index of the a group in the experimental group was significantly lower than that in the model group (P0.05). The B group in the experimental group was compared with the control group at 8 weeks, The liver index was significantly higher (P0.05), but there was no significant difference in liver index between the model group and the model group (P0.05). The liver index of the B group in the experimental group was significantly lower than that in the model group (P0.05) at 12 weeks. (5) the liver tissue he staining results showed that the scores of the ishaki liver necrosis and inflammation were (10-14) scores in the model group and the empty plasmid group, and the experimental group was (7-9), and the experimental group was more than that of the model group. Compared with the experimental group, the scores of liver necrosis and inflammation were statistically significant (P0.05) in the model group and the experimental group (P0.05) the score of the.Ishaki liver fibrosis score in the model group was more than 4-5 points, the experimental group was 2-3 and the control group was 0. The difference between the model group and the experimental group was significantly different (P0.05). Conclusion: IL-37 can be found. Alleviating liver fibrosis in mice induced by CCL4 can effectively reduce inflammation of liver tissue. The mechanism of anti hepatic fibrosis may be to reduce liver inflammation and reduce the expression of extracellular matrix by down-regulation of inflammatory factors and reduce liver fibrosis.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R575.2

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