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不同劑量泡球蚴感染所致小鼠肝臟病理變化及其免疫狀態(tài)的研究

發(fā)布時間:2018-04-02 21:27

  本文選題:泡球蚴 切入點:病理類型 出處:《新疆醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的:泡型包蟲病(Alveolar Echinococcosis,AE)是由泡球蚴(Ec-hinococcus multilocularis,Em)寄生人體,導(dǎo)致慢性浸潤性的肝臟損傷為特點的寄生蟲病。(1)通過觀察不同感染時間劑量下泡球蚴對小鼠肝臟所造成的病理損傷、病灶數(shù)量和類型的變化;(2)評估在不同感染劑量下,泡球蚴對小鼠肝臟造成的損傷程度;(3)檢測不同劑量泡球蚴感染條件下CD4+T細胞亞群的變化及炎癥因子基因表達,從而分析宿主不同免疫狀態(tài)下對泡球蚴寄生的影響。方法:(1)給小鼠5種劑量(50psc,250psc,500psc,1000psc,2000psc)泡球蚴達到感染泡球蚴的目的,分別在7個時間段(2周、4周、8周、12周、16周、20周、24周)采集小鼠肝臟標本,制備H E染色片,計算不同時間和劑量下小鼠肝臟病灶數(shù)目和類型;(2)選取3種劑量(50psc,500psc,2000psc),3個感染時間段(2周、12周、24周)小鼠的肝臟的切片進行α-SMA,RS,ki67染色,評估肝臟纖維化水平以及淋巴細胞增殖水平;(3)分離肝臟淋巴細胞,檢測肝臟區(qū)域CD4+T細胞亞群的變化和相關(guān)炎性因子基因的表達水平。結(jié)果:(1)高劑量(2000psc,1000psc)的泡球蚴產(chǎn)生的病灶數(shù)量顯著高于低劑量組(P0.05),病灶數(shù)量不會隨著感染時間延長而減少,反而會增多。并且,病灶面積大,泡球蚴對肝臟侵犯嚴重。但是,低劑量(50psc,250psc)以及中等劑量(500psc)的泡球蚴感染小鼠后,隨著感染時間延長,病灶可以被宿主清除,病灶所引起的局部肝損傷也可以恢復(fù);(2)高劑量組α-SMA以及RS染色的陽性率顯著高于低劑量組(P0.05);2000psc劑量感染后,分別在2周、24周COL1A1和CO L3A1的表達顯著高于正常對照組(P0.05);(3)250psc在不同感染時間點Th1/Th2并無明顯變化,而500psc劑量Th1/Th2在感染24周時顯著升高(P0.05)。2000p sc在24周時Th1/Th2有顯著下降(P0.05);(4).高劑量組和低劑量組在感染晚期(24周)都表現(xiàn)為Treg/Th17平衡向Th17偏移。結(jié)論:(1)低劑量泡球蚴感染小鼠,其病灶可以被宿主清除;但是,高劑量泡球蚴感染小鼠,其病灶不能被清除;(2)高劑量泡球蚴感染小鼠可造成更嚴重的肝纖維化;(3)宿主免疫類型偏向Th1與Th17可能有利于病灶清除。
[Abstract]:Objective: alveolar echinococcosis (Alveolar Echinococcosis, AE) by Echinococcus multilocularis (Ec-hinococcus multilocularis, Em) parasitic body, leading to liver infiltrating the chronic injury to parasitic disease characteristics. (1) the pathological injury by observing the different infection time dose of Echinococcus multilocularis in mice liver caused by changes in the number of dirty. And the type of lesions; (2) in the evaluation of different levels of infection, the extent of damage caused by Echinococcus multilocularis in liver of mice; (3) the change of inflammatory cytokines and gene expression of CD4+T cell subsets and testing different doses of Echinococcus multilocularis infection conditions, so as to analyze the different immune status of the host of Echinococcus multilocularis parasitic effects methods: (1) to the mice of 5 doses (50psc, 250psc, 500psc, 1000psc, 2000psc) of Echinococcus multilocularis infection of Echinococcus multilocularis purpose, in 7 time periods (2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 24 weeks) acquisition of mouse liver preparation of H E staining specimens. Time and dose, different number of mouse liver lesions and the type of calculation; (2) selected 3 doses (50psc, 500psc, 2000psc), with 3 time period (2 weeks, 12 weeks, 24 weeks) in mice liver slices of alpha -SMA, RS, Ki67 staining, assessment of liver fibrosis level lymphocyte proliferation and level; (3) to detect the expression of lymphocytes isolated from the liver, liver area changes of CD4+T cell subsets and related inflammatory factor gene. Results: (1) high dose (2000psc, 1000psc) of Echinococcus multilocularis generated by the number of lesions was significantly higher than that in the low dose group (P0.05), number of lesions and not decreased with the prolongation of infection, but will increase. And the lesion area, the liver Alveococcus seriousviolation. However, low dose (50psc, 250psc), medium dose (500psc) of Echinococcus multilocularis infection in mice after infection with the time prolonged, lesions can be eliminated by host, lesions caused by Partial liver injury can be restored; (2) the positive rate of the high dose group of alpha -SMA and RS staining was significantly higher than the low dose group (P0.05); the dose of 2000psc after infection, respectively, in 2 weeks, 24 weeks and CO COL1A1 expression of L3A1 was significantly higher than that of normal control group (P0.05); (3) 250psc in the same at the time of Th1/Th2 infection did not change significantly, while the 500psc dose of Th1/Th2 infection was significantly increased at 24 weeks (P0.05).2000p SC at 24 weeks Th1/Th2 was significantly decreased (P0.05); (4). High dose group and low dose group in the later stage of infection (24 weeks) showed Treg/Th17 equilibrium shift to Th17. Conclusion: (1) low dose of Echinococcus multilocularis infected mice, the lesions can be eliminated by host; however, high doses of Echinococcus multilocularis infected mice, the lesions cannot be removed; (2) the high dose of Echinococcus multilocularis infected mice can cause more severe hepatic fibrosis; (3) the host immune shows type Th1 and Th17 may is conducive to debridement.

【學(xué)位授予單位】:新疆醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R532.32

【參考文獻】

相關(guān)期刊論文 前10條

1 畢建斌;龐青;王志鑫;王瑞濤;周延巖;劉昊琛;李永壽;王應(yīng)明;樊海寧;張靖W,

本文編號:1702169


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