本文選題：小鼠巨細(xì)胞病毒 + IL-17��； 參考：《華中科技大學(xué)》2014年博士論文

【摘要】：第一部分炎性因子IL-17在鼠巨細(xì)胞病毒致病機(jī)制中的作用 [目的] 1)建立鼠巨細(xì)胞病毒(Murine cytomegalovirus,MCMV)播散性感染動(dòng)物模型,整體水平觀察炎性因子IL-17在肝臟及唾液腺組織中的表達(dá)情況,探討其在MCMV致病過程中發(fā)揮的作用； 2)應(yīng)用IL-17抗體中和MCMV播散性感染模型小鼠體內(nèi)的炎性因子IL-17,進(jìn)一步研究IL-17在MCMV免疫致病機(jī)制中的地位。 [方法] 1.建立MCMV全身播散性感染模型：選擇4.5周齡的雌性BALB/c小鼠,隨機(jī)分為兩組：MCMV感染組與模擬感染對照組。在MCMV感染后3天、7天、14天和28天各組隨機(jī)選取4只小鼠,給予乙醚麻醉,摘除眼球取血后頸椎脫臼處死,分離血清,無菌收取唾液腺及肝臟組織,部分經(jīng)4%多聚甲醛固定后石蠟包埋,部分組織置于-70℃冰箱保存。 2.病毒滴度測定：取胎鼠胚肺成纖維細(xì)胞作為培養(yǎng)細(xì)胞,采用標(biāo)準(zhǔn)蝕斑試驗(yàn)檢測病毒感染后不同時(shí)間點(diǎn)唾液腺及肝臟組織內(nèi)的感染性病毒滴度。 3.組織內(nèi)IL-17及IL-17R mRNA的表達(dá)：用Trizol法提取唾液腺及肝臟組織總RNA,檢測RNA純度將其逆轉(zhuǎn)錄為cDNA；采用RT-PCR法檢測IL-17及IL-17R mRNA在唾液腺及肝臟組織中的表達(dá)水平。每份樣本同時(shí)檢測目的基因和內(nèi)參GAPDH基因。 4.組織內(nèi)IL-17蛋白表達(dá)：制備組織石蠟切片,采用免疫組織化學(xué)技術(shù)檢測唾液腺及肝臟組織中IL-17的表達(dá)水平與分布特征。 5.組織病理改變：石蠟包埋唾液腺及肝臟組織切片后行蘇木紫-伊紅染色,評估唾液腺及肝臟組織的病理性損傷。 6.血清ALT水平：用羅氏生化分析儀檢測血清ALT水平。 7.IL-17抗體阻斷研究：首先建立MCMV全身播散性感染模型,再腹腔注射IL-17抗體以中和體內(nèi)表達(dá)的IL-17(IL-17阻斷組),同時(shí)設(shè)立正常對照組、MCMV感染對照組和同型抗體對照組,每組小鼠4只。在病毒感染后第7天,各組小鼠給予乙醚麻醉,摘除眼球取血后頸椎脫臼處死,分離血清,無菌收取唾液腺及肝臟組織,部分經(jīng)4%多聚甲醛固定后石蠟包埋,部分唾液腺及肝臟組織置-70℃冰箱保存。用Western-blot法檢測唾液腺及肝臟組織中IL-17蛋白表達(dá)水平；采用標(biāo)準(zhǔn)蝕斑試驗(yàn)檢測組織中MCMV感染性病毒滴度；用RT-PCR法測定組織中IL-17、IL-17R, IFN-y和IL-10基因轉(zhuǎn)錄(mRNA)水平；用HE染色法評估肝臟及唾液腺組織的病理性損傷程度；用羅氏生化分析儀檢測血清ALT水平。 [結(jié)果] 1.組織內(nèi)感染性病毒滴度：唾液腺組織中病毒滴度明顯高于肝臟組織,在病毒感染后第7天明顯升高,并在14天達(dá)到峰值,隨后病毒滴度逐漸減低；而肝臟組織中病毒滴度在感染后第3天升高,第7天病毒滴度明顯降低,在感染后第14天病毒滴度已低于標(biāo)準(zhǔn)蝕斑試驗(yàn)法的檢測水平,無法形成病毒感染性蝕斑。 2.組織病理性損傷：①唾液腺組織：在MCMV感染后第7天,唾液腺組織內(nèi)炎性細(xì)胞浸潤大量出現(xiàn)；在病毒感染后第14天,炎性細(xì)胞浸潤更加明顯,炎性灶逐漸擴(kuò)大,并與鄰近炎性灶相互融合；在病毒感染后28天病理性損傷逐漸減輕,但是仍可見炎性細(xì)胞浸潤；②肝組織：MCMV感染組小鼠肝組織在病毒感染后第3天可見肝細(xì)胞氣球樣變性,嗜酸性變明顯,門管區(qū)可見炎性細(xì)胞浸潤,肝細(xì)胞點(diǎn)狀壞死明顯；感染后第7天病變達(dá)頂峰,肝細(xì)胞嗜酸性變,點(diǎn)灶狀壞死明顯,壞死區(qū)有少量炎性細(xì)胞浸潤,門管區(qū)可見大量炎性細(xì)胞浸潤；隨后病變逐漸緩慢減輕,炎性灶縮小。 3.血清ALT水平：MCMV感染組小鼠血清ALT水平明顯高于正常對照組[(144±11) vs(49.6±5), p0.05]。 4.組織內(nèi)IL-17和IL-17R mRNA表達(dá)：①唾液腺組織：MCMV感染組在感染后各時(shí)間點(diǎn)的IL-17mRNA表達(dá)均高于正常對照組,在MCMV感染后逐漸升高,并在感染后14天明顯高于模擬感染對照組,差異具有統(tǒng)計(jì)學(xué)意義[(0.4103±0.0636) vs(0.245±0.027),p0.05],IL-17在唾液腺組織中的表達(dá)量與唾液腺組織的病理性損傷明顯相關(guān)(R=0.616,p0.05)；IL-17R表達(dá)在MCMV感染后呈現(xiàn)逐漸上升趨勢,并且在感染后第14天明顯高于模擬感染對照組,差異具有統(tǒng)計(jì)學(xué)意義[(0.345±0.012)vs(0.17±0.023),p0.05],其高表達(dá)與唾液腺組織病理性損傷顯著相關(guān)(R=0.751,p0.05)。②肝臟組織：MCMV感染后,肝組織中IL-17mRNA表達(dá)逐漸升高,于感染后7天達(dá)峰值[(0.67±0.104)vs(0.287±0.046),p0.05],14天后緩慢下降,其表達(dá)量與肝臟組織損傷顯著相關(guān)(R=0.773,p0.05)；模擬感染組IL-17R在肝臟組織的表達(dá)相對穩(wěn)定,而MCMV感染組IL-17R表達(dá)在各時(shí)間點(diǎn)均高于模擬感染對照組,感染后呈逐漸上升趨勢,在第7天顯著升高,差異有統(tǒng)計(jì)學(xué)意義[(0.7035±0.0901)vs(0.442±0.112),p0.05)],隨后表達(dá)趨于穩(wěn)定,其表達(dá)量與肝組織損傷明顯相關(guān)(R=0.712,p0.05)。 5.組織內(nèi)IL-17蛋白表達(dá)：MCMV感染組唾液腺組織中IL-17蛋白表達(dá)在感染后逐漸升高并在14天達(dá)到高峰,隨后逐漸降低。IL-17陽性細(xì)胞主要分布在腺管周圍及炎性細(xì)胞浸潤密集部位；感染組肝臟組織在感染后3天IL-17表達(dá)量明顯高于模擬感染組,第7天陽性細(xì)胞數(shù)增加,隨后降低,細(xì)胞主要分布于匯管區(qū)及肝小葉炎性細(xì)胞密集部位。 6.IL-17抗體阻斷實(shí)驗(yàn)：①病毒滴度：與感染對照組及同型抗體對照組相比,IL-17抗體阻斷組在MCMV感染后第7天肝臟組織病毒滴度顯著降低(p0.05),而唾液腺中病毒滴度與MCMV感染對照組及同型抗體對照組比較無明顯差異(p0.05)；②組織內(nèi)IL-17蛋白表達(dá)：IL-17抗體阻斷組肝臟組織IL-17表達(dá)較MCMV感染組及同型抗體對照組比較明顯下降(p0.05),而唾液腺組織IL-17表達(dá)量與MCMV感染組及同型抗體對照組相比差異無統(tǒng)計(jì)學(xué)意義,說明腹腔注射IL-17抗體未能有效中和唾液腺組織中IL-17；③組織病理改變：在病毒感染后第7天,IL-17抗體阻斷組肝組織病理性損傷程度明顯低于MCMV染對照組及同型抗體對照組；而唾液腺組織病理改變與MCMV感染對照組及同型抗體對照組比較無明顯差別。④肝臟組織內(nèi)IL-17、IL-17R、IFN-y和IL-10基因轉(zhuǎn)錄(mRNA)水平：與同型抗體對照組及MCMV感染對照組相比,IL-17抗體阻斷組的IFN-γ[(0.56±0.06) vs(0.55±0.13)vs(0.96±0.2),p0.05]與IL-10[(0.55±0.073)vs(0.51±0.07)vs(0.903±0.18),p0.05]的表達(dá)明顯增加；IL-17表達(dá)明顯降低[(0.77±0.15)vs(0.80±0.14)vs(0.44±0.07),p0.05]；而IL-17R表達(dá)無明顯差異[(0.81±0.16)vs(0.89±0.38)vs(0.87±0.23),p0.05]；⑤血清ALT水平：與MCMV感染對照組及同型抗體對照組相比較,IL-17抗體阻斷組的ALT水平顯著降低[(146±15)vs(102±11)vs(37±12),p0.05]。 [結(jié)論] 1.MCMV感染組織內(nèi)IL-17/IL-17R高表達(dá)與組織病理性損傷嚴(yán)重程度密切相關(guān)；阻斷肝組織IL-17表達(dá)可有效減輕肝組織病理損傷和促進(jìn)肝功能恢復(fù)； 2.感染早期肝組織內(nèi)IL-17相關(guān)免疫反應(yīng)有利于肝臟內(nèi)病毒的清除； 3.腹腔注射IL-17抗體可有效阻斷肝組織中IL-17表達(dá),卻不能中和唾液腺組織中IL-17表達(dá)； 4.唾液腺內(nèi)IL-17受體低表達(dá)與IL-17和IL-17受體表達(dá)高峰延遲等局部免疫特征可能與唾液腺內(nèi)病毒逃避免疫清除機(jī)制有關(guān)； 5.阻斷IL-17表達(dá)后,肝組織IFN-y及IL-10表達(dá)增加,提示三者可相互調(diào)節(jié)而發(fā)揮不同功能。IFN-γ及IL-10高表達(dá)可加速肝組織內(nèi)病毒的清除和減輕炎癥損傷。第二部分MCMV啟動(dòng)Caspase-1信號通路對適應(yīng)性免疫應(yīng)答的影響 [目的] 1.建立MCMV播散型感染動(dòng)物模型,在整體水平觀察Caspase-1信號通路啟動(dòng)情況,初步探討其在MCMV致病過程中的作用； 2.研究Caspase-1信號通路對適應(yīng)性免疫應(yīng)答Th17細(xì)胞的影響 [方法] 1.建立MCMV全身播散型感染動(dòng)物模型：32只4.5周齡雌性BALB/c、鼠被隨機(jī)分為兩組：MCMV病毒感染組與模擬感染對照組。在MCMV感染后3天、7天、14天和28天各組隨機(jī)選取4只小鼠乙醚麻醉摘除眼球取血后頸椎脫臼處死,分離血清,無菌收取脾臟組織,部分經(jīng)4%多聚甲醛固定后石蠟包埋,部分組織置于-70℃冰箱保存； 2.標(biāo)準(zhǔn)蝕斑試實(shí)驗(yàn)檢測脾臟組織中感染性病毒滴度； 3.Western blot檢測脾臟組織中Caspase-1表達(dá)強(qiáng)度； 4.免疫組化法檢測脾組織中IL-1β和IL-18表達(dá)狀況； 5.流式細(xì)胞技術(shù)檢測脾臟組織中Th17細(xì)胞數(shù)量； 6.HE染色法評估脾臟的病理性損傷程度。 [結(jié)果] 1.MCMV感染后,脾臟組織中病毒滴度在感染后第3天已經(jīng)開始升高,第7天病毒滴度逐漸降低,第14天時(shí)用標(biāo)準(zhǔn)空斑實(shí)驗(yàn)已經(jīng)檢測不到病毒； 2.與模擬感染對照組比較,MCMV感染組在感染后第3天脾組織中Caspase-1[(1.483±0.420) vs (0.176±0.045),p0.05]表達(dá)明顯升高后逐漸下降； 3.脾臟組織中IL-1p和IL-18表達(dá)呈進(jìn)行性升高,于感染后7天達(dá)峰值,14天減少,28天基本接近正常； 4.巨細(xì)胞病毒感染后,脾臟的Thl7細(xì)胞逐漸增多,并在感染后第14天達(dá)高峰[(1.14±0.09) vs (0.19±0.04),p0.05],明顯高于模擬感染對照組； 5.脾臟組織病理評估：MCMV感染后第3天,脾臟組織病理損害不明顯,第7天時(shí)白髓淋巴細(xì)胞明顯增生,并出現(xiàn)較多中性粒細(xì)胞與單核細(xì)胞；第14天病變逐漸加重,可見大量巨噬細(xì)胞、出血壞死及纖維條索增生；第28天時(shí)病理損傷明顯減輕。 [結(jié)論] 巨細(xì)胞病毒感染可使脾臟Caspase-1表達(dá)增加,其下游促炎因子IL-1β和IL-18合成和釋放增多,進(jìn)而促進(jìn)Th17細(xì)胞適應(yīng)性免疫應(yīng)答反應(yīng),在清除病毒的同時(shí)也造成了組織免疫病理性損傷。
[Abstract]:Part 1 the role of inflammatory factor IL-17 in the pathogenesis of murine cytomegalovirus
[Objective]
1) to establish an animal model of Murine cytomegalovirus (MCMV) disseminated infection, and to observe the expression of inflammatory factor IL-17 in the liver and salivary glands on the whole level, and to explore its role in the pathogenesis of MCMV.
2) use IL-17 antibody to neutralize the inflammatory factor IL-17 in MCMV mice with disseminated infection, and further study the role of IL-17 in the pathogenesis of MCMV.
[method]
1. the model of MCMV systemic disseminated infection was established: female BALB/c mice of 4.5 weeks of age were selected and randomly divided into two groups: MCMV infection group and simulated infection control group. 4 mice were randomly selected for 3 days, 7 days, 14 days and 28 days after MCMV infection, given ether anesthesia, removal of cervical dislocations after exucleation of blood, separation of serum and asepy collection of salivary glands. And liver tissue, partially paraffin embedded after 4% paraformaldehyde, and partially stored in -70 C refrigerator.
2. virus titer measurement: fetal rat embryo lung fibroblasts were taken as culture cells, and the standard plaque test was used to detect the titer of infected virus in salivary glands and liver tissues at different time points after virus infection.
3. expression of IL-17 and IL-17R mRNA in the tissues: the total RNA of salivary glands and liver tissues was extracted by Trizol, and the purity of RNA was detected by reverse transcription to cDNA, and the expression level of IL-17 and IL-17R mRNA in salivary glands and liver tissues was detected by RT-PCR. The target gene and the internal reference gene were detected at the same time.
The expression of IL-17 protein in 4. tissues: tissue paraffin section was prepared, and the expression and distribution of IL-17 in salivary glands and liver tissues were detected by immunohistochemistry.
5. histopathological changes: paraffin embedded salivary glands and liver tissue sections were stained with hematoxylin eosin staining to assess pathological damage of salivary glands and liver tissues.
6. serum ALT level: serum ALT level was detected by Roche biochemical analyzer.
7.IL-17 antibody blocking study: first to establish a MCMV systemic disseminated infection model, and then intraperitoneally injected with IL-17 antibody to neutralize the IL-17 (IL-17 blockage group) expressed in the body, and set up a normal control group. The control group of MCMV infection and the same type antibody control group, 4 mice in each group. After seventh days of the virus infection, each group of mice is given ether anesthesia and extirpate After the ball was taken from the blood, the dislocated cervical vertebra was executed, the serum was separated, the salivary glands and liver tissues were collected asepsis, part of the paraffin was embedded after 4% polyformaldehyde. Some salivary glands and liver tissues were stored at -70 C fridge. The expression of IL-17 protein in the salivary glands and liver tissues was detected by Western-blot; the standard plaque test was used to detect the MCMV in the tissue. The titer of infectious virus, IL-17, IL-17R, IFN-y and IL-10 gene transcription (mRNA) were measured by RT-PCR, and the degree of pathological damage in the liver and salivary glands was evaluated by HE staining, and the serum ALT level was detected by Roche biochemical analyzer.
[results]
1. the titer of infective virus in the tissue: the virus titer in the salivary gland was significantly higher than that in the liver, and the virus titer increased obviously on the seventh day after the virus infection, and reached the peak at the 14 day, then the virus titer gradually decreased, while the virus titer in the liver tissue increased at third days after infection, and the virus titer decreased significantly on the seventh day, and the virus was the fourteenth day after infection. Titer is lower than the standard plaque test method, and can not form virus infected plaque.
2. tissue pathological injury: (1) salivary gland tissue: inflammatory cell infiltration in salivary glands appeared in the salivary gland on the seventh day after MCMV infection; inflammatory cells infiltrated more obviously on the fourteenth day after virus infection, inflammatory foci gradually expanded and fused with adjacent inflammatory foci; 28 days after the virus infection, the rational damage of the disease gradually lessen, but still Inflammatory cell infiltration was seen in the liver tissue: liver tissue in the liver tissue of the MCMV infection group showed that the liver cells were balloon like degeneration, eosinophilic degeneration was obvious on the third day after virus infection, inflammatory cells infiltrated in the portal area, and the necrosis of the liver cells was obvious. The pathological changes reached the peak at the seventh day after infection, the liver cells were eosinophilic and the focal necrosis was obvious. Necrotic areas were obvious. Necrotic areas were in the necrotic area. A small number of inflammatory cells infiltrated and a large number of inflammatory cells infiltrated in the portal area. Then the lesions gradually slowed down and the inflammatory foci were narrowed.
3. serum ALT level: the serum ALT level of MCMV infected group was significantly higher than that of the normal control group [(144 + 11) vs (49.6 + 5), p0.05].
4. the expression of IL-17 and IL-17R mRNA in the tissues: (1) the salivary gland tissue: the expression of IL-17mRNA in the MCMV infection group was higher than that of the normal control group after infection, and increased gradually after MCMV infection, and was significantly higher than that of the simulated infection control group after infection. The difference was statistically significant [(0.4103 + 0.0636) vs (0.245 + 0.027), p0.05], IL-17 The expression of the salivary gland was significantly correlated with the pathological damage of salivary gland tissue (R=0.616, P0.05). The expression of IL-17R showed a gradual upward trend after MCMV infection, and was significantly higher than that of the simulated infection control group on fourteenth days after infection. The difference was statistically significant [(0.345 + 0.012) vs (0.17 + 0.023), p0.05], and its high expression and saliva The pathological changes of the adeno tissue were significantly correlated (R=0.751, P0.05). After MCMV infection, the expression of IL-17mRNA in the liver tissues increased gradually. The peak value of the liver tissue was 7 (0.67 + 0.104) vs (0.287 + 0.046) after infection, p0.05], decreased slowly after 14 days, and its expression was significantly related to the liver tissue injury (R=0.773, P0.05), and IL-17R in the liver of the simulated infection group was in the liver. The expression of the dirty tissue was relatively stable, and the expression of IL-17R in the MCMV infection group was higher than that of the simulated infection control group at all time points. After infection, the expression increased gradually, and the difference was statistically significant [(0.7035 + 0.0901) vs (0.442 + 0.112), P0.05) at seventh days, and then the expression tended to be stable, and its expression was significantly related to the injury of liver tissue (R=0.71 2, P0.05).
The expression of IL-17 protein in 5. tissues: the expression of IL-17 protein in salivary glands of MCMV infection group increased gradually after infection and reached the peak in 14 days, and then gradually reduced.IL-17 positive cells mainly distributed around the glands and inflammatory cells, and the expression of IL-17 in the liver tissue in the infected group was significantly higher than that of the simulation in 3 days after infection. In the dyed group, the number of positive cells on the seventh day increased, and then decreased.
6.IL-17 antibody blocking experiment: (1) virus titer: compared with the infection control group and the same type antibody control group, the liver tissue virus titer of the IL-17 antibody blockage group decreased significantly (P0.05) at seventh days after MCMV infection, but there was no significant difference between the virus titer in the salivary gland and the MCMV infection control group and the same type antibody control group (P0.05); and (2) the I in the tissue I. The expression of L-17 protein: the expression of IL-17 in the liver tissue of the IL-17 antibody blockage group was significantly lower than that in the MCMV infection group and the same type antibody control group (P0.05), but the expression of IL-17 in salivary gland tissue was not significantly different from that of the MCMV infection group and the same type antibody control group, indicating that the peritoneal injection of IL-17 antibody did not effectively neutralize the IL- in the salivary glands. 17; (3) histopathological changes: in the seventh day after the virus infection, the degree of pathological damage of liver tissue in the IL-17 antibody blockage group was significantly lower than that of the MCMV control group and the same type antibody control group, while the pathological changes of salivary glands were not significantly different from those of the control group of MCMV infection and the same type antibody control group. (4) IL-17, IL-17R, IFN-y and IL in the liver tissue. -10 gene transcription (mRNA) level: compared with the same type antibody control group and the MCMV infection control group, the IFN- gamma (0.56 + 0.06) vs (0.55 + 0.13) vs (0.96 + 0.2), p0.05] and IL-10[(0.55 + 0.073) vs (0.51 + 0.07) vs (0.903 + 0.18), the expression of p0.05] was significantly increased. + 0.07), p0.05], and no significant difference in IL-17R expression [(0.81 + 0.16) vs (0.89 + 0.38) vs (0.87 + 0.23), p0.05]; serum ALT level: compared with MCMV infection control group and Homo antibody control group, the ALT level of IL-17 antibody blockage group was significantly lower [(146 + 15) vs (102 + 11) vs (37 + 12), p0.05].
[Conclusion]
The high expression of IL-17/IL-17R in 1.MCMV infected tissues is closely related to the severity of histopathological injury, and blocking the expression of IL-17 in liver tissue can effectively reduce the pathological damage of liver tissue and promote the recovery of liver function.
2. IL-17 associated immune response in the early stage of liver infection is beneficial to the elimination of virus in the liver.
3. intraperitoneal injection of IL-17 antibody can effectively block the expression of IL-17 in liver tissue, but can not neutralize the IL-17 expression in salivary gland tissue.
4. the low expression of IL-17 receptor in salivary glands and the peak delay of IL-17 and IL-17 receptor expression may be related to the mechanism of virus evasion in salivary glands.
5. the expression of IFN-y and IL-10 in liver tissues increased after blocking the expression of IL-17, suggesting that the three groups could adjust each other and exert different functions of.IFN- gamma and IL-10 to accelerate the clearance of virus in the liver tissue and reduce the inflammatory damage. The effect of Caspase-1 signaling pathway on the adaptive immune response in the second part of MCMV
[Objective]
1. establish MCMV disseminated infection animal model, observe the Caspase-1 signaling pathway at the overall level, and explore its role in the pathogenesis of MCMV.
2. to study the effect of Caspase-1 signaling pathway on adaptive immune response to Th17 cells.
[method]
1. the animal model of MCMV systemic disseminated infection was established: 32 4.5 weeks old female BALB/c, and the rats were randomly divided into two groups: MCMV virus infection group and simulated infection control group. After 3 days of MCMV infection, 7 days, 14 days and 28 days, 4 mice were randomly selected to remove the neck dislocated of the eyeball after exucleation of the eyeball, separate the serum and collect the spleen asepsis group. The parts were woven with paraffin fixed and paraffin embedded, and some of them were stored in -70 C refrigerator. 4%.
2. standard plaque test was used to detect infectious virus titer in spleen tissue.
3.Western blot was used to detect the expression intensity of Caspase-1 in spleen tissue.
4. immunohistochemical staining was used to detect the expression of IL-1 and IL-18 in spleen tissue.
5. the number of Th17 cells in spleen tissue was detected by flow cytometry.
6.HE staining was used to evaluate the degree of pathological injury of the spleen.
[results]
After 1.MCMV infection, the virus titer in the spleen tissues began to rise on the third day after infection, and the titer of the virus gradually decreased on the seventh day. The virus was not detected in the standard air spot test at fourteenth days.
2. compared with the simulated infection control group, the Caspase-1[(1.483 + 0.420) vs (0.176 + 0.045) and the p0.05] expression decreased gradually in the spleen tissue of the MCMV infection group after third days of infection.
3. the expression of IL-1p and IL-18 in spleen tissue progressively increased, and the peak value in 7 Tianda after infection, decreased in 14 days, and basically close to normal in 28 days.
After 4. cytomegalovirus infection, the Thl7 cells of the spleen increased gradually, and the peak of fourteenth Tianda after infection [(1.14 + 0.09) vs (0.19 + 0.04), p0.05], was significantly higher than that of the simulated infection control group.
5. the histopathological evaluation of spleen: third days after MCMV infection, the pathological damage of the spleen was not obvious. At the time of seventh days, the white myeloid lymphocyte proliferation was obvious, and more neutrophils and mononuclear cells appeared, and the pathological changes gradually aggravated on the fourteenth day, and a large number of macrophages, hemorrhage and necrosis and fibrous stripe hyperplasia were seen, and the pathological damage was obviously reduced at twenty-eighth days.
[Conclusion]
Cytomegalovirus infection can increase the expression of Caspase-1 in the spleen, increase the synthesis and release of IL-1 beta and IL-18 in the downstream, and then promote the adaptive immune response of Th17 cells, and cause pathological pathological damage of the tissues at the same time.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R725.1

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本文編號：1988880