本文關(guān)鍵詞： 帕金森病 1-甲基-4-苯基-1 2 3 6-四氫吡啶 輔助性T細胞17 髓系抑制性細胞 神經(jīng)炎性　出處：《江蘇大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:通過對輔助性T細胞17(Th17)和髓系抑制性細胞(MDSC)在初診帕金森病(PD)患者、PD小鼠模型中表達及相關(guān)性的檢測,探究Th17和MDSC在PD病程中的表達情況并闡明二者在PD中的作用機制。方法:1、收集臨床上初診且未行相關(guān)抗PD治療的PD患者32例作為PD組,采用Hoehr-Yahr分級和統(tǒng)一帕金森病評定量表評價患者病情的嚴重程度,并選入32名同年齡段體檢正常的健康志愿者作為對照組。流式細胞儀檢測兩組人員外周血Th17和MDSC的細胞百分率,并分析Th17、MDSC和PD病情嚴重程度間的相關(guān)性。2、選擇C57BL/6小鼠40只隨機平均分為PD組、PD+吉西他濱組、吉西他濱組和對照組。PD組和PD+吉西他濱組小鼠予1-甲基-4-苯基-1,2,3,6-四氫吡啶(MPTP)建立PD模型,PD+吉西他濱組和吉西他濱組小鼠另予吉西他濱腹腔注射,對照組小鼠予相同劑量生理鹽水腹腔注射。通過小鼠一般運動情況(震顫、運動、步態(tài)、毛發(fā)等表現(xiàn))、行為學(xué)實驗(爬桿實驗、懸掛實驗、強迫游泳實驗)、免疫組化檢測中腦黑質(zhì)區(qū)酪氨酸羥化酶(TH)陽性細胞數(shù)來評價PD小鼠模型建立情況。流式細胞儀檢測各組小鼠脾臟懸液中Th17和MDSC的細胞百分率,并分析二者之間的相關(guān)性。結(jié)果:1、在PD患者外周血中,Th17和MDSC的細胞百分率較對照組明顯升高,且二者升高程度呈正相關(guān),結(jié)果均有顯著差異。而Th17和MDSC與PD病情嚴重程度間未呈現(xiàn)相關(guān)性。2、MPTP建立的PD小鼠均出現(xiàn)不同程度的運動能力減退和運動行為異常。行為學(xué)實驗中,相較于吉西他濱組和對照組,PD組和PD+吉西他濱組的小鼠在爬桿實驗中調(diào)頭與爬桿時間延長,懸掛實驗中懸掛時間減少,強迫游泳實驗中靜止時間延長,結(jié)果均有顯著差異。PD組和PD+吉西他濱組、吉西他濱組和對照組之間各行為學(xué)實驗檢查指標無明顯差異。中腦黑質(zhì)區(qū)TH細胞染色中,PD組和PD+吉西他濱組小鼠中腦黑質(zhì)區(qū)TH細胞數(shù)量較吉西他濱組和對照組小鼠減少,結(jié)果具有顯著差異。3、Th17細胞百分率在PD組小鼠脾臟懸液中較吉西他濱組和對照組升高,PD+吉西他濱組小鼠脾臟懸液中Th17細胞百分數(shù)較其余三組升高,結(jié)果均有顯著差異。吉西他濱組和對照組之間無明顯差異。4、MDSC細胞百分率在PD組小鼠脾臟懸液中較其他三組升高,在PD+吉西他濱組較吉西他濱組和對照組升高,結(jié)果均有顯著差異。吉西他濱組和對照組之間無明顯差別。5、在PD小鼠模型脾臟懸液中,各組Th17和MDSC未呈現(xiàn)相關(guān)性。結(jié)論:1、PD中存在神經(jīng)免疫炎性反應(yīng),Th17與MDSC參與了該病理機制。2、在初診PD患者外周血中,Th17與MDSC的表達較健康人明顯升高。3、本研究中PD模型建立成功,且吉西他濱在PD模型中未對PD病理和癥狀產(chǎn)生明顯影響。4、在PD小鼠模型的脾臟懸液中,Th17與MDSC的表達較正常小鼠明顯升高。5、Th17和MDSC可能共同參與并促進了PD炎性反應(yīng)的發(fā)生發(fā)展。6、在MPTP建立的亞急性PD小鼠模型中,MDSC可發(fā)揮其免疫調(diào)節(jié)作用抑制Th17擴增。
[Abstract]:Objective: to investigate the expression and correlation of helper T cell 17 (T17) and myeloid suppressor cell (MDSC) in PD mice with newly diagnosed Parkinson's disease (PD). To investigate the expression of Th17 and MDSC in the course of PD and to elucidate the mechanism of their action in PD. Method: 1. A total of 32 PD patients who were newly diagnosed and not treated with anti-PD were selected as PD group. The severity of the disease was evaluated by Hoehr-Yahr grading and unified Parkinson's disease rating scale. 32 healthy volunteers of the same age were selected as control group. Flow cytometry was used to detect the percentage of Th17 and MDSC in peripheral blood of the two groups, and Th17 was analyzed. The correlation between MDSC and severity of PD. 2. Forty C57BL / 6 mice were randomly divided into PD group and PD gemcitabine group. PD model was established with 1-methyl-4-phenyl-1-trihydropyridine-6-tetrahydropyridine (MPTP) in mice of gemcitabine group and control group (PD group and PD gemcitabine group). Mice in PD gemcitabine group and gemcitabine group were intraperitoneally injected with gemcitabine, while mice in control group were intraperitoneally injected with the same dose of normal saline. Hair and other manifestations, behavioral experiments (climbing test, hanging experiment, forced swimming experiment). Immunohistochemical detection of tyrosine hydroxylase in substantia nigra. To evaluate the establishment of PD mouse model, the percentage of Th17 and MDSC in spleen suspension of each group was detected by flow cytometry. Results the percentage of Th17 and MDSC cells in peripheral blood of PD patients was significantly higher than that of control group, and there was a positive correlation between them. There was no correlation between Th17 and MDSC and the severity of PD. PD mice established by MPTP showed different degrees of motor dysfunction and abnormal motor behavior. In behavioral experiment, compared with gemcitabine group and control group. PD group and PD gemcitabine group of mice in the climbing rod test in the rotation and climbing time prolonged, suspension test in the suspension time decreased, forced swimming test in the static time prolonged. Results there were significant differences between PD group and PD gemcitabine group. There was no significant difference in the behavioral parameters between the PD group and the control group. In the th cell staining of substantia nigra area of the mesencephalon, there was no significant difference between the two groups. The number of th cells in substantia nigra of PD group and PD gemcitabine group was significantly lower than that in gemcitabine group and control group. The percentage of Th17 cells in spleen suspension of PD group was higher than that of gemcitabine group and control group. The percentage of Th17 cells in spleen suspension of PD gemcitabine group was higher than that of other three groups. There was no significant difference between the gemcitabine group and the control group. The percentage of MDSC cells in the spleen suspension of PD group was higher than that of the other three groups. In PD gemcitabine group compared with gemcitabine group and control group, the results were significantly different. There was no significant difference between gemcitabine group and control group. There was no correlation between Th17 and MDSC in each group. Conclusion Th17 and MDSC are involved in the pathological mechanism of PD. Conclusion Th17 and MDSC are involved in the peripheral blood of patients with PD. The expression of Th17 and MDSC was significantly higher than that of healthy subjects. The PD model was successfully established in this study, and gemcitabine had no significant effect on pathology and symptoms of PD in PD model. The expression of Th17 and MDSC in spleen suspension of PD mice was significantly higher than that in normal mice. Th17 and MDSC may be involved in and promote the development of PD inflammatory response. 6, in the subacute PD mouse model established by MPTP. MDSC can exert its immunomodulatory function to inhibit Th17 amplification.
【學(xué)位授予單位】：江蘇大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R742.5

【參考文獻】

相關(guān)期刊論文 前10條

1 王瑩雪;卞育婕;周玉奇;崔逸爽;周國龍;魏子峰;張宇新;王茜;;帕金森病動物模型神經(jīng)炎癥反應(yīng)與損傷的研究進展[J];神經(jīng)解剖學(xué)雜志;2017年01期

2 邵春青;李兆倫;劉志偉;張國軍;;血腦屏障完整性及鞘內(nèi)IgG合成率在中樞神經(jīng)系統(tǒng)疾病診斷中的應(yīng)用[J];檢驗醫(yī)學(xué)與臨床;2017年02期

3 李延峰;;帕金森病的診斷和治療進展[J];中國神經(jīng)免疫學(xué)和神經(jīng)病學(xué)雜志;2017年01期

4 樊開陽;朱麗娜;張文利;張海瑞;張瑜;馬莉;;MPTP誘導(dǎo)小鼠帕金森病亞急性模型和慢性模型的比較[J];中國老年學(xué)雜志;2017年01期

5 秦朝暉;陳彪;顧朱勤;丁暉;胡洪濤;;帕金森病患者疲勞與睡眠障礙的研究[J];中風(fēng)與神經(jīng)疾病雜志;2016年05期

6 王安亮;;帕金森病的早期診斷及臨床治療體會[J];中國現(xiàn)代藥物應(yīng)用;2016年03期

7 張浩;管世鶴;楊凱;葉s，

本文編號：1488223