不同预后尖锐湿疣组织中TLR3及TLR9的表达研究

发布时间：2018-06-23 04:55

本文选题：尖锐湿疣 + Toll样受体　；参考：《中国医科大学》2010年硕士论文

【摘要】： 研究背景尖锐湿疣(Condyloma Acuminatum, CA)是主要由感染人乳头瘤病毒(Human Papilloma Virus, HPV)引起人生殖器部位及附近表皮的一种良性乳头瘤样增生性疾病,典型病理改变是表皮中上层出现空泡细胞。CA治疗并不困难,但由于复发率很高,且发病率逐年上升而逐渐引起人们的重视。目前普遍认为,CA的发生、转归与机体免疫功能变化有关。CA患者机体免疫系统受抑制,尤其是细胞免疫功能低下是HPV进入机体后长期持续大量复制的主要原因。 Toll样受体(Toll-like receptor, TLR)是新近发现的一类模式识别受体,广泛分布于细胞表面参与病原微生物及其产物的识别,并通过诱导活性氧中间产物和活性氮中间产物的产生、前炎症因子的释放实现病原微生物的清除和机体免疫状态的调节。它们不仅在天然免疫中起重要作用,同时也被视为天然免疫与获得性免疫的连接点,影响获得性免疫。Toll样受体在CA发病机理中的作用已受到了越来越多的关注。在已发现的11种TLR家族成员中,TLR3和TLR9被认为是抗病毒免疫的重要受体之一。本研究通过观察不同预后CA患者皮损局部TLR3和TLR9的表达情况,试图从一个新的角度反映CA患者机体免疫状态,以期找到更好的治疗方式有效清除HPV,改善CA预后。目的通过观察不同预后CA患者皮损局部TLR3和TLR9的表达情况,探讨TLR3和TLR9在CA发病机制中的作用以及它们与CA发生、发展的关系。方法选择CA患者24例(其中无复发者14例,复发者10例)及正常对照者10例,应用免疫组化法及RT-PCR法分别检测各组CA组织和正常对照包皮组织中TLR3、TLR9的表达情况。所有数据以x±s表示,采用SPSS13.0统计软件进行数据分析,两组间比较采用独立样本t检验,P0.05具有统计学意义。结果 1、免疫组化定位分析：TLR3、TLR9蛋白定位于角质形成细胞的胞浆和(或)胞膜。对照组TLR3、TLR9于表皮全层呈中等强度或弱表达；无复发组TLR3、TLR9于表皮全层强阳性表达,以棘层、颗粒层为主；复发组TLR3、TLR9于表皮全层中等强度表达,以基底层、棘层为主。 2、RT-PCR半定量分析：无复发组TLR3、TLR9 mRNA与对照组相比表达升高(P0.01；P0.05),且无复发组TLR3的表达明显高于TLR9 (P0.05);复发组TLR3、TLR9与对照组相比无明显差异(二者均P0.05),与无复发组相比TLR3减少显著(P0.05)。结论 1、TLR3与TLR9在无复发组CA皮损局部表达上调； 2、TLR3与TLR9在复发组CA皮损局部的表达与对照组相比无显著性差异(P0.05),较无复发组的表达有不同程度减少,其中TLR3减少有显著性差异(P0.05)； 3、TLR3与TLR9的表达部位在无复发CA与复发CA组织中存在差异； 4、TLR3与TLR9的表达部位和表达量的改变可能与CA预后有关,且TLR3的影响可能更大。
[Abstract]:Background Condyloma acuminatum (CA) is a benign papillomatous disease mainly caused by human papilloma virus (HPV). The typical pathological change is that it is not difficult to treat the vacuole cells in the upper and middle epidermis, but the recurrence rate is very high, and the incidence rate is increasing year by year, so people pay more and more attention to it. At present, it is generally believed that the occurrence and outcome of CA is related to the changes of immune function of the body. The immune system of patients with CA is suppressed. In particular, the low cellular immune function is the main cause of HPV replication. Toll-like receptor (TLR) is a new type of pattern recognition receptor. It is widely distributed on the surface of the cells involved in the recognition of pathogenic microorganisms and their products, and by inducing the production of reactive oxygen species intermediate products and active nitrogen intermediates, the release of proinflammatory factors can achieve the clearance of pathogenic microorganisms and the regulation of the immune state of the organism. They not only play an important role in innate immunity, but also are regarded as the junction point between innate immunity and acquired immunity. The role of .Toll-like receptors in CA pathogenesis has been paid more and more attention. TLR3 and TLR9 are considered as one of the important antiviral immune receptors among 11 TLR family members. In this study, we observed the expression of TLR3 and TLR9 in lesions of CA patients with different prognosis, and tried to reflect the immune status of CA patients from a new perspective, in order to find a better treatment to effectively remove HPVand improve the prognosis of CA. Objective to investigate the role of TLR3 and TLR9 in the pathogenesis of CA by observing the expression of TLR3 and TLR9 in lesions of CA patients with different prognosis. Methods 24 cases of CA (14 cases without recurrence, 10 cases of recurrence) and 10 cases of normal control were selected. The expression of TLR3 and TLR9 in CA tissues and normal prepuce tissues were detected by immunohistochemistry and RT-PCR respectively. All the data were expressed as x 卤s and analyzed by SPSS 13.0 statistical software. The comparison between the two groups was statistically significant by using independent sample t-test (P0.05). Results 1. Immunohistochemistry analysis showed that the protein of TLR3 and TLR9 was located in cytoplasm and / or membrane of keratinocytes. In the control group, TLR3 + TLR9 was moderately or weakly expressed in the whole epidermis, TLR3 + TLR9 was strongly expressed in the whole epidermis, mainly in the spinous layer and granular layer, and TLR3 + TLR9 was expressed in the basal layer in the whole epidermis, and TLR3 + TLR9 was expressed in the basal layer of the epidermis. 2Semi-quantitative analysis by RT-PCR: the expression of TLR3nTLR9 mRNA in non-recurrence group was higher than that in control group (P0.01). The expression of TLR3 in non-recurrence group was significantly higher than that in TLR9 group (P0.05), but the expression of TLR3 in relapsing group was not significantly different from that in control group (P0.05), and the expression of TLR3 in non-recurrence group was significantly lower than that in non-recurrence group (P0.05). Conclusion 1the expression of TLR3 and TLR9 in CA lesions without recurrence was up-regulated; 2the expression of TLR3 and TLR9 in recurrent CA lesions was not significantly different from that in control group (P0.05), but the expression of TLR3 was lower than that of non-recurrence group (P0.05). 3There were differences between the expression sites of TLR3 and TLR9 between recurrent CA and non-recurrent CA, and the changes of expression and expression of TLR3 and TLR9 might be related to the prognosis of CA, and the effect of TLR3 might be more significant.
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R752.53

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