梅毒血清固定与梅毒螺旋体tpr基因亚型关系的初步研究
发布时间：2018-12-31 20:18
【摘要】：研究背景 梅毒是由梅毒螺旋体(苍白螺旋体,treponema pallidum,TP)引起的一种性传播疾病(sexually transmitted diseases,STD),主要通过性接触传播,也可以通过胎盘、产道、输血等途径传播。梅毒的广泛流行和传播已成为世界各国严重的公共卫生问题。近年来我国梅毒发病人数快速增长,成为影响人民群众健康和社会稳定的重要问题。梅毒除可侵犯生殖器官和皮肤粘膜外,尚可侵犯骨关节、眼、中枢神经系统和心血管系统等几乎全身各组织器官,严重的可致残甚至致命。梅毒还可以通过胎盘垂直传播感染胎儿,造成死产、早产或新生儿先天性梅毒,危害下一代的健康。梅毒的传播方式和易感因素与艾滋病(acquired immune deficiency syndrome,AIDS)有许多相似之处,增加了患者对人类免疫缺陷病毒(human immunodeficiency virus,HIV)的易感性,一般认为梅毒发病率的上升预示了AIDS传播蔓延的危险性增加,所以梅毒的防治是早期预防控制AIDS蔓延的重点环节。 人体感染梅毒后产生两种抗体,即非特异性反应素抗体和特异性抗螺旋体抗体,血清反应素抗体阴转是评价梅毒是否治愈的关键指标。梅毒患者确诊后按正规驱梅方案治疗,大部分患者可以达到临床治愈和血清治愈的效果。在临床上有部分患者经治疗后虽然临床症状完全消失,但非特异性反应素抗体试验持续阳性,不能转阴,即为梅毒血清固定(sero-resistance)。梅毒血清固定是临床上梅毒治疗的难题,其形成原因目前仍不清楚。 TP的致病机制、分子毒理机制以及机体对TP的免疫反应等方面尚有许多未明了之处。20世纪90年代末,美国疾病控制与防治中心(Center for Disease Control and Prevention,CDC)的Pillay等发现不同TP临床菌株间存在arp(acidic repeat protein)和tpr(treponema pallidum repeat)基因的差异,首次对TP进行基因分型。近年来国外学者对TP tpr基因进行了更进一步的研究,Lorenzo等认为TP tpr基因是引起梅毒的主要的致病因子,是宿主体液免疫的主要靶基因,这些基因可能在梅毒感染的免疫反应和保护性免疫反应中起着重要作用,国外学者发现不同的TP tpr亚基因可引发不同的抗体反应和免疫反应。但迄今为止尚未见有关梅毒血清固定与TP分子亚型关系方面的研究报道,血清固定的形成是否与TP tpr基因亚型相关,值得进一步研究。 采用巢式PCR技术从分子水平探讨广州地区TP tpr基因亚型分布及其与梅毒血清固定的相关性,预期结果可为梅毒的分子流行病学研究提供理论依据,对从分子水平阐明梅毒的发病机制有较大帮助,可解决临床上的难题,对控制梅毒和艾滋病的传播有重要意义。 研究目的 研究广州地区TP tpr基因亚型分布情况,初步探讨梅毒血清固定与TP tpr基因亚型的关系,为血清固定的形成机制和梅毒的预防治疗及分子流行病学研究提供理论依据。 研究对象和方法 收集广州地区确诊为早期梅毒且未经治疗的初诊患者标本102份,其中全血75份,溃疡分泌物27份,用巢式PCR扩增TP基础膜蛋白基因(basic membrane protein gene,bmp),阳性者再应用巢式PCR扩增TP tpr基因,通过限制性内切酶Mse I酶切后用限制性片段长度多态性方法(RFLP)对TP菌株进行tpr基因分型;所有早期梅毒患者均按卫生部的标准,规范驱梅治疗,记录并追踪治疗前及治疗后第3个月、第6个月、第9个月及第12个月时患者血清TRUST滴度变化,在第12个月时判定患者否形成血清固定,分析TP tpr基因亚型与患者血清固定的关系。 研究结果 102例入选病例,16例失访,剔除失访病例,86例(86/102)有效病例标本中,巢式PCR筛选TP bmp基因阳性者48份(55.8%),血清TRUST初始滴度不同的患者组间TP bmp基因扩增阳性率差异经双侧Fisher’s exact test无统计学意义(P=0.24)。成功进行TP tpr基因分型者40份,分出3个TP tpr基因亚型,其中d亚型28份,e亚型4份,i亚型8份;规范驱梅治疗后12个月,有33例(33/40)患者血清TRUST转阴,其中25例为d亚型、4例为i亚型及4例e亚型,7例(7/40)患者血清固定,包括3例d亚型、4例i亚型。i亚型血清固定的发生率最高。不同的tpr基因亚型与患者血清固定形成与否的差异经双侧Fisher’s exact test有统计学意义(P=0.04)。 结论 TP tpr基因的d亚型是广州地区TP的优势流行株(70%)。i亚型TP感染者形成血清固定的例数较多,梅毒血清固定的形成可能与TP tpr基因亚型的差异相关。
[Abstract]:Study Background Syphilis is a kind of sexually transmitted disease (STD) caused by Treponema pallidum (Treponema pallidum, TP), which is mainly transmitted through sexual contact, and can also be transmitted via placenta, production line, blood transfusion, etc. The widespread prevalence and spread of syphilis has become a serious public health question in all countries of the world in recent year, that rapid increase of the number of syphilis in our country has become an important question to affect the health and social stability of the people in addition to that organs of the genital organs and the mucous membrane of the skin, the syphilitic can also violate the organs of the whole body, such as the joint, the eye, the central nervous system and the cardiovascular system, Life. Syphilis can also spread through the placenta to infect the fetus, causing death, premature birth or congenital syphilis of the newborn, and the health of the next generation. The way of transmission of syphilis and the susceptibility to AIDS have many similarities, which increases the susceptibility of the patient to human immunodeficiency virus (HIV). It is generally considered that the increase of the incidence of syphilis indicates the risk of the spread of the spread of AIDS. The prevention and control of syphilis is the key ring of early prevention and control of the spread of AIDS. Section. Two kinds of antibodies are produced after the human body is infected with syphilis, that is, the non-specific reactive antibody and the specific anti-helix antibody, and the negative rotation of the serum reactive antibody is the effect of evaluating whether the syphilis is cured or not. Key index. After the diagnosis of the syphilitic patients, the patients can be treated according to the regular meme scheme, and most of the patients can reach the clinical cure and the serum cure. The results showed that, after the treatment, the clinical symptoms disappeared completely, but the non-specific reactive antibody test continued to be positive, which could not be transferred to the negative, i.e., sero-reseran, for syphilis. ce). Syphilis serum fixation is a difficult problem for clinical syphilis treatment, and the cause of its formation is still It is not clear that the pathogenesis of TP, the molecular toxicological mechanism, and the body's immune response to TP are not clear. At the end of the 1990s, the Center for Disease Control and Prevention of the United States Pillay et al. of the ntion, CDC), et al., found that there was an arp (acidic repeat protein) and tpr (treponema pallium repeat) gene in different TP clinical strains, and the first time for TP In recent years, the foreign scholars have further studied the TP tpr gene, Lorenzo and others think that the TP tpr gene is the main pathogenic factor causing the syphilis, which is immune to the host body fluid. The main target genes, these genes may play an important role in the immune response and protective immune response of the syphilis infection, and foreign scholars have found that different TP tpr subgenes can trigger different antibody responses. and immune response, but so far, studies have not been found on the relationship between the serum fixation of the syphilis and the subtypes of TP molecules, and whether the formation of the serum is related to the subtype of the TP tpr gene is worth it. Further study was carried out. The distribution of TP tpr gene and its correlation with the serum of syphilis were discussed from the molecular level by using the nested PCR technique. The expected results can provide a theoretical basis for molecular epidemiological study of syphilis, which can be used to explain the incidence of syphilis from the molecular level. The mechanism has great help, can solve the clinical problems, and can be used for controlling syphilis and AIDS. to spread in order to study the distribution of TP tpr gene in Guangzhou, the relationship between the serum fixation of syphilis and the subtype of TP tpr gene, the mechanism of the formation of serum and the prevention and treatment of syphilis and the molecular flow were discussed. The study of the line of cardiology The basic membrane protein gene of TP (basic membrane protein) was amplified by nested PCR. The Tpr gene was amplified by restriction fragment length polymorphism (RFLP) by restriction fragment length polymorphism (RFLP) by restriction fragment length polymorphism (RFLP), and all early syphilis patients were treated with restriction fragment length polymorphism (RFLP). The changes in serum TRUST drop in patients at the 3-month, 6-, 9-and 12-month period before and after treatment, 6-month, 9-month, and 12-month follow-up to the Ministry of Health, and the determination of the patient to form a serum-based fixation at the end of the 12th month, and the analysis of TP tp r gene The relationship between the type and the serum level of the patient was studied. The results of the study were 102 cases, 16 cases of lost follow-up, the cases of missing follow-up, 86 cases (86/ 102) of the effective case specimens, and the nested PCR was selected by the nested PCR. The difference of the positive rate of TP-bmp gene in the patients with different P-bmp gene was 48 (52.8%) and the difference of the two-sided Fisher's exac in the patients with different initial drop of TRUST. t test was of no statistical significance (P = 0. 24). 40 parts of TP tpr gene type were successfully carried out, and 3 TP tpr gene subtypes were isolated, including 28 parts of d subtypes, 4 parts of e subtype and 8 parts of i subtype. The serum TRUST of the patients (33/ 40) was negative, of which 25 were of type d, 4 were i and 4 e and 7 (7/ 40). the serum of the patient was fixed, including 3 d subtypes, The difference of the different tpr gene subtype with the patient's serum immobilization was the two-sided Fisher's exac. t t Conclusion The d subtype of TP tpr gene is the dominant epidemic strain of TP in Guangzhou area (70%).
【学位授予单位】：广州医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R759.1
本文编号：2397064
[Abstract]:Study Background Syphilis is a kind of sexually transmitted disease (STD) caused by Treponema pallidum (Treponema pallidum, TP), which is mainly transmitted through sexual contact, and can also be transmitted via placenta, production line, blood transfusion, etc. The widespread prevalence and spread of syphilis has become a serious public health question in all countries of the world in recent year, that rapid increase of the number of syphilis in our country has become an important question to affect the health and social stability of the people in addition to that organs of the genital organs and the mucous membrane of the skin, the syphilitic can also violate the organs of the whole body, such as the joint, the eye, the central nervous system and the cardiovascular system, Life. Syphilis can also spread through the placenta to infect the fetus, causing death, premature birth or congenital syphilis of the newborn, and the health of the next generation. The way of transmission of syphilis and the susceptibility to AIDS have many similarities, which increases the susceptibility of the patient to human immunodeficiency virus (HIV). It is generally considered that the increase of the incidence of syphilis indicates the risk of the spread of the spread of AIDS. The prevention and control of syphilis is the key ring of early prevention and control of the spread of AIDS. Section. Two kinds of antibodies are produced after the human body is infected with syphilis, that is, the non-specific reactive antibody and the specific anti-helix antibody, and the negative rotation of the serum reactive antibody is the effect of evaluating whether the syphilis is cured or not. Key index. After the diagnosis of the syphilitic patients, the patients can be treated according to the regular meme scheme, and most of the patients can reach the clinical cure and the serum cure. The results showed that, after the treatment, the clinical symptoms disappeared completely, but the non-specific reactive antibody test continued to be positive, which could not be transferred to the negative, i.e., sero-reseran, for syphilis. ce). Syphilis serum fixation is a difficult problem for clinical syphilis treatment, and the cause of its formation is still It is not clear that the pathogenesis of TP, the molecular toxicological mechanism, and the body's immune response to TP are not clear. At the end of the 1990s, the Center for Disease Control and Prevention of the United States Pillay et al. of the ntion, CDC), et al., found that there was an arp (acidic repeat protein) and tpr (treponema pallium repeat) gene in different TP clinical strains, and the first time for TP In recent years, the foreign scholars have further studied the TP tpr gene, Lorenzo and others think that the TP tpr gene is the main pathogenic factor causing the syphilis, which is immune to the host body fluid. The main target genes, these genes may play an important role in the immune response and protective immune response of the syphilis infection, and foreign scholars have found that different TP tpr subgenes can trigger different antibody responses. and immune response, but so far, studies have not been found on the relationship between the serum fixation of the syphilis and the subtypes of TP molecules, and whether the formation of the serum is related to the subtype of the TP tpr gene is worth it. Further study was carried out. The distribution of TP tpr gene and its correlation with the serum of syphilis were discussed from the molecular level by using the nested PCR technique. The expected results can provide a theoretical basis for molecular epidemiological study of syphilis, which can be used to explain the incidence of syphilis from the molecular level. The mechanism has great help, can solve the clinical problems, and can be used for controlling syphilis and AIDS. to spread in order to study the distribution of TP tpr gene in Guangzhou, the relationship between the serum fixation of syphilis and the subtype of TP tpr gene, the mechanism of the formation of serum and the prevention and treatment of syphilis and the molecular flow were discussed. The study of the line of cardiology The basic membrane protein gene of TP (basic membrane protein) was amplified by nested PCR. The Tpr gene was amplified by restriction fragment length polymorphism (RFLP) by restriction fragment length polymorphism (RFLP) by restriction fragment length polymorphism (RFLP), and all early syphilis patients were treated with restriction fragment length polymorphism (RFLP). The changes in serum TRUST drop in patients at the 3-month, 6-, 9-and 12-month period before and after treatment, 6-month, 9-month, and 12-month follow-up to the Ministry of Health, and the determination of the patient to form a serum-based fixation at the end of the 12th month, and the analysis of TP tp r gene The relationship between the type and the serum level of the patient was studied. The results of the study were 102 cases, 16 cases of lost follow-up, the cases of missing follow-up, 86 cases (86/ 102) of the effective case specimens, and the nested PCR was selected by the nested PCR. The difference of the positive rate of TP-bmp gene in the patients with different P-bmp gene was 48 (52.8%) and the difference of the two-sided Fisher's exac in the patients with different initial drop of TRUST. t test was of no statistical significance (P = 0. 24). 40 parts of TP tpr gene type were successfully carried out, and 3 TP tpr gene subtypes were isolated, including 28 parts of d subtypes, 4 parts of e subtype and 8 parts of i subtype. The serum TRUST of the patients (33/ 40) was negative, of which 25 were of type d, 4 were i and 4 e and 7 (7/ 40). the serum of the patient was fixed, including 3 d subtypes, The difference of the different tpr gene subtype with the patient's serum immobilization was the two-sided Fisher's exac. t t Conclusion The d subtype of TP tpr gene is the dominant epidemic strain of TP in Guangzhou area (70%).
【学位授予单位】：广州医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R759.1
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相关期刊论文 前3条
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