梅毒血清固定與梅毒螺旋體tpr基因亞型關(guān)系的初步研究
發(fā)布時間：2018-12-31 20:18
【摘要】：研究背景 梅毒是由梅毒螺旋體(蒼白螺旋體,treponema pallidum,TP)引起的一種性傳播疾病(sexually transmitted diseases,STD),主要通過性接觸傳播,也可以通過胎盤、產(chǎn)道、輸血等途徑傳播。梅毒的廣泛流行和傳播已成為世界各國嚴重的公共衛(wèi)生問題。近年來我國梅毒發(fā)病人數(shù)快速增長,成為影響人民群眾健康和社會穩(wěn)定的重要問題。梅毒除可侵犯生殖器官和皮膚粘膜外,尚可侵犯骨關(guān)節(jié)、眼、中樞神經(jīng)系統(tǒng)和心血管系統(tǒng)等幾乎全身各組織器官,嚴重的可致殘甚至致命。梅毒還可以通過胎盤垂直傳播感染胎兒,造成死產(chǎn)、早產(chǎn)或新生兒先天性梅毒,危害下一代的健康。梅毒的傳播方式和易感因素與艾滋病(acquired immune deficiency syndrome,AIDS)有許多相似之處,增加了患者對人類免疫缺陷病毒(human immunodeficiency virus,HIV)的易感性,一般認為梅毒發(fā)病率的上升預示了AIDS傳播蔓延的危險性增加,所以梅毒的防治是早期預防控制AIDS蔓延的重點環(huán)節(jié)。 人體感染梅毒后產(chǎn)生兩種抗體,即非特異性反應素抗體和特異性抗螺旋體抗體,血清反應素抗體陰轉(zhuǎn)是評價梅毒是否治愈的關(guān)鍵指標。梅毒患者確診后按正規(guī)驅(qū)梅方案治療,大部分患者可以達到臨床治愈和血清治愈的效果。在臨床上有部分患者經(jīng)治療后雖然臨床癥狀完全消失,但非特異性反應素抗體試驗持續(xù)陽性,不能轉(zhuǎn)陰,即為梅毒血清固定(sero-resistance)。梅毒血清固定是臨床上梅毒治療的難題,其形成原因目前仍不清楚。 TP的致病機制、分子毒理機制以及機體對TP的免疫反應等方面尚有許多未明了之處。20世紀90年代末,美國疾病控制與防治中心(Center for Disease Control and Prevention,CDC)的Pillay等發(fā)現(xiàn)不同TP臨床菌株間存在arp(acidic repeat protein)和tpr(treponema pallidum repeat)基因的差異,首次對TP進行基因分型。近年來國外學者對TP tpr基因進行了更進一步的研究,Lorenzo等認為TP tpr基因是引起梅毒的主要的致病因子,是宿主體液免疫的主要靶基因,這些基因可能在梅毒感染的免疫反應和保護性免疫反應中起著重要作用,國外學者發(fā)現(xiàn)不同的TP tpr亞基因可引發(fā)不同的抗體反應和免疫反應。但迄今為止尚未見有關(guān)梅毒血清固定與TP分子亞型關(guān)系方面的研究報道,血清固定的形成是否與TP tpr基因亞型相關(guān),值得進一步研究。 采用巢式PCR技術(shù)從分子水平探討廣州地區(qū)TP tpr基因亞型分布及其與梅毒血清固定的相關(guān)性,預期結(jié)果可為梅毒的分子流行病學研究提供理論依據(jù),對從分子水平闡明梅毒的發(fā)病機制有較大幫助,可解決臨床上的難題,對控制梅毒和艾滋病的傳播有重要意義。 研究目的 研究廣州地區(qū)TP tpr基因亞型分布情況,初步探討梅毒血清固定與TP tpr基因亞型的關(guān)系,為血清固定的形成機制和梅毒的預防治療及分子流行病學研究提供理論依據(jù)。 研究對象和方法 收集廣州地區(qū)確診為早期梅毒且未經(jīng)治療的初診患者標本102份,其中全血75份,潰瘍分泌物27份,用巢式PCR擴增TP基礎膜蛋白基因(basic membrane protein gene,bmp),陽性者再應用巢式PCR擴增TP tpr基因,通過限制性內(nèi)切酶Mse I酶切后用限制性片段長度多態(tài)性方法(RFLP)對TP菌株進行tpr基因分型;所有早期梅毒患者均按衛(wèi)生部的標準,規(guī)范驅(qū)梅治療,記錄并追蹤治療前及治療后第3個月、第6個月、第9個月及第12個月時患者血清TRUST滴度變化,在第12個月時判定患者否形成血清固定,分析TP tpr基因亞型與患者血清固定的關(guān)系。 研究結(jié)果 102例入選病例,16例失訪,剔除失訪病例,86例(86/102)有效病例標本中,巢式PCR篩選TP bmp基因陽性者48份(55.8%),血清TRUST初始滴度不同的患者組間TP bmp基因擴增陽性率差異經(jīng)雙側(cè)Fisher’s exact test無統(tǒng)計學意義(P=0.24)。成功進行TP tpr基因分型者40份,分出3個TP tpr基因亞型,其中d亞型28份,e亞型4份,i亞型8份;規(guī)范驅(qū)梅治療后12個月,有33例(33/40)患者血清TRUST轉(zhuǎn)陰,其中25例為d亞型、4例為i亞型及4例e亞型,7例(7/40)患者血清固定,包括3例d亞型、4例i亞型。i亞型血清固定的發(fā)生率最高。不同的tpr基因亞型與患者血清固定形成與否的差異經(jīng)雙側(cè)Fisher’s exact test有統(tǒng)計學意義(P=0.04)。 結(jié)論 TP tpr基因的d亞型是廣州地區(qū)TP的優(yōu)勢流行株(70%)。i亞型TP感染者形成血清固定的例數(shù)較多,梅毒血清固定的形成可能與TP tpr基因亞型的差異相關(guān)。
[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%).
【學位授予單位】：廣州醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R759.1
本文編號：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%).
【學位授予單位】：廣州醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R759.1
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相關(guān)期刊論文 前3條
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2 曾鐵兵,吳移謀,黃澍杰,吳志周;衡陽和江門地區(qū)梅毒螺旋體基因分型的初步研究[J];中華皮膚科雜志;2004年12期
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