几种细胞因子血清水平及其基因多态性与结核病相关性研究

发布时间：2018-06-16 21:03

本文选题：结核病患者 + TNF-α　；参考：《青海大学》2013年硕士论文

【摘要】：目的：通过观察肿瘤坏死因子-a(tumor necrosis factor-a,TNF-a)、γ-干扰素(interferon-γ,IFN-γ)及白细胞介素-4(interleukin-4,IL-4)在不同结核病患者和健康对照者外周血清中表达的变化和规律，分析结核的发生、发展及预后与TNF-a、IFN-γ、IL-4的关系；通过测定IL-4T590C和TNF-a G308A的基因多态性分析其与青海藏族结核病易感性的关系。方法：采用酶联免疫吸附试验（ELSIA）测定25例活动性结核病患者、25例非活动性初治结核患者、25例抗结核治疗3月患者、25例健康对照者外周血清TNF-α、IL-4、IFN-γ水平；以聚合酶链-限制性片段长度多态法(PCR—RFLP)对25例藏族结核病患者、25例健康非藏族对照者的IL-4T590C和TNF-α G308A基因多态性分析,并进行方差分析和组内两两比较的SNK分析。本研究病例来源于青海省传染病医院门诊和住院确诊病例，健康对照者来自于相同医院同期体检的健康正常人群25例；结果：活动性结核病患者、非活动性初治结核患者、抗结核治疗3月患者、健康对照组血清TNF-α分别为0.156±0.070ng/ml、0.082±0.031ng/ml、0.106±0.019ng/ml、(0.058±0.012)ng/ml，经结核组内两两比较及与健康对照者比较，差异均有统计学意义(P0.05)；活动性结核病患者、初治非活动性结核患者、抗结核治疗3月患者IFN-γ为(0.008±0.002)ng/ml、(0.103±0.016)ng/ml、(0.152±0.038)ng/ml,健康对照组为(0.042±0.020)ng/ml，经结核组内两两比较及与健康对照者比较，差异均有统计学意义(P0.05)；活动性结核病患者、初治非活动性结核患者、抗结核治疗3月组患者IL-4为(0.150±0.047)ng/ml、(0.074±0.023)ng/ml、(0.028±0.013)ng/ml,健康对照组为(0.025±0.008)ng/ml；与健康对照者比较，除抗结核治疗3月组的IL-4的差异无统计学意义外，活动性结核组和初治非活动性结核组IL-4含量均有差异，差异均有统计学意义(P0.05)，而结核组内两两比较IL-4含量差异均有统计学意义(P0.05)；IL-4T590C TT、CT和CC基因型在对照组中分别是56%、36%和8%，，而在藏族结核患者组中分别是64%、32%和4%。CC基因型在对照组及藏族结核患者组中，相对于TT和CT基因组表达较低，但是对照组和藏族结核患者组间并没有明显差异（P0.05）。经过分析，C和T基因频率在对照组中是0.74和0.26，而在藏族结核患者组中是0.80和0.20，两组之间经过比较，C和T基因频率也无明显差异（P0.05）；TNF-α G308AGG、GA和AA基因型在对照组中分别是64%、28%和8%，而在藏族结核患者组中分别是60%、28%和12%。AA基因型在对照组及结核患者组中，相对于GG和GA基因组表达较低，但是对照组和结核患者组间并没有明显差异（P0.05）。经过分析，G和A基因频率在对照组中是0.78和0.222，而在藏族结核患者组中是0.74和0.26，两组之间经过比较，G和A基因频率也无明显差异（P0.05）基因多态性在藏族结核患者和健康对照者无差异(P＞0.05)；结论：结核病患者外周血清TNF-α、IFN-γ、IL-4的水平与结核病的发生与病情发展相关，因此检测TNF-α、IFN-γ、IL-4对结核病情的发展及预后判断有一定价值；而IL-4T590C和TNF-α G308A基因多态性与青海藏族结核的发生无明显关系，推测IL-4T590C和TNF-α G308A基因多态性与青海藏族结核易感性无关。
[Abstract]:Objective: To observe the changes and regularities of the expression of -a (tumor necrosis factor-A, TNF-a), interferon (interferon- gamma, IFN- gamma) and interleukin -4 (interleukin-4, IL-4) in the peripheral serum of different tuberculosis patients and healthy controls, and to analyze the relationship between the occurrence, development and prognosis of the tuberculosis. The relationship between IL-4T590C and TNF-a G308A gene polymorphisms and susceptibility to tuberculosis in Qinghai was analyzed.
Methods: enzyme-linked immunosorbent assay (ELSIA) was used to determine 25 cases of active tuberculosis, 25 non active primary tuberculosis patients, 25 cases of anti tuberculosis treatment in March, 25 healthy controls, and peripheral serum TNF- alpha, IL-4, IFN- gamma level, and 25 cases of Tibetan tuberculosis patients with polymerase chain restriction fragment length polymorphism (PCR RFLP), 25 The IL-4T590C and TNF- alpha G308A gene polymorphisms of healthy non Tibetan controls were analyzed, and the variance analysis and the SNK analysis of 22 in the group were compared. The cases were derived from the outpatient and hospitalized cases of the infectious disease hospital in Qinghai Province, and the healthy controls were from the normal healthy population of 25 cases in the same hospital in the same hospital.
Results: the serum TNF- alpha was 0.156 + 0.070ng/ml, 0.082 + 0.031ng/ml, 0.106 + 0.019ng/ml and (0.058 + 0.012) ng/ml in the healthy control group. The difference was statistically significant (P0.05) in the tuberculosis group (P0.05). In the patients with non active tuberculosis, IFN- gamma was (0.008 + 0.002) ng/ml, (0.103 + 0.016) ng/ml, (0.152 + 0.038) ng/ml, and healthy control group (0.042 + 0.020) ng/ml. The difference was statistically significant (P0.05) compared with healthy controls (P0.05); active tuberculosis patients, In the early treatment of non active tuberculosis patients, the IL-4 in the anti tuberculosis treatment group was (0.150 + 0.047) ng/ml, (0.074 + 0.023) ng/ml, (0.028 + 0.013) ng/ml, and the healthy control group was (0.025 + 0.008) ng/ml. Compared with the healthy controls, there was no statistical difference between the anti tuberculosis treatment group and the March group, the active tuberculosis group and the initial non active tuberculosis. There were significant differences in IL-4 content in group IL-4, but there were significant differences in IL-4 content in the tuberculosis group (P0.05), IL-4T590C TT, CT and CC genotypes were 56%, 36% and 8% in the control group, while 64%, 32% and 4%.CC in the Tibetan tuberculosis patients were in the control group and the Tibetan tuberculosis patients. In the group, the expression of the genome relative to TT and CT was low, but there was no significant difference between the control group and the Tibetan tuberculosis patients (P0.05). After analysis, the frequency of C and T gene was 0.74 and 0.26 in the control group, but 0.80 and 0.20 in the Tibetan tuberculosis group, and there was no significant difference between the C and T gene frequencies between the two groups (P0.05); TNF- alpha G. 308AGG, GA and AA genotypes were 64%, 28%, and 8% in the control group, while the 60%, 28% and 12%.AA genotypes in the Tibetan tuberculosis group were lower than the GG and GA genomes in the control and tuberculosis patients, but there was no significant difference between the control group and the tuberculosis group (P0.05). The frequencies of G and A genes were analyzed. There were 0.78 and 0.222 in the group, and 0.74 and 0.26 in the Tibetan tuberculosis patients. There was no significant difference in G and A gene frequencies between the two groups. There was no difference between the Tibetan tuberculosis patients and the healthy controls (P > 0.05).
Conclusion: the level of TNF- alpha, IFN- gamma, IL-4 in the peripheral serum of tuberculosis patients is related to the development of tuberculosis and the development of the disease. Therefore, the detection of TNF- alpha, IFN- gamma, IL-4 is of certain value to the development and prognosis of tuberculosis, while IL-4T590C and TNF- alpha G308A gene polymorphism is not related to the occurrence of Tibetan tuberculosis in Qinghai. It is speculated that IL-4T590C and TNF- alpha G308A gene polymorphism is not associated with tuberculosis susceptibility in Qinghai Tibetan population.
【学位授予单位】：青海大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R52

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