| Objective: Tuberculous meningitis(TBM)is a serious infectious disease of the central nervous system with high morbidity and mortality.The main diseased regions of tuberculous meningitis are meningeal and brain parenchyma.At the same time,the spinal cord and spinal meninges may also be involved.About 20%~25% of the patients end up in death,and some of the survivors had neurological sequelae.In terms of the patient’s own factors,TB infection vary from person to person in the same environment,Therefore,host genes are associated with susceptibility to tuberculosis.The researchers found that leukotriene A4 hydrolase(LTA4H)gene polymorphisms associated with the susceptibility of tuberculous meningitis.In the course of the development of the disease,the severity of the disease is related to the patient’s physical condition,bacteria,environment,diagnosis,treatment and so on.The clinical manifestation,severity and prognosis in each patient are not identical,so the inflammatory reaction process plays an important role in the development of the disease.LTA4 H is the key enzyme to convert leukotriene A4(LTA4)into leukotriene B4(LTB4),and LTB4 is a potent proinflammatory cytokine.Lipoxin A4(LXA4)is an anti-inflammatory factor in the metabolic pathway of arachidonic acid.This experiment was to explore different genotype of LTA4 H relation with the severity of tuberculous meningitis,and analysis of the correlation with the the level of LTB4,LXA4 in cerebrospinal fluid and the severity of TBM patients.Methods:1 Collecting TBM patients from January 2014 to October 2016 admitted to the second hospital of Hebei medical university neurology department as the research object.According to the clinical diagnostic criteria of tuberculosis meningitis in 2010 by the international cooperation group of tuberculosis meningitis,the diagnosis group and the probable group of patients were included in the study.According to the British Medical Research Council(MRC)standards,the patients were divided into three stages.2 The DNA in venous blood of patients with tuberculous meningitis was collected and extracted,and then gene sequencing of SNP gene of LTA4 H rs17525495 was detected.3 Collecting cerebrospinal fluid(CSF)within 72 hours after admission from TBM patient before admitted anti tuberculosis treatment,At the same time,CSF after two weeks of regularly anti tuberculosis treatment of and the CSF of patients with non central nervous system infection as the control group respectively.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of LTB4 and LXA4 in CSF.4 SPSS 21.0 statistical software was used for statistical analysis.The distribution of genotype frequencies in patients with TBM was tested by Hardy-Weinberg equilibrium.Lumbar puncture,cerebrospinal fluid leukocyte count and biochemical examination results were compared by chi square test.LTB4 and LXA4 levels in the CSF were reported as median±SD.For statistical data meet the normal distribution and homogeneity of variance,the single factor analysis of variance(one-factor ANOVA)was used to compare among many groups;statistical data were not satisfy normal distribution was reported as(median,four percentile interval)and multiple comparisons with Kruskal-Wallis H test.The test level was 0.05,P<0.05 was accepted as significant difference.Results:1 184 patients with tuberculous meningitis were enrolled in this study,of which there were 137 patients in the diagnosis group,and probable tuberculous meningitis in 47 patients.Male: female was 1.9:1.The mean age of the patients was 39.8±16.7 years old.The main clinical manifestations were headache,fever,nausea and vomiting.2 Hardy-Weinberg equilibrium(Hardy-Weinberg equilibrium,HWE)detection: P>0.05,it conformed to the Hardy-Weinberg equilibrium.Tuberculous patients with LTA4 H gene rs17525495 locus for type CC patients with a total of 91 cases(49.5 percent),75 cases of type CT(49.5percent),18 cases of type TT(9.8 percent).The allele frequency of C was 69.8percent,T was 30.2 percent.3 Comparison of different genotypes of disease severity in patients with clinical manifestations and results of lumbar puncture: Among the patients with type CC,the proportion of patients with stage I was higher than that in stage II and III,P< 0.05.In the patients with type TT,the proportion of patients with stage II and III was higher than that of patients in stage I,P<0.05.The clinical manifestations of the patients with different genotypes were statistically analyzed,including headache,fever,nausea and vomiting,neck stiffness and epilepsy.Compared with the groups,there was no significant difference in the incidence of headache,nausea,vomiting,consciousness disorder and epilepsy between different genotypes.Compared with CC and CT patients,type of TT patients had higher incidence of fever,neck stiffness,P<0.05.It showed that the incidence of fever and neck rigidity in TT patients was higher than that in patients with type CC and type CT.There is no difference between different genotypes of patients with lumbar puncture,chloride,protein,glucose,P > 0.05.4 Comparison of LTB4 and LXA4 levels in the case group and the control group: 33 patients with tuberculous meningitis were included in this study,and the control group was 28 patients.Cases were divided into before treatment group,after treatment group and control group.Comparing the level of LTB4 and LXA4 between the three groups before treatment,before treatment group was the highest while the lowest is the control group.5 The LTB4 and LXA4 levels of the patients in different groups were compared: 13 cases were in stageⅠ,11 were in stageⅡ,9 were in stage 3.The level of LTB4 in CSF in patients with different stages of disease before treatment was compared: P> 0.05,there was no significant difference between the three groups.LXA4 levels in CSF were compared: P<0.05.The results showed that the LXA4 level of patients with stageⅠand Ⅲ was higher than that of the patients in stage Ⅱ,but the LXA4 level between the stageⅠand stage Ⅱwas not statistically different.6 Comparison of LTB4 and LXA4 levels in patients with different genotypes in the case group: Cases of CC genotype of LTA4 H rs17525495was 11,type of CT was 16 and TT was 6.The levels of LTB4 in CSF of the three different genotypes were compared: P<0.05.Through the comparison between the three groups,the level of LTB4 in CSF of patients with type TT was higher than that of type CC patients.Conclusions:1 TBM patients with mild condition with LTA4 H gene for the rs17525495 locus suggesting the CC type;while patients with severe disease showed that the LTA4 H gene rs17525495 locus was TT.2 The levels of LTB4 in CSF of patients with different genotypes of tuberculous meningitis were different.The level of LTB4 in CSF of patients with TT was higher than that in patients with type CC,but there was no correlation between the level of LTB4 and the severity of the disease.3 The levels of LTB4 and LXA4 in cerebrospinal fluid of patients with TBM were higher than those in the control group,and the treatment was higher than that of the control group,suggesting that both of them may be of significance in the evaluation of clinical therapeutic effect in the future. |
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