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The Role Of Cytokines In Motor Neuron Disease

Posted on:2017-06-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:J YanFull Text:PDF
GTID:1314330515993348Subject:Neurology
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Background and purpose:MND(motor neuron disease)is a disease of unknown etiology,selective loss of motor neurons in cerebral cortex,brainstem and ventricornu.In recent years,the research on inflammatory and immune mechanism in motor neuron disease has received more and more attention,previous research has found that cytokines play different roles in different aspects of immune inflammatory mechanism.In view of this,the expression level in human plasma of Gal-3(galectin 3 binding protein),ZAG(zinc alpha-2 glycoprotein),IL-9(interleukin-9),FKN(fractalkine),TGF(transforming growth factor alpha)was systematically studied in this dissertation.Generally speaking,we investigated the possible role of these cytokines in different aspects of immune inflammatory mechanism in motor neuron disease,preliminarily study the pathological mechanism of immune inflammation in motor neuron disease,explored whether or not someone could be used as a potential biomarker and try to find new possible treatment methods for motor neuron disease.Methods:The plasma levels of Gal-3 and ZAG were measured by ELISA method.The plasma levels of IL-9,FKN,TGF-were measured by MILLIPLEX MAP liquid chip technology.With these indexes of motor neuron disease,statistical analysis was carried on the duration of disease,site of onset,severity of illness and gender respectively,and the relationship between patients and normal controls was systematically studied.Results:(1)The plasma level of Gal-3 in patients was not significantly different compared with normal controls(p=0.05).Further analysis showed that:compared with normal controls,the level in patients with disease duration>12 months increased significantly(p<0.05),the level in patients with disease duration<12 months was not significantly different(p>0.05),the level in patients with disease duration>12 months increased significantly compared to that in patients with disease duration<12 months(p<0.05);compared to normal controls,the level in patients with limb onset increased significantly(p<0.05),the level in patients with bulbar onset was not significantly different(p>0.05),the level in patients with limb onset disease duration>12 months increased significantly compared to that in patients with limb onset disease duration<12 months(p<0.05);compared with normal control,the level in female patients increased significantly(p<0.05),the level in male patients was not significantly different(p>0.05);compared with normal control,the level in patients with ALSFRS-R score>24 points or with ALSFRS-R score<24 points was not significantly different(p>0.05);In addition,the level of Gal-3 was positively correlated with disease duration(RRho=0.293,p=0.037).(2)The plasma level of ZAG in patients increased significantly compared with normal controls(p<0.05).Further analysis showed that:compared with normal controls,the levels in patients of different gender,disease duration,site of onset,severity of disease increased significantly(p<0.05),but were not significantly different in anyone of them(p>0.05);In addition,the level of ZAG in patients was not correlated with disease duration(p>0.05).(3)The plasma level of IL-9 in patients decreased significantly compared with normal controls(p<0.05).Further analysis showed that:compared with normal controls,the levels in patients of different gender,disease duration,site of onset,severity of disease decreased significantly(p<0.05),but were not significantly different in anyone of them(p>0.05);In addition,the level of IL-9 in patients was not correlated with disease duration(p>0.05).(4)The plasma level of FKN in patients decreased significantly compared with normal controls(p<0.05).Further analysis showed that:compared with normal controls,the levels in patients of different gender,disease duration,site of onset,severity of disease decreased significantly(p<0.05),but were not significantly different in anyone of them(p>0.05),except that the level in patients with disease duration>12 months increased significantly compared to that in patients with disease duration<12 months(p<0.05);In addition,the level of FKN in patients was not correlated with disease duration(p>0.05).(5)The plasma level of TGF-a in patients increased significantly compared with normal controls(p<0.05).Further analysis showed that:compared with normal controls,the levels in patients of different gender,disease duration,site of onset,severity of disease increased significantly(p<0.05),but were not significantly different in anyone of them(p>0.05),except that the level in patients with disease duration>12 months increased significantly compared to that in patients with disease duration ?12 months(p<0.05);In addition,the level of TGF-? in patients was positively correlated with disease duration(RRho=0.287,p=0.041).Conclusion:(1)The plasma Gal-3 in patients may be a potential biological marker of disease,may play a protective role,and could help clinicians assess the progress of motor neuron disease and potential therapeutic targets;(2)The significantly increased plasma ZAG level in patients compared with normal controls confirmed that a high metabolic state could exist in patients with motor neuron disease,which provides a theoretical basis for dietary intervention.Meanwhile this indicator may play an anti-inflammatory effect,which is yet to be confirmed by further studies however.(3)The plasma IL-9 level in patients decreased significantly compared with normal controls,however the specific mechanism needs further study;(4)The plasma FKN levels in patients decreased significantly compared with normal controls,however the specific mechanism needs further study;(5)The plasma TGF-? level in patients may play an important role in the pathogenesis of motor neuron disease.The research of epidermal growth factor receptor inhibitors could be an important step to explore new potential methods for treatment of motor neuron disease.
Keywords/Search Tags:motor neuron disease, amyotrophic lateral sclerosis, Gal-3, ZAG, IL-9, Fractalkine, TGF-?
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