| Objective: Neuromyelitis optica spectrum disorders(NMOSD)is a group of immune-mediated diseases in the central nervous system,which is characterized by demyelinating disease.Now,the exact pathogenesis is not clear yet.But the present studies have showed that oxidative stress,the destruction of the blood brain barrier,chemotactic cytokines may take important parts in its process.The traditional treatments have many disadvantages,such as greatly side effect,unaffordable price and limited forms of oral dosage.Lipoicacid(LA)is a kind of powerful and natural antioxidant,which also has been founded play an important role in neuroprotection and anti-inflammation.It has small side effect,and convenient to take.Lipoicacid has been widely used in the treatment of diabetic peripheral neuropathy,and get prominent clinical effect.but the clinical effect remains to be further observed in patients with NMOSD.Our study takes the healthy adults as healthy control(HC)group,patients with NMOSD as case(CA)group.Through randomized controlled study,case group can be divided into standard treatment(ST)group,lipoicacid(LA)group,and azathioprine(AZA)group.According to the expanded disability status scale(EDSS),the patients were divided into mild(0 ~ 3score),moderate(4 ~ 6 score)and severe(> 6 score).In order to understand the state of inflammation and blood-brain barrier(BBB)and explore the mechanism of lipoicacid in the development of the disease to provide new direction for the treatment of NMOSD,we observed the dynamic changes of matrix metalloproteinase-9(MMP-9)and interleukin-17(IL-17)levels in the plasma in different periods of disease and utilized the disability status scale(EDSS).Methods: In this study,we take 60 definite patients as case group,from January 1,2015 to September 30,2016 in the internal medicine department,Surgery clinic department and in-patient department of the Second Hospital of Hebei Medical University,who were diagnosed as NMOSD,according to the 2012 NMO diagnosis and treatment of the Chinese Expert Consensus.As well,we randomly take 50 healthy adults as healthy control group,who take physical examination in the Second Hospital of Hebei Medical University.The 60 patients were randomly divided into three groups: the standard treatment(ST)group,the LA group and the AZA group.The standard treatment group: In acute stage,patients were given methylpre dnisolone sodium succinate for injection 500 mg intravenously once a day for three days,250 mg intravenously once a day for three days,and then 125 mg intravenously once a day for three days.And then changed to oral prednisone acetate tablets 75 mg once a day for 7 days,40 mg once a day for 14 days,20 mg once a day for 14 days,10 mg once a day for 14 days,5mg once a day for 14 days in remittent stage.The LA group: on the basis of the standard treatment group,extra 0.6g lipoicacid injection was added in the intravenous infusion once a day for 14 days in acute stage,and in remission stage extra 0.6g oral lipoicacid capsules were added in once a day for 30 days.AZA group: Treatment was like standard treatment group in acute stage.In remittent stage patients were given oral azathioprine 50 mg once a day as the time oral hormone given.Review the blood routine and liver function.If it was normal,patients were given oral azathioprine 100 mg once a day for 30 days,during which time the blood routine and liver function were reviewed timely.The first day of blood drawing in hospital as the 0 day,all of the patients were taken venous blood for 3ml with an empty belly on the 0 day,14 th day and 30 th day respectively.After collection,we centrifuge the venous blood for 10 minutes and then extract serum at last frozen at-80°C until analyzed.At the same time we marked the patients with EDSS score.we draw a healthy adult 3 ml blood at random,which was treated as the same as the case group.All the serum was tested the content of IL-17、MMP-9 by nzymelinked immuno sorbent assay(ELISE).Results:1The basic information between Case group and Healthy control group: There is no statistical difference between case group and control group in the constituent ratio of age and gender(P >0.05).There are also no statistical difference among the three groups(the ST group,the LA group and the AZA group)of patients in the case group in the constituent ratio of age,gender,and the source of the patients(P >0.05),which are all comparable.2 The comparison of index among the three groups:There is no statisticaldifference among three groups(the ST group,the LA group and the AZAgroup)of patients in the serum level of MMP-9,IL-17 and Disease rating onthe 0th day(P > 0.05),that are comparable.3 The Case group compared with the Healthy control group on the 0th day: the serum levels of MMP-9and IL-17 in the case group was increased compared with the healthy control group,and there were both significant statistically between the two groups(P<0.05).4 The serum levels of MMP–9 comparison: As time goes on,the serum levels of MMP-9 concentration gradually decreased,and the difference was statistically significant(P <0.05),which illustrated that the three treatment regimens can inhibit the expression of MMP-9.Although there was no statistically significant difference among the three groups(P >0.05),compared with the other two groups,the decrease of the MMP-9 in the LA group seems more obvious.5 The serum levels of IL-17 comparison: As time goes on,the serum levels of IL-17 concentration gradually decreased in all groups,and there was significant statistically on each time point within the three groups(P < 0.05).It suggested that after 30 days of treatment,three groups of serum IL-17 levels were significantly decreased.There was no significant difference among the three groups on the 0th day and the 14 th day(P >0.05).By comparison of the 30 th days’ average data,there was statistical significance between the lipoic acid group and the ST group(P<0.05),but there was no statistical difference between the AZA group and the LA group and the ST group(P >0.05).All of these indicated that lipoicacid may inhibit the expression of IL-17.And as time goes by,the anti-inflammatory effect of the lipoicacid seems more obvious.6 The comparison of EDSS score: As time goes on,the EDSS gradually decreased in all groups,and there was significant statistically on each time point within the three groups(P < 0.05).It proved that the three therapies can promote the illness recovery and relieve patients degree of disability.Although there was no statistical difference among the three groups on the 0th day,14 th day and 30 th day,from the declining trend,we can see that the declining trend of the LA group and AZA group were more obvious compared with the the ST group.We believe that the trend would be more and more obvious by enlarging the sample size and extending the time of observation.Conclusions:1 IL-17 and MMP-9 were up-regulated in NMOSD acute stage.The detection of its level has a certain clinical diagnostic value and may serve as a new target for the treatment of NMOSD.2 In this study,it was found that glucocorticoid could inhibit the expression of MMP-9 and IL-17 in NMOSD patients,which may be one of the mechanisms of glucocorticoid in the treatment of NMOSD and accelerate the remission of patients,and provides important evidence for the treatment of NMOSD.3 In this study,by observing the dynamic changes of MMP-9 between the groups,lipoicacid can further protect the blood-brain barrier by inhibiting the expression of MMP-9 expression.Lipoicacid has certain treatment for NMOSD.4 In this study,It suggested that lipoicacid can inhibit the expression of IL-17 to reduce the inflammatory response by observing the dynamic changes of IL-17 between the groups,and As time goes on,the anti-inflammatory effect of the lipoicacid seems more obvious.5 We found that lipoicacid can significantly decrease the EDSS of the patients and reach the same treatment as azathioprine.Due to its non-toxic side effects,we speculate that lipoicacid may become an therapeutic drugs for NMOSD.But the exact pathogenesis remains to be further observed. |
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