| Objective: Neuromyelitis optica spectrum disorders(NMOSD) is an immune-mediated inflammatory/demyelinating disease central nervous system syndrome with a predilection for optic nerve and spinal cord. The course is progressive or remission relapse. The exact etiology and pathogenesis is not clear. At present, it is considered that there may be infection, heredity, environment, immunity, oxidative stress and other factors to cause the pathogenesis of the disease. Lipoic acid(LA) is a kind of natural antioxidant, which has been found not only powerful antioxidant effect, but also found play an important role in neuroprotection and immune regulation. The objective of this study is to further understand whether lipoic acid exerts anti-inflammatory or anti oxidative effects in the treatment of NMOSD. Through randomized controlled study, we observed the indexes(peripheral blood CD19~+B cell percentage, oxidative stress indexes MDA, SOD and immune regulation related indicators IF-6, IF-10, IF-4 and TNF-?) dynamic changes of three treatment groups(criterion group, LA group and AZA group) patients with NMOSD in the acute and remission stage. We investigate the oxidative stress status and immune status in different periods of disease. With azathioprine as positive control group, to explore the mechanism of lipoic acid in the development of the disease and treatment process. Thus, it can provide a new direction for the clinical treatment of the disease.Methods: In this study, we collected patients which was diagnosed as NMO or NMOSD according to the 2012 NMO diagnosis and treatment of the Chinese Expert Consensus from January 1, 2015 to September 30, 2015 in the Second Hospital of Hebei Medical University, Department of Neurology, outpatient and inpatient. These 45 patients were randomly divided into three groups and followed up for 1 months. 1) Criterion group: Patients is given methylprednisolone 500 mg intravenously once a day and then three days halved until 75 mg. And then changed to oral prednisone acetate tablets, reduced gradually. 2) LA group: Patients were given hormone usage as criterion group. At the same time, given lipoic acid 0.6g intravenously daily(a total of 14 days), and then oral lipoic acid soft capsule 0.6g once a day. 3) AZA group: Treatment as criterion group. Patients were given oral hormone the same time given oral azathioprine 100 mg once a day. Review blood routine and liver function timely. The day of drawing blood in hospital is as the 0 day. All of the patients were extracted venous blood on the 0 day, 14 th day and 30 th day respectively. The venous blood was inspected by flow cytometry analysis to detect the percentage of CD19~+B cells and the serum was saved to refrigerate. At the same time we give the patients with EDSS score. After collection,all the serum was detected by kit to test the content of oxidative stress indexes MDA, SOD and immune regulation related indicators IF-6, IF-10, IF-4 and TNF-?.Results:1 The basic information of every groups of patients: there is no statistical difference among three groups of patients in the constituent ratio of age and sex.2 Nerve function loss score: In the study, with the time of the extension, the EDSS score of the LA group decreased, and the difference had statistically significant(P<0.05). The EDSS score of LA group and AZA group patients was significantly lower than that of the criterion group decreased in 30 th days. The difference was statistically significant(P<0.05).3 The percentage of peripheral blood B cellsAccording to the second hospital of Hebei Medical University, Blood Department of internal medicine laboratory quality control standard, the normal reference value of the percentage of peripheral blood CD19~+B cells is 12%. There was significant statistically difference between three groups in 0 day and 14 th day with normal reference values(P<0.05). Compeared with normal reference values, the percentage of peripheral blood CD19~+B cells in 0 day and 14 th day of the three groups were increased. In the 30 th day, compared with the normal reference value, criterion group and LA group is still increased. The difference was significant. The difference between AZA group and the normal reference value was not statistically significant. And AZA group has been restored to the normal range basically.The percentage of peripheral blood CD19~+B cell between the three groups has difference significantly in the 14 th day(P>0.05). With the extension of time, the percentage of peripheral blood CD19~+B cells in each groups were decreased in 30 th days, especially AZA group. It was significantly lower than that of the other two groups. And the differences had statistically significant(P<0.05).4 Serological Indicators4.1 IL-10 contentAlong with the extension of disease, the level of IL-10 showed an upward trend within each group, and the differences have statistical significance(P<0.05). This showed that the increased IL-10 play a positive role in the recovery period of the disease.The contents of IL-10 in three groups have no statistical significance(P>0.05) in 14 th days. The result of the 30 th day was same as the 14 th day(P>0.05). Compared with the other groups, the level of IL-10 was significantly increased in LA group, which indicated that the anti-inflammatory effect of lipoic acid was prominent.4.2 TNF-a contentWith the extension of the duration of the disease, the level of TNF-? showed a downward trend in each group(P<0.05), indicating that the TNF-? has had a negative impact in the recovery period of the disease. The level of TNF-? among the three groups compared no significant difference in the 14 th day(P>0.05). Compared LA group, AZA group was significantly lower(P<0.05) in the 30 th days.4.3 MDA contentWith the extension of the disease duration, the variation tendency of the level has significant difference in each group. With the remission stage of disease the level of MDA in LA group, there was a clear downward trend(P<0.05). It showed that lipoic acid plays an antioxidant stress role in the period of disease remission stage. The level of MDA among the three groups compared no significant difference in the 14 th day(P>0.05) and the 30 th day(P>0.05).4.4 SOD content:The change of the SOD level in each group was not consistent. The level of SOD in LA group was increased with the remission stage of disease, and there was a significant upward trend(P<0.05). It showed that lipoic acid plays an antioxidant stress role in the period of disease treatment. With the course of disease, the level of SOD among the three groups compared no significant difference in the 14 th day(P>0.05)and the 30 th day(P>0.05).Conclusions:1 The higher level of CD19~+B cells percentage in NMOSD patients further proves that the humoral immune is the main pathogenesis of NMOSD at acute stage.2 In this experiment, we observed the change of the inflammatory cytokine IF-10 and TNF-?, which indicates that the anti-inflammatory effect of lipoic acid was obvious in the treatment of NMOSD.3 During the remission stage, the content of MDA decreased and the content of SOD increased. It showed that the lipoic acid had a certain therapeutic effect on NMOSD, which could be improved the oxidative stress state of the patients.4 Through this experiment we observed that LA can reduce the EDSS score. It is speculated that LA may be through anti-inflammatory, anti oxidative stress and so on to comprehensive treatment NMOSD. |
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