Expression And Significance Of ResovinD1 In Peripheral Blood Of Patients With Amyotrophic Lateral Sclerosis

Objective:The purpose of this study was to evaluate the level of plasma inflammatory dissipation factor Resolvin D1（Rv D1）in patients with amyotrophic lateral sclerosis（ALS）,and to explore the correlation between Rv D1 and ALS related clinical indicators as well as its correlation with plasma inflammatory cytokines,so as to explore the role of Rv D1 in the progression of ALS,and provide new ideas for the treatment and diagnosis of ALS.Method:1.Forty patients with sporadic ALS who were diagnosed or treated in outpatient and inpatient departments of neurology of our hospital from December 2020 to December 2021 were included in this study.General basic information of patients（including gender,time from onset to diagnosis age,site of onset,body mass index,ALSFRS-R score,etc.）was registered,and serum samples were collected.In addition,23 healthy patients with matched age and gender were recruited as the healthy control group,and their basic information was recorded.2.The concentration of Rv D1 in plasma of ALS patients and control group was determined by enzyme-Linked immunosorbent assay（ELISA）.CBA were used to measure the levels of relevant cytokines IL-2,IL-4,IL-6,IL-10,IFN-γ,TNF-α and IL-17 A in serum.Some patients underwent skeletal muscle biopsy.Result:1.A total of 63 qualified researchers were enrolled in this study,including 40 sporadic ALS cases（28 males and 12 females）in the patient group,with a male to female ratio of 2.33:1 and an average age of57.15±10.54 years.There were 23 healthy controls（13 males and 10females）with an average age of 56.19±9.21 years.Compared with the control group,the level of plasma Rv D1 in patient group [43.94（30.79,55.34）pg/ml] was lower than that in control group [83.52（38.81,118.49）pg/ml],and the difference was statistically significant（P<0.05）.2.The patient group was subgroup analyzed according to the onset site,and the results showed that the plasma Rv D1 levels of ALS patients with upper limb,lower limb and bulb onset were statistically significant（P<0.05）.There was no significant difference in plasma Rv D1 level between upper and lower limb onset patients（P>0.05）.3.The plasma levels of inflammatory cytokines IL-2,IL-4,IL-6,IL-10,IFN-γ,TNF-α and IL-17 A in ALS patients were compared with those in control group.The results showed that plasma levels of cytokines TNF-α and IL-6 in ALS patients were higher than those in control group（P <0.05;P < 0.001）,IL-17 A and IL-10 were lower than those in control group（P < 0.05;P < 0.01）.4.Correlation analysis was conducted between plasma Rv D1 level and general clinical characteristics（age,body mass index,disease progression rate,ALSFRS-R score,respiratory score and disease duration）.The results showed that there was a negative correlation between plasma Rv D1 concentration and disease progression rate（r =-0.4788,P<0.01）.There was no significant correlation between Rv D1 level and age,body mass index,ALSFRS-R score,respiratory score and duration of disease（P>0.05）.5.The correlation analysis between Rv D1 and plasma inflammatory factors IL-2,IL-4,IL-6,IL-10,IFN-γ,TNF-α and IL-17 A showed no significant correlation between plasma Rv D1 and these inflammatory factors（P>0.05）6.Correlation analysis was conducted between plasma Rv D1 and lipid metabolism in ALS patients,and the results showed that lipid drop deposition and broken red fiber were found in skeletal muscle fibers of some patients,while the plasma Rv D1 level of these patients was lower than that of ALS patients without lipid drop deposition.Conclusion:（1）The level of plasma inflammatory dissipation factor Rv D1 in ALS patients was lower than that in control group,suggesting that ALS patients had inflammatory dissipation disorder.（2）The plasma levels of pro-inflammatory cytokines IL-6 and TNF-α increased,while the levels of anti-inflammatory cytokines IL-10 decreased,suggesting that the peripheral immune system of ALS patients may be transformed to pro-inflammatory cytokines mediated immune response.（3）The plasma Rv D1 level of ALS patients was negatively correlated with DPR,but had no significant correlation with ALSFRS-R score.Plasma Rv D1 is a protective factor.（4）The plasma level of Rv D1 was lower in ALS patients with skeletal muscle pathology and lipid deposition,suggesting that Rv D1 may regulate lipid metabolism.（5）Plasma Rv D1 may be used as an indicator of the dissipation of peripheral inflammatory response in ALS,and may be a new biomarker of ALS due to its neuroprotective effect.