Relationship Between Plasma Exosomes MiR-105-5p And MiR-221-3p And Parkinson’s Disease

Background and Objective:Parkinson’s disease(PD)is a common neurodegenerative disease.The diagnosis of PD is mainly based on the clinical manifestations and imaging examinations.Both of the examination criteria are subjective and lack of sensitivity.The formation of Lewis bodies in brain tissue contributes to the diagnosis of PD,but it can not be implemented in clinic because of the difficulty in obtaining brain tissues.Therefore,people need to find new biomarkers.Many studies have confirmed that micro RNAs play a key role in the development of neurodegenerative diseases,and exosomes contain a variety of proteins and genetic materials(micro RNAs,lnc RNAs,circ RNAs),and exist in a wide range of body fluids.Uch as serum,urine,saliva,ascites,amniotic fluid,milk and the like,is convenient to obtain,and the exosomes have low immunogenicity,are not easy to be cleared by the organism,are small in diameter,and are double-layer lipid vesicle structures,so that the carried miRNAs can be ensured to pass through the blood-brain barrier to play a role in cerebrospinal fluid.Recent studies have found that miR-105-5p and miR-221-3p play an important role in the pathogenesis of PD.In order to further verify this study,we detected the expression levels of miR-105-5p and miR-221-3p in plasma exosomes of PD patients.The potential role of miR-105-5p and miR-221-3p as biomarkers in the diagnosis of PD was discussed,and the relationship miRNA105-5p and Movement symptoms of PD,PD with rapid eye movement sleep behavior disorder(RBD)and PD with dementia was analyzed.Methods:A total of 121 plasma samples from sporadic PD patients and 92 plasma samples from healthy examination people were collected in Qingda Affiliated Hospital.The collected experimental specimens were separated from plasma exosome,and the plasma exosomes were extracted.Observe the morphology of exocrine body through transmission electron microscope,Western blot(WB)was used to determine the specific marker proteins CD63 and CD9 in the exocrine body.A new secretory particle size analyzer(q Nano)was used to record the diameter range of the particles.After it was confirmed to be a secretory body,its miRNAs were subjected to reverse transcription,real-time fluorescence quantitative polymerase chain reaction(q RT-PCR).All PD patients were scored according to the Unified Parkinson’s disease rating scale(UPDRS),the Modified Hoehn-Yehr(H&Y)rating scale,the Mini-mental State Examination(MMSE),and the Rapid Eye Movement Sleep Behavior Disorder Screening Scale(RBDSQ).Movement symptoms were divided into tremor-dominant group(TD),bradykinesia with slowness and impaired rigidity(BSID),and postural instability and gait difficulty(PIGD).According to the non-motor symptoms were divided into PD-dementia group and PD-non-dementia group(according to the MMSE score scale),PD-RBD group and PD-non-RBD group.By analyzing the relative expression levels of miR-105-5p and miR-221-3p in the plasma exocrine body,draw the receiver operating curve(ROC)curve of the subject to determine whether there is a correlation with PD motor symptoms,PD with dementia or RBD.Results:(1)Compared with the healthy control group,the level of plasma exosomal miR-105-5p in the PD group(1.81±1.80)was higher than that in the control group(1.25±1.01),and the expression was down-regulated,and the difference was statistically significant(t =2.16,P<0.05);The expression level of plasma exosomes miR-221-3p in PD(1.97±1.68)was higher than that in healthy control group(1.71±1.75),and the difference was not statistically significant(t =0.75,P > 0.05).(2)miR-105-5p(AUC = 0.655,95% CI = 0.618-0.633,P< 0.05),miR-221-3p(AUC= 0.575,95% CI = 0.481-0.668,P< 0.05),The sensitivity and specificity were 73.6% and59.3% for miR-105-5p and 38.3% and 79.7% for miR-221-3p,respectively.(3)The relative expression levels of plasma exosome miRNA-105-5p was not statistically significant in the exercise group(P > 0.05).(4)The expression level of plasma exosomes miR-105-5p in PD-dementia group(2.362±2.228)was higher than that in PD-non-dementia group(2.070±2.097),the difference was not statistically significant(P > 0.05).(5)The expression of plasma exosomes miR-105-5p in PD-RBD group(1.751±1.780)was significantly lower than that in PD-non-RBD group(1.881±1.805),the difference was not statistically significant(P > 0.05).Conclusion:(1)The expression level of miR-105-5p in plasma exocrine is correlated with PD,and the expression is significantly up-regulated than that of healthy people,which may be a biomarker for diagnosis of PD.The expression level of miR-221-3p in plasma secretion was up-regulated in PD,and the difference was not significantly correlated.(2)The expression levels of miR-105-5p in plasma exosomes was not significantly correlated with motor symptom and non-motor symptoms such as PD with dementia or RBD.