The relationship between the levels of NHR, NLR and NHR in PD patients and the course and severity of disease was discussed. The main findings are as follows:(1) NHR and NLR were significantly correlated with PD. (2) With the progression of disease, NHR level decreased significantly. The more advanced PD patients are, the more NHR and MHR are, while there is no significant difference between NLR onset cycle and Hoehn-Yahr classification.(3) ROC curve analysis showed that AUC of NLR was greater than NHR (4) In Spearman analysis,and NHR was negatively correlated with disease course.Based on the above results, we speculated that NLR has a higher predictive value for PD,while NHR may be associated with chronic inflammation in PD patients.
Previous studies have shown that neutrophils have a strong ability to pass through any blood vessel wall and epithelial cells,recruit,activate, and regulate the transport of different leukocyte populations in tissues,and promote the body's inflammatory response through the mutual regulation of chemokines expressed and released by the body[14–15].Our study showed that the level of neutrophils was significantly higher than that of the healthy control group, which also confirmed its promoting effect on the onset of PD to some extent.Not only the relationship between inflammation and PD disease and progression has been mentioned[4–6],moreover,PD has a strong correlation with abnormal lipid metabolism.However,the relationship between the level of HDL-C in peripheral blood and PD has not been determined.Compared with the control group, plasma HDL-C decreased significantly[17–18] or was irrelevant[6,19−20].This study found that HDL-C increased gradually with the extension of PD duration,which was consistent with previous studies.The reasons for consideration are as follows:(1)Smoking has been proved to be negatively correlated with the prevalence rate of PD,and the decrease of smoking rate in PD patients may lead to the decrease of cardiovascular disease.At the same time, one study found that smokers had lower HDL-C levels(2)Levodopa is the standard therapy for Parkinson's disease.Studies have reported that levodopa can reduce blood lipid level,but with the increasing course of the disease,it is often necessary to reduce the dose of levodopa to avoid motor complications.Other reports have shown that PD patients have a cardiometabolic protective effect(3)Other reports have shown that PD patients have a cardiometabolic protective effect,while HDL-C has been recognized as a protective factor for cardiovascular disease, it is not difficult to understand that HDL-C levels rise during the course of the disease.Neutrophils were "closely related" to HDL-C.HDL-C can not only inhibit the expression of neutrophil active activators (PMA and fMLP),but also inhibit its activation,adhesion, diffusion and migration.This is consistent with the findings of this study that neutrophils show a downward trend with the increase of disease course.Certainly, a meta-analysis shows that non-steroidal anti-inflammatory drugs (NSAIDs) are effective in the prevention and treatment of PD patients, and may also lead to decrease of neutrophils.Interestingly,the study concluded that HDL-C levels were significantly lower in patients with advanced PD than in patients with earlier stages.HDL-C plays an important role in the brain under both physiological and pathological conditions. Treatment with enhanced HDL-C function is beneficial to both the peripheral and central nervous systems.ApoA1 exists in cerebrospinal fluid and is the most important structural protein component of HDL-C. Recent studies have reported that higher ApoA1 level can effectively delay the dopaminergic neurodegeneration in PD patients,thus reducing the severity of the disease.Therefore, it is particularly important to pay attention to HDL-C in PD patients.
Infiltrating adaptive immune cells play an important role in neuroinflammatory diseases and neurodegenerative diseases.The formation of Louis nucleosome is a characteristic pathological change in PD patients, which is mainly composed of -synuclein (-SYn). In an animal experiment, T cell infiltration (e.g.,CD3+, CD4+T cells) was detected in the neocortex, hippocampus, and striatum perivascular and parenchyma of -SYN mice.Immunoregulatory mediators and/or lack of effective mechanisms of dissolution led to a pro-inflammatory environment. In addition, T cell interaction with glial cells further enhanced inflammatory activity[5, 28].The results of this study indicated that the lymphocyte level in peripheral blood was significantly lower than that of the control group,which was considered to be related to the recruitment of lymphocytes into the brain parenchyma,leading to the imbalance of lymphocytes and the reduction of CD3+ and CD4+ lymphocyte subsets in PD patients,especially CD3+,which was the most abundant type of lymphocytes.
In conclusion, it is not difficult to conclude that immune inflammatory reaction and dyslipidemia are important factors to promote the occurrence and progression of PD.NHR and NLR were determined by the ratio of neutrophils to HDL-C and neutrophils to lymphocytes, respectively,so it was speculated that the two indexes were related to PD.They are not only simple and fast,but also integrate the information between factors. Compared with a single indicator, they have advantages and reflect the complementary relationship between different pathways, so as to more accurately reflect the inflammatory changes of PD.Therefore,NHR and NLR were considered to be closely related to inflammatory activities and lipid changes.Previous studies have reported that the interaction between increased neutrophils and decreased HDL-C leads to increased NHR level and increased risk of acute myocardial infarction in the elderly.In an analysis of NHR and prognosis after intravenous thrombolysis in acute ischemic stroke,With the aggravation of nerve injury,NHR level gradually increased,and 25% of patients with high NHR level developed severe neurological impairment.PD is a chronic degenerative disease, with the greatest neurological burden between 80 and 89 years old .Our results showed that NHR decreased significantly with the progression of the disease, and NHR increased with the advanced stage of PD.NHR is negatively correlated with course of disease and can be an effective predictor of long-term clinical outcomes.NLR has been widely studied, except for being reported as an inflammatory marker for cardiovascular and cerebrovascular diseases and tumors[31–33],NLR is also associated with PD, but not with different clinical subtypes,considering that dopamine replacement therapy can change the state of peripheral inflammation through its metabolites, other reports have shown that NLR is positively correlated with the increase of homocysteine caused by the decomposition of levodopa[6,34−35].Our study showed that NHR and NLR were closely correlated in terms of influencing the incidence and prediction of PD, but the latter was better. In conclusion, it is suggested that the comprehensive application of NHR and NLR in different stages of PD patients can help improve the diagnosis,treatment and prognosis of PD patients in subsequent clinical work.
However,there are still some limitations in the research process.Firstly, due to retrospective analysis, the effect of NHR and NLR levels on the prognosis of PD patients was limited.Secondly, the sample size involved is relatively small and comes from the same hospital, which makes the results lack of universality.Finally, the specific influence mechanism of NHR and NLR on the occurrence and development of PD is still unknown,and more studies are needed to improve it.