Study On The Characteristics Of TCM Syndromes And The Regulating Effect Of TCM Compounds In Parkinson's Disease Autonomic Nerve Damage

OBJECTIVE:To observe the frequency and clinical characteristics of autonomic dysfunction in Parkinson’s disease(PD);to summarize the characteristics of traditional Chinese medicine(TCM)syndromes of PD autonomic dysfunction.To analyze the correlation between PD autonomic dysfunction,TCM syndrome,and disease progression.To explore the effect of Bushenpinggan(tonifying the kidney and smoothing the liver)decoction on the expression of autonomic pathway proteins in A53T-α-synuclein transgenic rats.METHODS:Study 1 systematically reviewed observational studies on PD autonomic dysfunction in PubMed,EmBase,Cochrane Library,CNKI,Wanfang,and VIP databases.After screening literature,extracting data and evaluating the risk of bias in the included studies,Meta-analysis was performed to calculate the frequency of dysautonomic symptoms,and clinical evaluation methods were summarized.Study 2 was a cross-sectional study.Clinical data of 191 PD participants from Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital,Beijing Hospital,and Peking University Third Hospital were collected.Specific items evaluating autonomic function included:the scales for outcomes in Parkinson’s disease-autonomic(SCOPA-AUT),non-motor symptoms scale(NMSS),hyperhidrosis disease severity scale(HDSS),13-item pattern element scale for Parkinson’s disease(PD-PES-13),orthostatic blood pressure and heart rate measurement,ultrasonography of residual urine measurement,ultrasonography of the vagus nerve.By observing clinical manifestations,we analyzed its characteristic change with the progression of the disease and summarized relevant TCM syndrome.Study 3:A prospective study was conducted.88 participants were followed every 6 months after baseline,and there were altogether 2 follow-ups.The following information was recorded at baseline,6-month,and 12-month:antiparkinsonism medication,whether falls occurred,and SCOPA-AUT score.The medication was converted into levodopa equivalent dose(LED),whose increase was used to evaluate disease progression.And then the correlations between disease progression and TCM syndrome,autonomic function were analyzed.Study 4:A53T-α-synuclein transgenic rats were randomly divided into model group,TCM group and integrated Chinese and Western medicine(ICWM)group.They were given distilled water,Bushenpinggan decoction,and Bushenpinggan decoction combined with Madopar respectively.Normal control group rats were given distilled water.Defecation situation of rats was observed,and expression of acetylcholine transferase(ChAT)and Dopamine beta Hydroxylase(DβH)in the substantia nigra,striatum,and intestines was quantitatively analyzed by immunohistochemistry(IHC)staining.RESULTS:1.From 8716 original studies,98 items(29,011 subjects)were selected.Meta-analysis showed that the manifestations of autonomic dysfunction in PD were defecation and urination disorder.The most frequent symptom was nocturia(59.3%),followed by constipation(56.1%),urgent urination(49.4%),and frequent urination(43.4%),etc.2.The cross-sectional study showed that the frequency of symptoms of autonomic dysfunction in descending order was nocturia(85.3%),constipation(77.5%),hyperhidrosis(57.6%),urgent urination(49.7%),dripping(44.5%),frequent urination(39.8%),etc.The digestive system(r=0.307,P=0.000),the urinary system(r=0.309,P=0.000)and the thermoregulation(r=0.258,P=0.000)autonomic function scores were positively correlated with Hoehn&Yahr stage.The TCM syndrome analysis showed that yin deficiency(B=0.071,P=0.011),qi deficiency(B=0.107,P=0.047)syndrome element scores were positively correlated with the circulatory system autonomic function scores;yin deficiency(B=0.596,P=0.000)syndrome element scores were positively correlated with the digestive system autonomic function scores;kidney deficiency(B=0.747,P=0.000)syndromes element scores were positively correlated with the urinary system autonomic function scores;qi deficiency(B=0.228,P=0.000),yin deficiency(B=0.180,P=0.000)syndrome element scores were positively correlated with the thermoregulatory function scores.3.The follow-up study indicated that LED increased 27.46±82.56 mg,and 14 subjects(15.9%)reported fall events;at the 12th month,LED increased 67.70±118.09 mg,and 18 subjects(20.5%)reported fall events.Yang hyperactivity(OR=3.333,95%CI:1.083-10.262)and spleen deficiency(OR=2.600,95%CI:1.059-6.383)were risk factors for the increase of LED at the end of follow-up.The increase in LED at the end of follow-up was positively correlated with the baseline NMSS-2(B=4.453,P=0.015)score.During the follow-up period,the SCOPA-AUT score did not change significantly compared with the baseline,indicating that the autonomic symptoms were relatively stable.4.The pharmacological study showed that compared with the model group,the normal control group(P=0.039),the TCM group(P=0.037),and the ICWM group(P=0.049)had higher defecation volume.The IHC test found that the expression level of ChAT protein in the substantia nigra,the small intestine,and the colon of the normal control group were higher than that of the model group(P=0.001,P=0.001,P=0.008);the expression level of ChAT protein in the colon of TCM group was higher than that of the model group(P=0.045);the expression level of ChAT protein in the small intestine of the ICWM group was higher than that of the model group(P=0.045).CONCLUSIONS:1.The most common symptoms of autonomic dysfunction in PD are nocturia and constipation.This trend has been confirmed in the clinical research.Except for the circulatory system,the severity of other autonomic system symptoms rises with the increase of Hoehn&Yahr stage.2.The core syndromes of PD autonomic dy sfunction are yin deficiency,qi deficiency,and kidney deficiency;the 1-year follow-up found that yang hyperactivity and spleen deficiency are the key syndromes related to disease progression.3.Bushenpinggan decoction may improve the bowel function of A53T-α-synuclein transgenic rats and increase the expression of ChAT in the intestines.The mechanism remains to be further studied.