| Objectives To observe the diurnal time change of the onset of acute gouty arthritis(AGA).On this basis,the temporal therapeutics and possible mechanism of bee venom injection on AGA rat animal model were further explored to provide experimental basis for clinical drug selection.Methods 1 One hundred patients with acute gouty arthritis were included.There were 98 males and 2 females,age(37.05±17.83years),course of disease(1 day to 16 years).Initial onset of 15 cases,recurrence of 85 cases.The day and night time and related information of acute gout attack of all subjects were recorded:(1)According to the theory of Yin and Yang in Traditional Chinese medicine and the theory of four minutes in a day,the time of the latest acute attack of gout is divided into the early part of the morning and the early part of the afternoon and the late part of the night;(2)erythrocyte sedimentation rate,blood uric acid,urine p H,kidney function,blood lipid,etc.2 Sixty-four SD rats were selected,and the light and shade were(L:D=12:12).After 1 week of adaptation,they were randomly divided into bee venom 8AM treatment group,bee venom 8PM treatment group,colchicine 8AM group,colchicine 8PM group,model 8AM group,model 8PM group,blank 8AM group and blank 8PM group.Colchicine group was given 0.8mg/kg·d intragastric administration,blank group and model group were given equal volume of normal saline intragastric administration,once a day,for consecutive7 days.The subcutaneous dose of bee venom was 0.25mg/ mouse,one hour before modeling,once a day for 3 consecutive days.On the 5th day,the model of acute gout arthritis was established by injecting sodium urate into the ankle joints of rats in each group 1h after the last administration.Blank group was injected with equal volume of normal saline into ankle joint.Toe volume measuring instrument was used to measure the toe volume of rats before modeling and 1h,4h,8h,24 h and 48 h after modeling,respectively,and the swelling rate of ankle joint was calculated.The rats were sacrificed 48 h after modeling and blood was taken from abdominal aorta,the contents of IL-6,TNF-α and IL-1β in serum were determined by ELISA.SPSS21.0 statistical software was used for data statistical processing.Results 1 According to the time period divided into four hours a day,the acute gout attack time distribution of 100 patients with gout was 17 patients(17%)in the morning,18patients(18%)in the afternoon,20 patients(20%)in the early night,and 45 patients(45%)in the late night,acute gout attacks peak in the late middle of the night;according to the time period of Yin and Yang,acute gout attacks at night were more than during the day,and the incidence of acute gout attacks at night accounted for 65%.2 The results of linear regression showed that there was no difference between different time periods of acute gout attack and age,erythrocyte sedimentation rate(ESR),urea,serum creatinine,triglyceride,high-density lipoprotein,urine PH,etc(P > 0.05).However,there were differences in uric acid level,cholesterol level and low density lipoprotein level with patients.The specific manifestations were as follows: the uric acid level after night was higher than that in the afternoon(P < 0.05),there was no difference in uric acid level between morning and afternoon(P > 0.05);cholesterol levels and LDL levels were higher in the morning than in the afternoon(P < 0.05),the cholesterol level and low density lipoprotein level in the late night were higher than those in the afternoon(P < 0.05),there was no difference in cholesterol level and LDL level between the night before and the afternoon(P > 0.05).According to the analysis of Yin and Yang day and night time,the day and night attack time was correlated with the change of blood uric acid level(P<0.05),the blood uric acid level was higher at night.3 Experimental study showed that there was no difference in ankle swelling rate among all groups at 1h after modeling.Compared with blank group,the joint swelling degree of colchicine group and bee venom group was significantly higher in model group(P < 0.01),but bee venom treatment group and colchicine treatment group was significantly lower than model group(P < 0.01).Fortyeight hours after modeling,serum levels of TNF-α,IL-6 and IL-1β in bee venom treatment group and colchicine treatment group were significantly lower than those in model group(P < 0.01).4 The ankle swelling rate of 8PM group was significantly lower than that of8 AM group after 4h and 48 h modeling(P < 0.01);The ankle swelling rate of 8PM group was lower than that of 8AM group after 8h and 24 h modeling(P <0 05).The levels of TNF-α and IL-6 were significantly different between 8AM and 8PM treatment groups(P<0 05),the levels of TNF-α and IL-6 were lower in the 8PM treatment group;TNF-α levels of colchicine 8AM group and colchicine 8PM group were different(P < 0.01),TNF-α level was significantly decreased in colchicine 8PM treatment group.There was no significant difference in serum IL-1β level between 8AM group and 8PM group(P > 0.05),and there were no significant differences in serum IL-1β and IL-6 levels between colchicine 8AM group and colchicine 8PM group(P > 0.05).Conclusions 1 Patients with acute gout arthritis have more attacks at night,and most of them are in the late night.This diurnal change is independent of age,course of disease,renal function,lipid level,erythrocyte sedimentation rate and other risk factors,but the blood uric acid level is higher in patients with acute gout arthritis at night.2 Bee venom for injection has obvious prevention and treatment effect on AGA in rats,and can inhibit ankle swelling degree of model rats,and reduce the levels of serum pro-inflammatory cytokines IL-1β,IL-6 and TNF-α.Moreover,the effects of bee venom injection on AGA rats showed diural-day changes,and the effect of bee venom 8PM treatment group was better than that of bee venom 8AM treatment group.The results suggest that night injection of bee venom may improve its efficacy in the prevention and treatment of gout,which is worthy of further study.Figure4;Table12;Reference 121... |
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