Mechanism of Qingre Lishi Huazhuo Method（Modified Simiaosan） on Chronic Gouty Arthritis of Dampness-heat Obstruction Syndrome Based on NLRP3/IL-1β Signaling Pathway / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo study the clinical efficacy of the Qingre Lishi Huazhuo method on patients with chronic gouty arthritis of dampness-heat obstruction syndrome and the effect on nucleotide-binding oligomerization domain-like receptor 3（NLRP3）/interleukin-1β （IL-1β） signaling pathway to preliminarily explore its mechanism. MethodSixty patients with chronic gouty arthritis of dampness-heat obstruction syndrome were enrolled and divided into a treatment group （30 cases） and a control group （30 cases） according to the random number table method. Thirty people were assigned to the healthy group. Patients in the control group were treated with oral Febuxostat， while those in the treatment group were treated with modified Simiaosan combined with Febuxostat. Treatment lasted four weeks. The general clinical data， traditional Chinese medicine （TCM） syndrome scores， serum uric acid （UA）， serum creatinine （SCr）， blood urea nitrogen （BUN）， fasting blood glucose （FPG）， low-density lipoprotein （LDL）， triglyceride （TG）， total cholesterol （TC）， erythrocyte sedimentation rate （ESR）， and C-reactive protein （CRP） of patients were recorded. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of IL-1β，TNF-α， and IL-6，and the levels of NLRP3，cysteinyl aspartate-specific protease-1 （Caspase-1）， and apoptosis-associated speck-like protein containing a CARD （ASC） were detected by Western blot. ResultBefore treatment， the levels of body mass index （BMI）， systolic blood pressure （SBP），diastolic blood pressure （DBP），UA，SCr，BUN，FPG，LDL，TG，and TC in both groups significantly increased （P<0.05，P<0.01），and the levels of HDL significantly decreased as compared with those in the healthy group（P<0.05）. Additionally， the levels of IL-1β， TNF-α， and IL-6 in both groups significantly increased before treatment （P<0.01）. Compared with the results before treatment， patients in the two groups had significant reductions in tube pain， joint tenderness， joint swelling，joint fever， activity disorders， body fatigue， sliminess， bitter mouth， yellow and red urine， and tongue manifestation scores （P<0.05，P<0.01）. Compared with patients in the control group after treatment， those in the treatment group had a significant decrease in joint fever， body fatigue， sliminess， bitter mouth，sticky stool，yellow and red urine， tongue manifestation score， and pulse score （P<0.05）. The total effective rate in the treatment group was 80.0% （24/30）， higher than 56.7% （17/30）in the control group（χ2=11.916，P<0.05）. Compared with the results before treatment， BMI， SBP， DBP， UA， SCr， BUN， FPG， LDL， TG， TC， ESR，CRP， IL-1β， TNF-α， IL-6 levels， and VAS score in both groups significantly decreased （P<0.05，P<0.01）. Compared with patients in the control group after treatment， those in the treatment group had decreased DBP，ESR， IL-1β levels， and VAS score （P<0.05）. Western blot results showed that before treatment， the protein expression of NLRP3， Caspase-1， and ASC in peripheral blood mononuclear cells （PBMCs） of patients in both groups were higher than those in the healthy group （P<0.01）. Compared with the results before treatment， the protein expression of NLRP3， Caspase-1， and ASC in PBMCs in patients of both groups after treatment decreased （P<0.05，P<0.01）. Compared with the control group after treatment， the treatment group showed decreased expression levels of NLRP3 and Caspase-1（P<0.05）. ConclusionThe Qingre Lishi Huazhuo method can effectively improve the clinical symptoms and reduce inflammation of chronic gouty arthritis of dampness-heat obstruction syndrome with good safety. The mechanism may be related to the inhibition of the NLRP3/IL-1β signaling pathway.