摘要
目的:通过研究清热利湿化浊法对湿热痹阻型慢性痛风性关节炎患者的临床疗效及NOD结构域样受体3(NLRP3)/白细胞介素-1β(IL-1β)信号通路的影响,初步探讨其作用机制。方法:采用随机数字表法将纳入的60例湿热痹阻证慢性痛风性关节炎患者分为2组,观察组和对照组各30例;同时设健康组30例。对照组给予口服非布司他治疗;观察组在对照组的基础上联合加味四妙散治疗,治疗周期为4周。分别记录患者一般临床资料、中医证候积分、血清尿酸(UA)、血肌酐(SCr)、尿素氮(BUN)、空腹血糖(FPG)、低密度脂蛋白(LDL)、甘油三酯(TG)、总胆固醇(TC)、红细胞沉降率(ESR)、C反应蛋白(CRP)水平,采用酶联免疫吸附测定法(ELISA)检测IL-1β、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平,采用蛋白质免疫印迹法(Western blot)检测NLRP3、胱天蛋白酶-1(Caspase-1)、凋亡相关斑点样蛋白(ASC)水平。结果:与健康组比较,2组患者治疗前体质量指数(BMI)、收缩压(SBP)、舒张压(DBP)、UA、SCr、BUN、FPG、LDL、TG、TC水平均明显升高(P<0.05,P<0.01),HDL水平明显降低(P<0.05)。2组患者治疗前IL-1β、TNF-α和IL-6水平均显著升高(P<0.01)。与本组治疗前比较,2组患者关节疼痛,关节压痛,关节肿胀,关节发热,活动障碍,身困倦怠,黏腻口苦,小便黄赤,舌象积分均明显降低,差异具有统计学意义(P<0.05,P<0.01)。与对照组治疗后比较,观察组患者关节发热,身困倦怠,黏腻口苦,大便黏滞,小便黄赤,舌象,脉象积分均明显降低(P<0.05)。观察组总有效率为80.0%(24/30),对照组总有效率为56.7%(17/30),观察组总有效率明显高于对照组,差异具有统计学意义(χ^(2)=11.916,P<0.05)。与本组治疗前比较,2组患者BMI、SBP、DBP、UA、SCr、BUN、FPG、LDL、TG、TC、ESR、CRP、IL-1β、TNF-α、IL-6水平及VAS评分均明显降低(P<0.05,P<0.01);与对照组治疗后比较,观察组患者BMI、ESR、IL-1β水平及VAS评分均明显降低(P<0.05)。Western blot结果显示,与健康组比较,2组患者治疗前外周血淋巴细胞(PBMCs)中的NLRP3、Caspase-1、ASC的蛋白表达均显著升高(P<0.01)。与本组治疗前比较,治疗后2组患者PBMCs中的NLRP3、Caspase-1、ASC的蛋白表达均明显降低(P<0.05,P<0.01)。与对照组治疗后比较,观察组患者NLRP3、Caspase-1表达水平均明显降低(P<0.05)。结论:清热利湿化浊法可有效改善湿热痹阻型慢性痛风性关节炎的临床症状并减轻炎症反应,且有较好的安全性;其机制可能与抑制NLRP3/IL-1β信号通路信号通路有关。
Objective:To 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.Method:Sixty 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.Enzymelinked 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.Result:Before 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(χ^(2)=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-1βlevels,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).Conclusion:The Qingre Lishi Huazhuo method can effectively improve the clinical symptoms and reduce inflammation of chronic gouty arthritis of dampnessheat obstruction syndrome with good safety.The mechanism may be related to the inhibition of the NLRP3/IL-1βsignaling pathway.
作者
杜明瑞
赵哲
李华燕
王鑫
崔炎
DU Mingrui;ZHAO Zhe;LI Huayan;WANG Xin;CUI Yan(The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2023年第11期133-140,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
河南省中医药科学研究专项(2018ZY2060)
河南省中医药科学研究专项(2021JDZY083)
河南省中医药传承与创新人才工程(仲景工程)中医药学科拔尖人才项目(CZ0237-15)。
