艾灸对佐剂性关节炎模型大鼠心功能及TGF-β_1/Smads信号通路的影响

Effect of Moxibustion on Cardiac Function and TGF-β_1/Smads Signaling Pathway in Adjuvant Arthritis Model Rats

目的探讨艾灸对弗氏完全佐剂(CFA)诱导的佐剂性关节炎(AA)模型大鼠的疗效及对心功能、TGF-β_1/Smads信号通路的影响。方法 80只大鼠随机分成正常对照组、模型对照组、雷公藤多苷片(TPT)组和艾灸组,每组20只。采用CFA造模,造模成功后正常组和模型组均不做任何处理,TPT组按体重给予TPT混悬液8 mg/kg灌胃,1次/日;艾灸组予以艾灸足三里、肾俞穴治疗,1次/日,每次20 min。共治疗15日。致炎前1天、治疗前、治疗后检测各组大鼠关节肿胀率、关节炎指数(AI)及心功能[包括左室收缩末压(LVESP)、左室舒张末压(LEVDP)、左室心压上升下降最大速率(±dp/dtmax)、心率(HR)];观察各组大鼠TGF-β_1、Smad2、Smad3、Smad4、Smad7 mRNA及蛋白表达。结果治疗前,与正常组比较,模型组大鼠关节肿胀率及AI明显增高(P<0.01)。治疗后,与正常组比较,模型组关节肿胀率及AI明显增高(P<0.01);模型组±dp/dtmax值、Smad7 mRNA及蛋白表达降低(P<0.01),HR、LVSDP、LVEDP水平及TGF-β_1、Smad2、Smad3、Smad4 mRNA及蛋白表达升高(P<0.05,P<0.01)。与模型组比较,TPT组及艾灸组关节肿胀率及AI明显减低(P<0.01);dp/dtmax值、Smad7 mRNA及蛋白表达升高,而HR、LVSDP、LVEDP水平及TGF-β_1、Smad2、Smad3、Smad4 mRNA及蛋白表达降低(P<0.05,P<0.01);与艾灸组比较,TPT组AI明显升高,LVSP值、-dp/dtmax值及Smad7 mRNA及蛋白表达降低,Smad2、Smad3、Smad4 mRNA表达升高(P<0.05,P<0.01)。结论艾灸在降低CFA诱导AA模型大鼠的关节肿胀度、AI及改善心功能方面明显优于TPT,其机制可能与其调控TGF-β_1/Smads信号通路相关。

Objective To investigate the efficacy of moxibustion on complete Freund＇s adjuvant（ CFA） induced adjuvant arthritis（ AA） rat model and the effect on cardiac function and TGF-β1/Smads signaling pathway. Methods Totally 80 rats were randomly divided into normal control group,model group,tripterygium wilfordii polyglycoside tablet（ TPT） group and moxibustion group,20 rats in each group. The AA rat model was established by CFA injection. While the rats of the normal control group and model control group were untreated. TPT suspension（ 8 mg/kg） was administered to rats in the TPT group once a day according to the weight,while moxibustion group rats were given moxibustion therapy,once a day,20 min for each time. The course of treatment was 15 days. The joint swelling rate,arthritrs index（ AI） and cardiac funtion [including left ventricular end-systolic pressure（ LVESP）,left ventricular end-dias tolic pressure（ LVEDP）,the maximum change rate of left ventricular pressure rise and fall（-dp/dtmax） and heart rate（ HR） ]were measured on the day before inflamed,before and afterthe treatment. The mRNA and protein expression of TGF-β,Smad2,Smad3,Smad4,Smad7 were detected. Results Before the treatment,compared with the normal control group,the joint swelling rate and AI of rats in the model control group were significantly increased（P〈0. 01）. After the treatment,compared with the normal control group,the joint swelling rate and AI of rats in the model control group were significantly increased（P〈0. 01）,the model control group rats＇ ± dp/dtmax and the mRNA and protein expression of Smad7 were significantly reduced,while HR,LVSDP,LVEDP and the mRNA and protein expression of TGF-β1,Smad2,Smad3,Smad4 were significantly increased（P〈0. 05,P〈0. 01）. Compared with the model control group,the joint swelling rate and AI of rats in other groups were decreased significantly（P〈0. 01）,± dp/dtmax and the mRNA and protein expression of Smad7 in other groups were significantly increased,while HR,LVSDP,LVEDP and the mRNA and protein expression of TGF-β1,Smad2,Smad3,Smad4 were decreased（P〈0. 05,P〈0. 01）. Compared with the moxibustion group,the joint swelling rate and AI of rats in the TPT group were significantly increased; LVSP,-dp/dtmax and the protein expression of Smad7 in TPT group were significantly decreased,while the mRNA expression of TGF-β1,Smad2,Smad3 and Smad4 were significantly increased（P〈0. 05,P〈0. 01）. Conclusion Moxibustion could better improve the joint swelling rate,AI and cardiac function of CFA induced AA model rats than TPT,which may contribute to its effect in regulating the cardiac TGF-β1/Smads signaling pathway.