OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METH...OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METHODS:One hundred rats were treated with saline[normal control(NC)group]or complete Freund’s adjuvant(CFA)by right plantar injection for the RA model group,and the latter were randomly divided into 4 groups.Tripterygium wilfordii polyglycoside tablets(雷公藤多苷片,TPT)have anti-inflammatory and are widely used in the clinical treatment of RA,therefore serving as a positive control group.Three days post injection rats were given TPT tablet(TPT group),acupuncture therapy(APT group),and moxibustion treatment(MOX group)for 15 consecutive days,while NC group and model group were equally grasped and fixed and received normal saline.Rat joint swelling scores and arthritis index(AI)were evaluated in each group before the CFA challenge,therapy and after receiving therapy.Myocardial ultrastructure was observed by electron microscope.Enzyme-linked immunosorbent assay was used to detect cardiac troponin I(cTnI)levels in rat myocardial tissue.Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-βsignaling molecules including TGF-β1,Smad2,Smad3,Smad4,and Smad7.Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer.RESULTS:Compared with model group,RA model rats receiving TPT,acupuncture,or moxibustion therapy all showed reduced joint swelling scores and AI(all P<0.01)and improved myocardial damage,whereas rats treated with moxibustion were found to be more marked.Consistently,the expressions of cTnI,TGF-β1,Smad2,Smad3,and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT,APT and MOX group when compared with model group,while the levels of Smad7 showed the opposite result(all P<0.01).Moreover,the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate,dihydroxyacetone phosphate,arachidonic acid,etc was defined and implicated in amino acid,glucose,and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis.CONCLUSION:Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions.The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.展开更多
基金National Natural Science Foundation of China:a Metabolomic Study of the Effects of Moxibustion on Cardiac Function and Its Intervention in RA Model Rats Based on the TGF-β1/Smads Signaling Pathway (No.81403484)Anhui Province University Natural Science Fund Project of China:Exploring the Mechanism of Action of Moxibustion in AA Rats Based on Intestinal Flora and TLR4/NF-KB Signaling Pathway (No.KJ2019A0448)+2 种基金National Project Cultivation Fund Project Plan:Exploring the Mechanism of Action of Moxibustion in AA Rats Based on Intestinal Flora and TLR4/NF-KB Signaling Pathway (No.2019py01)Anhui Province Clinical Medical Research Center [Anhui Provincial Science and Technology Department Anhui Social Science (2020) No.41]the training Program of Outstanding talents in Colleges and Universities:2021 Domestic Visiting Training Program for Outstanding Young Key Teachers in Colleges and Universities (No.gxgnfx2021122)
文摘OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METHODS:One hundred rats were treated with saline[normal control(NC)group]or complete Freund’s adjuvant(CFA)by right plantar injection for the RA model group,and the latter were randomly divided into 4 groups.Tripterygium wilfordii polyglycoside tablets(雷公藤多苷片,TPT)have anti-inflammatory and are widely used in the clinical treatment of RA,therefore serving as a positive control group.Three days post injection rats were given TPT tablet(TPT group),acupuncture therapy(APT group),and moxibustion treatment(MOX group)for 15 consecutive days,while NC group and model group were equally grasped and fixed and received normal saline.Rat joint swelling scores and arthritis index(AI)were evaluated in each group before the CFA challenge,therapy and after receiving therapy.Myocardial ultrastructure was observed by electron microscope.Enzyme-linked immunosorbent assay was used to detect cardiac troponin I(cTnI)levels in rat myocardial tissue.Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-βsignaling molecules including TGF-β1,Smad2,Smad3,Smad4,and Smad7.Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer.RESULTS:Compared with model group,RA model rats receiving TPT,acupuncture,or moxibustion therapy all showed reduced joint swelling scores and AI(all P<0.01)and improved myocardial damage,whereas rats treated with moxibustion were found to be more marked.Consistently,the expressions of cTnI,TGF-β1,Smad2,Smad3,and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT,APT and MOX group when compared with model group,while the levels of Smad7 showed the opposite result(all P<0.01).Moreover,the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate,dihydroxyacetone phosphate,arachidonic acid,etc was defined and implicated in amino acid,glucose,and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis.CONCLUSION:Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions.The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.
