Effects of Shengui Jiajian Pills on myocardial fibrosis and TGF-βi/Smads signaling pathway in aged hypothyroid rats
Objective To study the effects of Shengui Jiajian Pills on myocardial fibrosis and the transforming growth factor-β1(TGF-β1)/Smads signaling pathway in elderly rats with hypothyroidism;To preliminarily explore the mechanism of Shengui Jiajian Pills in treating hypothyroid heart disease through the TGF-β1/Smads pathway.Methods Totally 60 SD rats were randomly divided into normal group,model group,sodium levothyroxine group,and Shengui Jiajian Pills low-,medium-,and high-dosage groups,with 10 rats in each group.A model of elderly hypothyroid heart injury in rats was prepared by freely drinking 0.1％propylthiouracil(PTU)for 10 weeks.Each group of rats was gavaged with the corresponding drug once a day for 6 weeks.After the last gastric lavage,an electrocardiogram was performed,hematoxylin-eosin staining(HE)was used to observe pathological changes in the heart tissue;bitter acid-toluidine blue staining was used to detect fibrosis of the heart tissue;TUNEL staining was used to observe myocardial cell apoptosis;Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of thyroid stimulating hormone(TSH),free triiodothyronine(FT3),free thyroxine(FT4)in the serum,as well as brain natriuretic peptide(BNP),creatine kinase isoenzymes MB(CK-MB),and lactate dehydrogenase(LDH);Western blot was used to detect the relative expressions of TGF-β1,p-Smad2,p-Smad3,α-smooth muscle actin(α-SMA),matrix metalloproteinase-1(MMP-1),TIMP1,Bax,and Caspase-3 in the heart tissue;and immunofluorescence was used to detect the positive expressions of TGF-β1,Smad3,α-SMA,and MMP-1 in the heart tissue.Results Compared with the model group,the inflammatory cell infiltration and cell damage in the heart of rats in each dosage group of Shengui Jiajian Pills were improved,the myocardial fibrosis area ratio was significantly reduced(P＜0.05),and the myocardial cell apoptosis rate significantly decreased(P＜0.05),the levels of TSH,BNP,CLD,and HK-MB in serum significantly decreased(P＜0.05).The levels of FT3 and FT4 increased in the Shengui Jiajian Pills medium-and high-dosage groups(P＜0.05),while the positive expressions of TGF-β1,Smad3,α-SMA,and MMP-1 decreased(P＜0.05).The protein expression of TGF-β1,p-Smad3,MMP-1,Bax,and Caspase-3 decreased(P＜0.05),and the expression of TIMP-1 increased(P＜0.05).The expression of Smad7 increased in the Shengui Jiajian Pills medium-dosage group(P＜0.05).Conclusion Shengui Jiajian Pills may reduce myocardial collagen fiber deposition by modulating the TGF-β1/Smad3 signaling pathway,thereby partially reversing the pathological features of hypothyroidism-induced myocardial injury,with more pronounced effects observed in the medium and high dosage groups.
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