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.

ObjectiveTo investigate the effects of Xixintang （XXT）-medicated serum on the amyloid β-protein （Aβ）_25-35-induced polarization of BV-2 microglial cells by a cell experiment and uncover the potential mechanisms of this formula in the prevention and treatment of Alzheimer's disease （AD）， thus providing scientific evidence for the clinical application of XXT. MethodsBV-2 microglial cells were subcultured. The optimal concentrations of XXT-medicated serum and Aβ_25-35 were determined via the cell-counting kit-8 （CCK-8） assay. The cell experiment was carried out with the following groups： blank control， model （Aβ_25-35 at 40 μmol·L^-1）， XXT-medicated serum （Aβ_25-35 at 40 μmol·L^-1 + 10% XXT-medicated serum）， and blank serum （Aβ_25-35 at 40 μmol·L^-1 + 10% blank serum）. After 24 hours of cell incubation， immunofluorescence was used to detect the expression of ionized calcium-binding adaptor molecule 1 （IBA1）， CD16/32， and CD206. Real-time PCR was performed to measure the mRNA levels of CD206， CD163， inducible nitric oxide synthase （iNOS）， and arginase 1 （Arg-1）. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of nerve growth factor （NGF）， iNOS， and Arg-1. The nitric oxide （NO） concentration was determined via the nitrate reductase method. ResultsCompared with the blank control group， the model group showed increased expression of IBA1 and CD16/32 （P<0.01）， decreased expression of CD206 （P<0.05）， upregulation in the mRNA level （P<0.01） and content （P<0.05） of iNOS， downregulation in the mRNA levels of CD206， CD163， and Arg-1 （P<0.05， P<0.01）， lowered levels of Arg-1 and NGF （P<0.05）， and an elevation in the NO level （P<0.05）. Compared with the model group， the XXT-medicated serum group exhibited reduced expression of IBA1 and CD16/32 （P<0.05， P<0.01） and increased expression of CD206 （P<0.01）. Both the content and mRNA level of iNOS were downregulated （P<0.05， P<0.01）， while the mRNA levels of CD206， CD163， and Arg-1 were upregulated （P<0.01） in the XXT-medicated serum group. In addition， the XXT-medicated serum group showed elevated levels of Arg-1 and NGF （P<0.05） and a lowered level of NO （P<0.05）. The blank serum group showed no statistically significant differences in the measured parameters compared with the model group. ConclusionThe XXT-medicated serum can inhibit the polarization toward the M1 phenotype and promote the polarization toward the M2 phenotype， exerting anti-inflammatory and neurotrophic effects.