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Objective To observe the effect of sirtuin 1(SIRT1)on rat myocardial fibrosis induced by pressure overload and the proliferation of cardiac fibroblasts induced by angiotensin Ⅱ(Ang Ⅱ),and to explore the molecular mechanisms.Methods The pressure overload-induced myocardial fibrosis was established by abdominal aorta constriction(AAC)procedure in vi-vo.After treatment with SIRT1 activator,the myocardial interstitial fibrosis and the collagen volume fraction were evaluated by Masson's trichrome staining.The protein expressions of TGF-β1/Smads were determined by immunohistochemical analy-sis.After in vitro intervention of Ang Ⅱ or Ang Ⅱ with SIRT1 activator,the fibroblasts proliferation was detected by MTT as-say.The mRNA and protein expressions of collagen Ⅰ/Ⅲ(Col1α1/3α1),SIRT1 and TGF-β1/Smads in myocardial tissue and fi-broblasts were evaluated by qRT-PCR and Western blotting.Results Compared with the sham operation group,myocardial in-terstitial fibrosis was significantly observed in the pressure overload model group,myocardial collagen volume fraction was in-creased,expressions of Col1α1/3α1 and TGF-β1/Smads were significantly increased,and SIRT1 expression was decreased.After the intervention of SRT1720,SIRT1 activator could improve the myocardial interstitial fibrosis induced by pressure overload,downregulate the expressions of Col1α1/3α1 and TGF-β1/Smads,and upregulate the expression of SIRT1.Meanwhile,correla-tion analysis showed that the protein expression of SIRT1 was negatively correlated with the expression of TGF-β1.In addition,SRT1720 also inhibited Ang Ⅱ-induced fibroblast proliferation and increased expression of Col1α1/3α1 and TGF-β1.Conclusion Activation of SIRT1 inhibits pressure overload-induced myocardial fibrosis and Ang Ⅱ-induced fibroblasts proliferation via regu-lation of the TGF-β1/Smads signaling pathway.
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Objective:To explore the effect of Chaihu Longgu Mulitang on intestinal microflora diversity of schizophrenic model rats, and further reveal its therapeutic characteristics and mechanisms based on the 16S rRNA technique. Method:Except the normal group, male SD rats were intraperitoneally injected dizocilpine maleate with daily dose of 0.1 mg·kg-1.After the success of the model, Chaihu Longgu Mulitang high, middle and low dose groups were converted into the human clinical upper limit daily, and the experimental rats were given Chaihu Longgu Mulitang with doses of 11.2, 5.6, 2.8 g·kg-1, respectively. And the positive drug group was treated with 0.4 mg·kg-1 of risperidone tablets.The normal group and model group was treated with water.The rats were continuous administrated 14 days with dosing volume of 10 mL·kg-1, the contents in caecum of rats were taken after anesthesia.Illumina MiSeq was used as the sequencing platform, the number of operational taxonomic units(OTUs), richness and diversity indexes, diversity of alpha and beta, differential phylum and genus of intestinal flora in V4 zone of 16S rRNA were comprehensively analyzed and evaluated. Result:Chaihu Longgu Mulitang could improve the number of OTUs, richness and diversity indexes of intestinal flora, imbalance of alpha and beta diversity of schizophrenic model rats.And this formula had a callback effect on 5 differential phyla of bacteria(Bacteroidetes, Acidobacteria, Proteobacteria, Firmicutes and TM7) and 20 genera of bacteria in schizophrenic model rats. Conclusion:Chaihu Longgu Mulitang plays an therapeutic effect on diversity of abnormal microflora in schizophrenic model rats, and this paper reveals the pathological mechanism of intestinal microflora in the state of schizophrenia by 16S rRNA technique.
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The Chinese herbal Radix Scrophulariae is the main medicine for nourishing yin and reducing fire. It can be used to treat hyperthyroidism due to yin deficiency and fire hyperactivity, but its mechanism is not clear. The present study was aimed to explore the mechanism of Radix Scrophulariae treatment of hyperthyroidism due to yin deficiency and fire hyperactivity. The urine metabolomic approach was conducted using the method of UPLC-TOF-MS. The results showed that Radix Scrophulariae has good therapeutic effects on hyperthyroidism rat model of yin deficiency. After treatment with Radix Scrophulariae, through metabolic profiling and protocol analysis, 6 potential metabolic markers may be closely related with the treatment mechanism of Radix Scrophulariae on this disease, including proline betaine, estrone, thymidine, 5-hydroxyindoleacetic acid, cyclic AMP and L-dopa. The strongest metabolic pathways were associated with tryptophan metabolism, pyrimidine metabolism, tyrosine metabolism, purine metabolism and steroid hormone biosynthesis. The urine metabolomic approach can be applied to clarify the therapeutic mechanism of Radix Scrophulariae on hyperthyroidism rat of yin deficiency, and provide the theoretical basis for the clinical practice of Radix Scrophulariae on nourishing yin to reduce pathogenic fire.