دورية أكاديمية
Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy.
| العنوان: | Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy. |
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| المؤلفون: | Guo X; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Xue M; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Li CJ; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Yang W; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Wang SS; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Ma ZJ; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Zhang XN; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Wang XY; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Zhao R; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Chang BC; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China., Chen LM; Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China. Electronic address: xfx22081@vip.163.com. |
| المصدر: | Journal of ethnopharmacology [J Ethnopharmacol] 2016 Dec 04; Vol. 193, pp. 333-344. Date of Electronic Publication: 2016 Aug 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Sequoia Original Publication: Lausanne, Elsevier Sequoia. |
| مواضيع طبية MeSH: | Autoimmune Diseases/*prevention & control , Cardiomyopathies/*prevention & control , Diabetic Cardiomyopathies/*complications , Diterpenes/*pharmacology , Inflammation/*prevention & control , Phenanthrenes/*pharmacology , Toll-Like Receptor 4/*physiology, Animals ; Autoimmune Diseases/complications ; Blood Glucose/metabolism ; Cardiomyopathies/complications ; Epoxy Compounds/pharmacology ; Fibrosis ; Heart Function Tests/drug effects ; Immunity, Innate/drug effects ; Inflammation/complications ; Male ; Rats ; Rats, Sprague-Dawley |
| مستخلص: | Ethnopharmacological Relevance: Triptolide is a most important active ingredient extracted from traditional Chinese medicine Tripterygium, which has been widely used to treat glomerulonephritis as well as immune-mediated disorders, likely for its immunosuppressive, anti-proliferative and anti-inflammatory effects. Aim of the Study: In this study, we have investigated the potential protective effects of triptolide against diabetic cardiomyopathy (DCM) by regulating immune system, attenuating inflammatory response, thus resulting in decreased cardiac fibrosis and improved left ventricle function. Materials and Methods: Sprague-Dawley rats were randomly divided into 5 groups: normal group, diabetic group and diabetic rats treated with triptolide (50, 100, or 200μg/kg/day resp) for 8 weeks. Cardiac function was performed by echocardiography and histopathology of the hearts was examined with HE, Masson staining and scanning electron microscopy. Immune regulation mediator, macrophage infiltration, inflammatory response and cardiac fibrosis related cytokines were measured by RT-PCR, Western blot and Immunohistochemistry staining. Results: In the diabetic group, the expressions of TLR4 and NF-κB p65 were both up-regulated, which was associated with increased pro-inflammatory cytokines, coupled with cardiac fibrosis and impaired left ventricular function. Interestingly, pathological structure and function of left ventricle were both significantly improved in the triptolide treated groups. Furthermore, the immune mediator TLR4, downstream activator NF-κB p65, macrophage infiltration (CD68+), pro-inflammatory cytokines (TNF-α, IL-1β), cell adhesion molecule (VCAM-1) and chemokine (MCP-1) were significantly suppressed when treated with medium and high dosage triptolide compared with the diabetic group. Moreover, cardiac fibrosis pathway including α-SMA, TGF-β1, vimentin and collagen accumulations were observed significantly decreased in the triptolide treated groups. Conclusions: Our data demonstrated that the protective effects of triptolide against DCM might attribute to inhibition of TLR4-induced NF-κB/IL-1β immune pathway, suppression of NF-κB/TNF-α/VCAM-1 inflammatory pathway and down-regulation of TGF-β1/α-SMA/Vimentin fibrosis pathway. (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Diabetic cardiomyopathy; Fibrosis; Immune; Inflammation; Triptolide; Triptolide (PubChem CID: 107985) |
| المشرفين على المادة: | 0 (Blood Glucose) 0 (Diterpenes) 0 (Epoxy Compounds) 0 (Phenanthrenes) 0 (Tlr4 protein, rat) 0 (Toll-Like Receptor 4) 19ALD1S53J (triptolide) |
| تواريخ الأحداث: | Date Created: 20160826 Date Completed: 20170531 Latest Revision: 20170531 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.jep.2016.08.029 |
| PMID: | 27558948 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7573 |
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| DOI: | 10.1016/j.jep.2016.08.029 |