title: Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors: 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.
authors: Xin
authors: X
authors: Guo
authors: 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.
authors: Mei
authors: M
authors: Xue
authors: 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.
authors: Chun-Jun
authors: CJ
authors: Li
authors: 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.
authors: Wei
authors: W
authors: Yang
authors: 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.
authors: Shan-Shan
authors: SS
authors: Wang
authors: 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.
authors: Ze-Jun
authors: ZJ
authors: Ma
authors: 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.
authors: Xiao-Na
authors: XN
authors: Zhang
authors: 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.
authors: Xiao-Yu
authors: XY
authors: Wang
authors: 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.
authors: Ran
authors: R
authors: Zhao
authors: 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.
authors: Bao-Cheng
authors: BC
authors: Chang
authors: 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.
authors: Li-Ming
authors: LM
authors: Chen
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D009202:Cardiomyopathies / Q000150:complications / Q000517:prevention & control*; D058065:Diabetic Cardiomyopathies / Q000150:complications*; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005355:Fibrosis; D006334:Heart Function Tests / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000150:complications / Q000517:prevention & control*; D008297:Male; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C001899:triptolide
keywords: Diabetic cardiomyopathy; Fibrosis; Immune; Inflammation; Triptolide; Triptolide (PubChem CID: 107985)