title: Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.
abstract: OBJECTIVE
  Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats.
  
  
  METHODS
  Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins.
  
  
  RESULTS
  DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine.
  
  
  CONCLUSIONS
  Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.
authors.affiliation: Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
authors.forename: Zhong-wei
authors.initials: ZW
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
authors.forename: Jun-kui
authors.initials: JK
authors.lastname: Wang
authors.affiliation: Department of Biostatistics & Bioinformatics, School of Public Health & Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
authors.forename: Gong-chang
authors.initials: GC
authors.lastname: Guan
authors.affiliation: Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
authors.forename: Xin-hong
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
authors.forename: Shang-jian
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
authors.forename: Zheng-rong
authors.initials: ZR
authors.lastname: Deng
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011807:Quinolizines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left / Q000187:drug effects*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D002316:Cardiotonic Agents; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D011807:Quinolizines; D017382:Reactive Oxygen Species; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D000093842:Matrines