ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Simiao Wan (SMW) is a classical traditional Chinese medicine (TCM) prescription to empirically treat gouty arthritis (GA) in TCM clinical practice. However, the potential mechanisms of SMW on GA are not fully evaluated. AIM OF STUDY: The aim of this study is to investigate the role of macrophage polarization in the anti-GA activity of SMW. MATERIALS AND METHODS: Rats were intragastricly treated with SMW for consecutive 7 days. On day 6, monosodium urate (MSU) crystal-induced arthritis (MIA) in the ankle joint was prepared. Paw volume, gait score and histological score were measured. Levels of interleukin (IL)-1ß and IL-10 in serum were detected by enzyme-linked immunosorbent assay. Expressions of inducible nitric oxide synthase (iNOS), arginase (Arg)-1, phosphorylated (p)-p65, inhibitor of nuclear factor (NF)-κB (IκB)α, p-signal transducer and transcription activator (STAT)3 and p-Janus kinase (JAK)2 in synovial tissues were determined by Western blot. RESULTS: The elevated paw volume, gait score and histological score in MIA rats were significantly decreased by SMW treatment. Meanwhile, SMW significantly decreased the IL-1ß level and increased the IL-10 level in serum of MIA rats. Furthermore, SMW reduced the expressions of iNOS, p-p65 and enhanced the expressions of Arg-1, IκBα, p-STAT3 and p-JAK2 in synovial tissues of MIA rats. CONCLUSIONS: The results suggest that SMW attenuates the inflammation in MIA rats through promoting macrophage M2 polarization.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Arthritis, Experimental/prevention & control , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Macrophages/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Antirheumatic Agents/chemistry , Arginase/metabolism , Arthritis, Experimental/pathology , Drugs, Chinese Herbal/chemistry , Edema/chemically induced , Edema/drug therapy , Edema/pathology , Extremities/pathology , Gait/drug effects , I-kappa B Proteins/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/pathology , Interleukin-10/metabolism , Interleukin-1beta/metabolism , Janus Kinase 2/metabolism , Macrophage Activation/drug effects , Macrophages/metabolism , Male , Neoplasm Proteins/metabolism , Nitric Oxide Synthase Type II/metabolism , Nucleocytoplasmic Transport Proteins/metabolism , Rats, Sprague-Dawley , STAT3 Transcription Factor/metabolism , Synovial Membrane/drug effects , Synovial Membrane/metabolism , Uric Acid/toxicityABSTRACT
Biomechanical methods may provide a novel way to understand blood accumulation in intracerebral hemorrhage (ICH). The current study presents the results of a biomechanical analysis of blood accumulation in ICH using a finite element analysis, with an emphasis on the pressure exerted by the mass effect of blood in early ICH. A two-dimensional finite model of the human brain parenchyma and the human ventricular system was developed and analyzed under two preloading conditions. The material properties of the human parenchyma were derived from previous reports. Ogden's theory was applied to describe the stress-strain association in soft tissue. The results of the present study indicated that maximal stress was located at the two ends of the hemorrhage cavity, with the majority of stresses distributed on the zone surrounding the bleed. The two load environments demonstrated similar stress distributions. The loads put on the detached edges were not less than the intracranial pressure (ICP) when the stress threshold was reached. The results of the present study suggest that the direction of blood accumulation can be determined by the shape of the initial blood mass. Mechanical factors (blood pressure and ICP) did not serve a definitive role in preventing blood from accumulating in the early stages of ICH. The present study may aid in understanding the effects of mechanical factors in blood accumulation and hemostasis in patients with early ICH.
ABSTRACT
Intracerebral hemorrhage (ICH) may lead to physical and pathological damage and has been a focus of research for decades. Evaluating tensile damage caused by deformation in ICH is an important component of damage assessment for correct diagnosis and treatment. Traditional research on ICH paid little attention to quantified brain tissue damage resulting from mechanical factors, and only a few reported the mechanical properties of damaged brain tissue. The aim of the present study was to present an effective method that is able to evaluate the tissue damage degree in ICH, based on strain energy function. Two finite element analysis (FEA) models were analyzed: A three-dimensional (3D) model for tissue's tension experiment and a two-dimensional (2D) model for brain tissue's deformation in ICH. The polynomial fitting function of stress vs. stretch curve, which was derived from previous reports, was used in the FEA as the constitutive function of brain tissue. The present study demonstrated that white matter could be regarded as hyperelastic material when stretch was <1.343, and with stretch increasing, tissue injury exacerbated when stretch was >1.343. The strain energy loss was not linear in this process, and Neo-Hookean and Ogden model's results demonstrated a similar change in trend, but a difference in quantity. The results from 2D and 3D simulation, respectively, demonstrated the degree of damage according to the above dividing criteria and the possible distribution of tissue damage after ICH ictus. An analytical model from a biomechanical perspective for white matter injury in ICH may facilitate to improve clinical diagnosis and treatment.
