A Novel Rat Model of Persistent Gouty Arthritis by Minimally Invasive Saturated Msu Embedding

Abstract Background: Animal models are valid for in vivo research on the pathophysiological process and drug screening of gout arthritis. Intra-articular injection of monosodium urate (MSU) is commonly used to establish animal model at present, while stable MSU deposition and tophi formation were rarely reported. Method: A total of twenty-four rats were randomly allocated into six groups. Three intervention groups of rats received MSU embedment for 3-5 times, respectively. Sham groups received pseudo surgeries with normal saline (NS). Gross parameters and pathological features of synovium harvested from anterior capsule. Mechanical pain threshold tests of rats were conducted over a 96-hour period postoperatively. Result: Significant synovial swelling was detected in the MSU group compared to the sham group(P<0.05). Behavioral tests showed that the embedding of MSU resulted in prolonged mechanical hyperalgesia (P<0.05 during 2 hours to 96 hours postoperatively). MSU depositions enveloped by neutrophil extracellular traps (NETs) were detected where the IL-1β and TNF-α were co-expressed in embedding groups. Quantitative immunofluorescence suggested that the frequencies of MSU interventions promoted expression of proinflammatory factors (P<0.05).Conclusion: A minimally invasive surgical method was developed to establish the novel rat model of intra-articular MSU deposition. This model was proved to be a simple reproducible method to mimic the pathological characteristics of intra-articular crystal arthritis.

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Minimally Invasive Embedding of Saturated MSU Induces Persistent Gouty Arthritis in Modified Rat Model

BioMed Research International ◽

10.1155/2021/6641701 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Han-Lin Xu ◽

Sheng-Kun Li ◽

Xiao-Ao Xue ◽

Zi-Yi Chen ◽

Ying-Hui Hua

Keyword(s):

Minimally Invasive ◽

Rat Model ◽

Gouty Arthritis ◽

Inflammatory Cells ◽

Tnf Α ◽

Quantitative Immunofluorescence ◽

Invasive Method ◽

Reproducible Method ◽

Mechanical Pain Threshold

Introduction. Animal models are valid for in vivo research on the pathophysiological process and drug screening of gout arthritis. Intra-articular injection of monosodium urate (MSU) is the most common method, while stable MSU deposition enveloped by inflammatory cells was rarely reported. Objective. To develop a modified gouty arthritis rat model characterized by intra-articular MSU deposition and continuous joint pain with a minimally invasive method. Method. A total of twenty-four rats were randomly allocated into six groups. Three intervention groups of rats received intra-articular MSU embedment. Sham groups received pseudosurgeries with equal normal saline (NS). Gross parameters and pathological features of synovium harvested from anterior capsule were estimated. Mechanical pain threshold tests were conducted over a 96-hour period postoperatively. Moreover, quantitative immunofluorescence was conducted to assess tissue inflammation. Result. After MSU embedding, rats got more persistent arthritic symptoms as well as tissue MSU deposition. More significant synovial swelling was detected in the MSU group compared to sham groups ( P < 0.025 ). Behavioral tests showed that the embedding of MSU resulted in prolonged mechanical hyperalgesia during 2 hours to 96 hours postoperatively ( P < 0.05 ). MSU depositions enveloped by inflammatory cells that express IL-1β and TNF-α were detected in embedding groups. Quantitative immunofluorescence suggested that the frequencies of MSU interventions upregulated expression of proinflammatory factors including IL-1β and TNF-α ( P < 0.05 ). Conclusion. A minimally invasive method was developed to establish modified rat model of intra-articular MSU deposition. This model was proved to be a simple reproducible method to mimic the pathological characteristics of persistent gouty arthritis.

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Nonstressed rat model of acute endotoxemia that unmasks the endotoxin-induced TNF-α response

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.2.h671 ◽

1999 ◽

Vol 276 (2) ◽

pp. H671-H678 ◽

Cited By ~ 3

Author(s):

David W. A. Beno ◽

Robert E. Kimura

Keyword(s):

Rat Model ◽

Endotoxic Shock ◽

Stress Hormones ◽

Tnf Α ◽

Baseline Concentrations ◽

Experimental Protocols ◽

Factor Α ◽

Necrosis Factor

Previous investigators have demonstrated that the tumor necrosis factor-α (TNF-α) response to endotoxin is inhibited by exogenous corticosterone or catecholamines both in vitro and in vivo, whereas others have reported that surgical and nonsurgical stress increase the endogenous concentrations of these stress-induced hormones. We hypothesized that elevated endogenous stress hormones resultant from experimental protocols attenuated the endotoxin-induced TNF-α response. We used a chronically catheterized rat model to demonstrate that the endotoxin-induced TNF-α response is 10- to 50-fold greater in nonstressed (NS) rats compared with either surgical-stressed (SS, laparotomy) or nonsurgical-stressed (NSS, tail vein injection) models. Compared with the NS group, the SS and NSS groups demonstrated significantly lower mean peak TNF-α responses at 2 mg/kg and 6 μg/kg endotoxin [NS 111.8 ± 6.5 ng/ml and 64.3 ± 5.9 ng/ml, respectively, vs. SS 3.9 ± 1.1 ng/ml ( P < 0.01) and 1.3 ± 0.5 ng/ml ( P < 0.01) or NSS 5.2 ± 3.2 ng/ml ( P < 0.01) at 6 μg/kg]. Similarly, baseline concentrations of corticosterone and catecholamines were significantly lower in the NSS group [84.5 ± 16.5 ng/ml and 199.8 ± 26.2 pg/ml, respectively, vs. SS group 257.2 ± 35.7 ng/ml ( P< 0.01) and 467.5 ± 52.2 pg/ml ( P < 0.01) or NS group 168.6 ± 14.4 ng/ml ( P < 0.01) and 1,109.9 ± 140.7 pg/ml ( P < 0.01)]. These findings suggest that the surgical and nonsurgical stress inherent in experimental protocols increases baseline stress hormones, masking the endotoxin-induced TNF-α response. Subsequent studies of endotoxic shock should control for the effects of protocol-induced stress and should measure and report baseline concentrations of corticosterone and catecholamines.

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The Anti-Inflammatory Effects of Angiogenin in an Endotoxin Induced Uveitis in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms21020413 ◽

2020 ◽

Vol 21 (2) ◽

pp. 413

Author(s):

Jihae Park ◽

Jee Taek Kim ◽

Soo Jin Lee ◽

Jae Chan Kim

Keyword(s):

Western Blot ◽

Inflammatory Cytokines ◽

Aqueous Humor ◽

Rat Model ◽

Inflammatory Responses ◽

Inflammatory Cells ◽

Ocular Tissue ◽

Tnf Α ◽

Anti Inflammatory

Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1β, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.

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In vivo efficacy of the novel hemostatic agent Poly DHA in an experimental rat model

Journal of Plastic Reconstructive & Aesthetic Surgery ◽

10.1016/j.bjps.2009.02.013 ◽

2009 ◽

Vol 62 (6) ◽

pp. 833S-834S

Author(s):

D.J. Kadouch ◽

P. Henderson ◽

S.P. Singh ◽

P.N. Zawaneh ◽

D. Putnam ◽

...

Keyword(s):

Rat Model ◽

Hemostatic Agent ◽

The Novel ◽

In Vivo Efficacy ◽

Experimental Rat Model

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Full Dimensional Intuitive Motion Mapping Strategy for Minimally Invasive Surgical Robot with Redundant Passive Joints

Journal of Medical Devices ◽

10.1115/1.4049312 ◽

2020 ◽

Author(s):

Kang Kong ◽

Shuxin Wang ◽

Jianmin Li ◽

He Su

Keyword(s):

Minimally Invasive ◽

Mapping Method ◽

Control Technique ◽

Direct Control ◽

Minimally Invasive Surgical ◽

Mapping Strategy ◽

Orientation Mapping ◽

Position And Orientation ◽

Limited Motion

Abstract Adding redundant passive joints to a robotic arm is an effective way to make the robot overcome the inherent incision constraint of minimally invasive surgery (MIS). However, due to the limited motion accuracy, it is difficult to realize full-dimensional intuitive motion based on traditional multi-axis coordinated control technology in this kind of MIS robots. To solve this problem, a separated position and orientation mapping strategy for MIS robot with redundant passive joints is proposed in the paper. The position and orientation mapping of the strategy are realized by coordinate motion control and joint direct control technique, respectively. To realize the intuitive motion under this condition, an inverse motion mapping method is further proposed. Compared with the existing mapping strategy, the proposed strategy is much more compact as the orientation mapping is greatly simplified. A large number of in-vivo trials based on the newly developed prototype have been conducted and results fully verify the effectiveness of the proposed strategy.

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Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes

Journal of Endocrinology ◽

10.1677/joe.1.06211 ◽

2005 ◽

Vol 185 (3) ◽

pp. R1-R8 ◽

Cited By ~ 111

Author(s):

Susan Kralisch ◽

Johannes Klein ◽

Ulrike Lossner ◽

Matthias Bluher ◽

Ralf Paschke ◽

...

Keyword(s):

Insulin Resistance ◽

Hormonal Regulation ◽

The Novel ◽

Insulin Mimetic ◽

The Metabolic Syndrome ◽

Tnf Α ◽

Core Components ◽

Dose Dependent

Recently, visfatin was characterized as a novel adipo-cytokine that is upregulated in obesity and exerts insulin-mimetic effects in various tissues. To clarify expression and regulation of this adipocytokine, visfatin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction in 3T3-L1 adipocytes during adipogenesis and after treatment with various hormones known to alter insulin sensitivity. Visfatin expression was about 6-fold higher in 3T3-L1 adipocytes in vitro as compared with epididymal fat in vivo and increased during adipogenic conversion more than 3-fold. Interestingly, 100 nM dexamethasone significantly increased visfatin mRNA by almost 1.5-fold. In contrast, 500 ng/ml growth hormone (GH), 10 ng/ml tumor necrosis factor (TNF) α, and 10 μM isoproterenol downregulated visfatin expression by 45%, 36%, and 43% respectively. Insulin did not influence synthesis of this adipocytokine. The effects of dexamethasone, GH, TNFα and isoproterenol were time- and dose-dependent. Furthermore, activation of Gs-protein-coupled pathways by forskolin and cholera toxin was sufficient to significantly downregulate visfatin mRNA. Taken together, our results show a differential regulation of visfatin mRNA by insulin resistance-inducing hormones, supporting the view that this adipo-cytokine might be an interesting novel candidate linking core components of the metabolic syndrome such as obesity and insulin resistance.

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Anti-Gout Effects of the Medicinal Fungus Phellinus igniarius in Hyperuricaemia and Acute Gouty Arthritis Rat Models

Frontiers in Pharmacology ◽

10.3389/fphar.2021.801910 ◽

2022 ◽

Vol 12 ◽

Author(s):

Hongxing Li ◽

Xinyue Zhang ◽

Lili Gu ◽

Qín Li ◽

Yue Ju ◽

...

Keyword(s):

Rat Model ◽

Biological Activities ◽

Chemical Constituents ◽

Gouty Arthritis ◽

Therapeutic Effects ◽

Acute Gouty Arthritis ◽

Rat Models ◽

Phellinus Igniarius ◽

Anti Inflammatory

Background:Phellinus igniarius (P. igniarius) is an important medicinal and edible fungus in China and other Southeast Asian countries and has diverse biological activities. This study was performed to comparatively investigate the therapeutic effects of wild and cultivated P. igniarius on hyperuricaemia and gouty arthritis in rat models.Methods: UPLC-ESI-qTOF-MS was used to identify the chemical constituents of polyphenols from wild P. igniarius (WPP) and cultivated P. igniarius (CPP). Furthermore, WPP and CPP were evaluated in an improved hyperuricaemia rat model induced by yeast extract, adenine and potassium oxonate, which was used to examine xanthine oxidase (XO) activity inhibition and anti-hyperuricemia activity. WPP and CPP therapies for acute gouty arthritis were also investigated in a monosodium urate (MSU)-induced ankle swelling model. UHPLC-QE-MS was used to explore the underlying metabolic mechanisms of P. igniarius in the treatment of gout.Results: The main active components of WPP and CPP included protocatechuic aldehyde, hispidin, davallialactone, phelligridimer A, hypholomine B and inoscavin A as identified by UPLC-ESI-qTOF-MS. Wild P. igniarius and cultivated P. igniarius showed similar activities in reducing uric acid levels through inhibiting XO activity and down-regulating the levels of UA, Cr and UN, and they had anti-inflammatory activities through down-regulating the secretions of ICAM-1, IL-1β and IL-6 in the hyperuricaemia rat model. The pathological progression of kidney damage was also reversed. The polyphenols from wild and cultivated P. igniarius also showed significant anti-inflammatory activity by suppressing the expression of ICAM-1, IL-1β and IL-6 and by reducing the ankle joint swelling degree in an MSU-induced acute gouty arthritis rat model. The results of metabolic pathway enrichment indicated that the anti-hyperuricemia effect of WPP was mainly related to the metabolic pathways of valine, leucine and isoleucine biosynthesis and histidine metabolism. Additionally, the anti-hyperuricemia effect of CPP was mainly related to nicotinate and nicotinamide metabolism and beta-alanine metabolism.Conclusions: Wild P. igniarius and cultivated P. igniarius both significantly affected the treatment of hyperuricaemia and acute gouty arthritis models in vivo and therefore may be used as potential active agents for the treatment of hyperuricaemia and acute gouty arthritis.

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Phillygenin Alleviates Lipopolysaccharide-Induced Acute Pneumonia by Modulating the Tumor Necrosis Factor α Signaling Pathway

10.21203/rs.3.rs-450401/v1 ◽

2021 ◽

Author(s):

Cong-jie Wang ◽

Yu-jun Tan ◽

Chang-jun Lv ◽

Zhong Liu ◽

Gui-min Zhang ◽

...

Keyword(s):

Rat Model ◽

A549 Cells ◽

Pregnane X Receptor ◽

Bioinformatic Analysis ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Reporter Assay ◽

Tnf Α ◽

Acute Pneumonia

Abstract Purpose: There is an urgent need to develop effective anti-pneumonia drugs. Phillygenin (PHI) is derived from Forsythia suspense and possesses anti-inflammation, anti-oxidant bioactivities. In the present study, we aimed to evaluate the therapeutic potential of phillygenin (PHI) on lipopolysaccharide (LPS)-induced acute pneumonia.Methods: The molecular target of PHI was predicted by bioinformatic analysis. Hollow fiber-based ligand fishing (HFLF) strategy and luciferase reporter assay were further used to identify the target of PHI. LPS-induced acute pneumonia rat model and A549 cells model were used to evaluate PHI function. TNF-α pathway and apoptosis associated proteins were detected by Western Blot, immunofluorescence and immunohistochemistry. Cell cycle and cytokines were determined by flow cytometry.Results: The bioinformatic analysis and luciferase reporter assay identified that the target protein of PHI was pregnane X receptor (PXR) PHI could directly bind to PXR protein and inhibit NF-κB P65 activity. PHI significantly decreased the expression of phosphorylated JNK, P38, Erk, P65 in acute pneumonia rat model. PHI also declined the expression of Bax, Caspase-3 and Caspase-9 and repressed lung epithelial cell apoptosis induced by LPS in vivo and in vitro. In addition, PHI inhibited inflammation cytokines production including TNF-α, IFN-γ, IL-6, IL-1β and IL-18.Conclusions: PHI significantly alleviated LPS-induced lung injury in vivo by exerting anti-inflammatory effects. This is the first study to demonstrate that PHI, a small molecule natural product, significantly alleviates LPS-induced acute pneumonia by binding to PXR. Thus, PHI can be a novel therapeutic agent for pneumonia.

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Benzylideneacetophenone Derivative Alleviates Arthritic Symptoms via Modulation of the MAPK Signaling Pathway

Molecules ◽

10.3390/molecules25153319 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3319

Author(s):

Bongjun Sur ◽

Mijin Kim ◽

Thea Villa ◽

Seikwan Oh

Keyword(s):

Rat Model ◽

Mapk Signaling ◽

Knee Joints ◽

Inhibitory Effects ◽

Arthritis Induction ◽

Tnf Α ◽

Necrosis Factor ◽

Fibroblast Like Synoviocytes

The benzylideneacetophenone derivative 3-(4-hydroxy-3-methoxy-phenyl)-1-{3-[1]-phenyl}-propenone (JC3 dimer) was synthesized through the dimerization of JC3. To investigate the inhibitory effects of JC3 dimer, the carrageenan/kaolin (C/K)-induced knee arthritis rat model was used in vivo and rheumatoid arthritis (RA) patient-derived fibroblast-like synoviocytes (FLS) were used in vitro. In the C/K rat model, JC3 dimer was given after arthritis induction for 6 days at the concentrations of 1, 5, or 10 mg/kg/day. Manifestation of arthritis was evaluated using knee thickness, weight distribution ratio (WDR), and squeaking test. The levels of prostaglandin E2 (PGE2), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in the serum of JC3 dimer-treated arthritic rats were also analyzed. Histological examination of the knee joints was also done. For the FLS, the cells were stimulated using IL-1β and concentrations of 1, 5, and 10 μg/mL JC3 dimer were used. The levels of IL-8, IL-6, and PGE2 were measured in stimulated FLS treated with JC3 dimer. At days 5 to 6 after arthritis induction, JC3 dimer treatment significantly decreased arthritic symptoms and reduced the inflammation in the knee joints in the histology of knee tissues in C/K-arthritic rats. In stimulated FLS, JC3 dimer suppressed the increase of IL-8, IL-6, and PGE2. These findings suggest that JC3 dimer has suppressive effects on arthritis, and that JC3 dimer can be a potential agent for arthritis therapy.

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