Resveratrol alleviates MSU-induced gouty arthritis in rats through inhibition of HIF-1α- and NLRP3-derived IL-1ß secretion in macrophages.

Gouty arthritis is an acute and chronic joint inflammatory joint disease characterized by the deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. Resveratrol (3, 5, 4-trihydroxy-trans-stilbene, RV), a natural polyphenolic compound, has anti-inflammatory and antioxidant properties. The purpose of this study was to investigate the effect of resveratrol on rats with gouty arthritis and its molecular mechanism. THP-1-derived macrophages were induced by lipopolysaccharide (LPS) and MSU to create an in vitro gout cell inflammation model, and rats were injected with MSU crystals into the right ankle joint for an in vivo acute gouty arthritis model. We investigated the anti-inflammatory properties of resveratrol using these in vitro and in vitro models. Our findings suggested that resveratrol effectively reduced ankle swelling and synovial inflammation in a dose-dependent manner in rats with acute gouty arthritis, with almost the same effect as colchicine treatment. In MSU-treated THP-1-derived macrophages, resveratrol inhibited NLRP3 inflammasome activation and IL-1ß secretion. Furthermore, resveratrol and the HIF-1α inhibitor PX478 both inhibited the expression of the NLRP3 inflammasome, IL-1ß, and HIF-1α. This study demonstrated that resveratrol significantly improved the symptoms of acute gouty arthritis and its potential mechanism may be IL-1ß reduction via HIF-1α modulation and inhibition of NLRP3 inflammasome activation. Our study might offer a novel sight for the treatment of gouty arthritis.

A metabonomic study to explore potential markers of asymptomatic hyperuricemia and acute gouty arthritis.

BACKGROUND: Acute gouty arthritis (AGA) is a metabolic disease with acute arthritis as its main manifestation. However, the pathogenesis of asymptomatic hyperuricemia (HUA) to AGA is still unclear, and metabolic markers are needed to early predict and diagnose. In this study, gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) was used to reveal the changes of serum metabolites from healthy people to HUA and then to AGA, and to find the pathophysiological mechanism and biological markers. METHODS: Fifty samples were included in AGA, HUA, and healthy control group, respectively. The metabolites in serum samples were detected by GC/LC-MS. According to the statistics of pairwise grouping, the statistically significant differential metabolites were obtained by the combination of multidimensional analysis and one-dimensional analysis. Search the selected metabolites in KEGG database, determine the involved metabolic pathways, and draw the metabolic pathway map in combination with relevant literature. RESULTS: Using metabonomics technology, 23 different serum metabolic markers related to AGA and HUA were found, mainly related to uric acid metabolism and inflammatory response caused by HUA/AGA. Three of them are completely different from the previous gout studies, nine metabolites with different trends from conventional inflammation. CONCLUSIONS: In conclusion, we analyzed 150 serum samples from AGA, HUA, and healthy control group by GC/LC-MS to explore the changes of these differential metabolites and metabolic pathways, suggesting that the disease progression may involve the changes of biomarkers, which may provide a basis for disease risk prediction and early diagnosis.

[The expression of semaphorins in synovial tissue of knee joint in patients with rheumatoid arthritis is increased and positively correlated with clinical inflammatory markers].

Objective To investigate the expression level of semaphorin 3C (SEMA3C) and semaphorin 3F (SEMA3F) in synovial tissue of patients with rheumatoid arthritis (RA), and to analyze its correlation with clinical inflammatory markers and its clinical application value. Methods Knee joint synovial tissue specimens of 8 patients with RA and 8 patients with osteoarthritis (OA) were studied. The expression and distribution of SEMA3C, SEMA3F and tyrosine hydrogenase (TH) in synovial tissues were detected by immunohistochemistry. The mRNA and protein expression levels of SEMA3C and SEMA3F in synovial tissue were detected by real-time quantitative PCR and Western blot respectively. The correlations of SEMA3C and SEMA3F expression levels with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (ACPA), platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) were analyzed by Pearson method. Results Compared with those in synovial tissue of patients with OA, the distribution of SEMA3C and SEMA3F in synovial tissue of patients with RA was more extensive, while the expression of TH decreased. SEMA3C and SEMA3F mRNA and protein expressions in synovial tissue of patients with RA increased. Protein expression level of SEMA3C was negatively correlated with MPV and positively correlated with RF; protein expression level of SEMA3F was positively correlated with ESR and negatively correlated with PDW. Conclusion SEMA3C and SEMA3F are highly expressed in synovial tissue of patients with RA and correlated with the clinical inflammatory markers, which is expected to provide reference for the clinical evaluation of disease progression.