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BACKGROUND:Knee osteoarthritis is a common clinical degenerative joint disease characterized by chronic inflammation and oxidative stress.Resveratrol has anti-inflammatory and anti-oxidative stress biological effects,and therefore it can be used symptomatically and expected to provide a new strategy for the treatment of knee osteoarthritis. OBJECTIVE:To investigate the therapeutic effect and mechanism of resveratrol on knee osteoarthritis in rats through the silence information regulator 1(SIRT1)/forkhead transcription factor O1(FOXO1)pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into control group,model group,low-dose resveratrol group,and high-dose resveratrol group,with 10 rats in each group.Knee osteoarthritis models were established in the model group,low-dose resveratrol group,and high-dose resveratrol group.A mixture of 4%papain solution and 0.3 mol/L cysteine solution(1:1 for 0.5 hours;20 μL)was injected at 1,4,and 7 days after modeling.Rats in the low-dose and high-dose resveratrol groups were injected with 25 and 100 mg/kg resveratrol through the articular cavity at 1 day after successful modeling,while those in the control and model groups were injected with equivalent volume of physiological saline through the articular cavity.After 28 days of treatment,the maximum knee joint activity was measured;the levels of oxidative stress indicators and inflammatory factors in the synovial fluid of the knee joint were analyzed by radioimmunoassay and ELISA;the content of collagen fibers in the knee joint was analyzed by safranin O-fast green staining;the degree of arthritic lesions was analyzed using the Mankin histological score;and the levels of SIRT1 and FOXO1 in the knee joint were detected by western blot assay. RESULTS AND CONCLUSION:Compared with the model group,the maximum knee flexion and extension angles of rats significantly increased in the low-dose and high-dose resveratrol groups,and were significantly higher in the high-dose group than the low-dose group(P<0.05).Compared with the model group,the levels of superoxide dismutase and glutathione peroxidase in the knee joint fluid of rats significantly increased in the low-dose and high-dose resveratrol groups.The level of malondialdehyde significantly decreased in both resveratrol groups,and the level in the high-dose resveratrol group was significantly better than that in the low-dose resveratrol group(P<0.05).Compared with the model group,the low-dose and high-dose resveratrol groups showed a significant decrease in the levels of interleukin 1β,interleukin 6 and tumor necrosis factor α in the knee joint fluid of rats,and the levels of these inflammatory factors were significantly lower in the high-dose resveratrol group than the low-dose resveratrol group(P<0.05).Compared with the model group,the content of collagen fibers in the knee joint was significantly increased in both resveratrol groups,and the high-dose resveratrol group showed a higher content of collagen fibers than the low-dose resveratrol group(P<0.05).Compared with the model group,the expression level of SIRT1 in the knee joints of rats significantly increased in both resveratrol groups,while the level of acetylated FOXO1 significantly decreased(P<0.05).The magnitude of changes was significantly better in the high-dose group than the low-dose group.To conclude,resveratrol significantly improves the levels of oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis and alleviates arthritic symptoms in a dose-dependent manner,possibly through the SIRT1/FOXO1 pathway.
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Objective@# To investigate the effects of platelet-rich fibrin (PRF) and acellular dermal matrix (ADM) on the repair of oral mucosal defects and to provide the basis for soft tissue growth in oral implant operations.@*Methods@#Thirty-six healthy male Japanese big ear rabbits were randomly divided into the PRF group, ADM group, Autograft group (autologous connective tissue transplantation group) and Control group (blank control group); each group contained nine rabbits. Between the midline and the hard palate maxillary incisors, in an 8-mm location preparation and a 10-mm standard mucosa defect, the ADM group, PRF and Autograft group were implanted with ADM, autologous PRF and autologous cornification mucosa, respectively, whereas the control group had wound gauze compression processing at 7, 14, and 21 days to determine the wound healing rate in the area selected by HE staining. The inflammatory grade and average epithelial thickness were observed, and the results were statistically analyzed.@*Results @#Compared with the control group, the PRF, ADM and Autograft groups had significantly advanced wound healing (P < 0.05). The wound healing degree in the PRF group was similar to that of the ADM group at all time points (P > 0.05). The wound healing degree in the PRF and ADM groups was lower than that of the Autograft group at each time point (P < 0.05). HE staining results showed that compared with the control group, the levels of inflammation in the PRF group, ADM group and Autograft group were reduced, and the difference was statistically significant (P < 0.05). Nevertheless, there was no significant difference between the PRF, ADM and Autograft groups (P > 0.05). The epithelial thickness in the ADM group was similar to that in the Autograft group (P > 0.05). The epithelial thickness in the ADM group was higher than that in the PRF group at 7 d and 14 d (P < 0.05), but there was no significant difference at 21 d (P > 0.05).@*Conclusion @#PRF and ADM have similar healing effects in repairing oral mucosa defects, and they can be used as soft tissue augmentation materials instead of connective tissue transplantation.
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Objective To explore the synergism efficacy and mechanism of Warm Purgative and Strengthening Spleen (WPSS) therapy combined with antibiotics in the treatment of sepsis. Methods Thirty-two SPF Spargue-Dawley (SD) rats were used to replicate the rat sepsis model by cecum ligation perforation (CLP) method and equally divided into model control (MC) group, ceftriaxone group, Chinese herbal medicine (CHM) group and ceftriaxone +CHM group. Eight SD rats underwent sham surgery were used as a sham operation (Sham) group. Rats in Sham and MC groups were administered with 0.9% normal saline (NS) by intraperitoneal injection and gavage. Rats in CHM group were administered with modified Dahuang Fuzi Decoction (DFD, 8 mg/kg) by gavage + 0.9% NS by intraperitoneal injection, Bid. Rats in ceftriaxone group were administered with 0.9% NS by gavage and ceftriaxone (120 mg/kg) by intraperitoneal injection, Bid. Rats in ceftriaxone + CHM group were administered with modified DFD (8 mg/kg) by gavage and ceftriaxone (120 mg/kg) intraperitoneal injection, Bid. The drugs were given for 2 days. The mortality of rats in each group was observed after treatment. The intestinal flora changes and intestinal permeability [intestinal mucosa injury index (IMII), intestinal mucosa secretory immunoglobulin (sIgA), serum D-lactic acid, diamine oxidase (DAO) and sIgA] were detected. Meanwhile, the levels of serum inflammation indexes [lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were detected. Results ① Mortality: ceftriaxone+CHM group (25.0%) < CHM group (37.5%) and ceftriaxone group (37.5%) < MC group (50.0%), the differences between groups were statistically significant (all P < 0.05). ② 16S rDNA sequencing analysis: the ratio of Bacteroidetesin in MC group was lower than that in the Sham group [(24.36±7.15)% vs. (45.20±6.05)%], and the ratio of Proteobacteria in MC group was higher than that in Sham group [(10.03±7.55)% vs. (0.41±0.21)%]. The diversity of intestinal flora in ceftriaxone group was significantly lower than that in Sham and CHM groups (404.60±17.09 vs. 470.80±16.97, 469.20±14.59), the differences between groups were statistically significant (all P < 0.05). The principal component analysis (PCA) suggested that the composition of CHM group was closer to that of Sham group, which indicated that WPSS therapy could reduce intestinal flora disorders in rats with sepsis. ③The pathological changes of intestinal mucosa: light microscope showed the intestinal mucosa of Sham group was intact; the intestinal mucosa became thinner, and local inflammatory cells had infiltration in MC group. The thickness of intestinal mucosa in CHM, ceftriaxone and CHM+ceftriaxone groups was slightly thicker, and the infiltration of local inflammatory cells was less than that in MC group. The thickness of intestinal mucosa in CHM group and ceftriaxone+CHM group was slightly thicker than that in the ceftriaxone group, and the arrangement was more regular than that in MC group and ceftriaxone group.④Intestinal mucosa permeability and inflammatory state: IMII, D-lactic acid, DAO, LPS, TNF-α and IL-6 of rats in MC group were higher than those of rats in Sham group [IMII: 4.37±0.56 vs. 0.26±0.29, D-lactic acid (mg/L):12.35±0.83 vs. 7.30±1.29, DAO (kU/L): 2.16±0.43 vs. 0.32±0.06, LPS (kU/L): 0.663±0.012 vs. 0.095±0.003, TNF-α (μg/L): 251.03±82.69 vs. 52.15±6.25, IL-6 (μg/L): 160.50±4.77 vs. 54.30±3.36], while sIgA in MC group was lower than that in Sham group (mg/L: 11.57±0.17 vs. 26.76±1.99). IMII, D-lactic acid, DAO, LPS, TNF-α and IL-6 of rats in CHM, ceftriaxone and CHM+ ceftriaxone groups were significantly lower than those of rats in MC group, while sIgA in CHM, ceftriaxone and CHM+ceftriaxone groups were significantly higher than that of rats in MC group. The change of CHM+ceftriaxone group was more significant than those of CHM group and ceftriaxone group [IMII:1.78±0.23 vs. 1.96±0.62, 3.39±0.43, D-lactic acid (mg/L): 8.56±0.37 vs. 9.62±0.57,11.42±0.39, DAO (kU/L):1.14±0.12 vs. 1.72±0.24, 2.01±0.32, sIgA (mg/L): 25.34±1.49 vs. 23.99±7.85, 17.46±1.20, LPS (kU/L):0.302±0.007 vs. 0.387±0.004, 0.715±0.013, TNF-α (μg/L): 57.10±3.98 vs. 101.49±21.49, 141.91±20.20, IL-6 (μg/L): 93.71±2.39 vs. 87.12±7.31, 104.27±1.84]. Conclusion WPSS therapy may improve the efficacy of antibiotics in the treatment of sepsis by regulating the intestinal flora and reducing the intestinal mucosa permeability and inflammation level.
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Objective To study the effects of hypothermia therapy on inflammation level and safety of patients with severe nervous injury.Methods A total of 82 patients with severe nerve injury were divided into study group and control group by random digits table, 41 patients in each group.The patients in these two groups had no statistical dis-parities in inflammatory agent and intracranial pressure (p>0.05).The patients in the control group were treated by routine therapy and those in the study group were treated by cephalic hypothermia therapy additionally.The two groups were compared in terms of the level of TNFα, IL-6 and IL-8 in the cerebrospinal fluid, prognosis and safety.Re-sults Before treatment there was no significant difference in inflammation level between the two groups (p>0.05). After treatment, the TNFα, IL-6 and IL-8 levels in the study group were significantly lower than those in control group (p0.05).How-ever, after treatment there was a significant difference in ICP between the two groups in all time points (p0.0).Conclusion The hypothermia therapy has a great clini-cal efficacy and safety on severe never injury patients, which makes it worth clinical application.