Jian-Pi-Yin decoction attenuates lactose-induced chronic diarrhea in rats by regulating GLP-1 and reducing NHE3 ubiquitination and phosphorylation.

Objectives: Jian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. Design: In this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. Methods: The rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. Results: JPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. Conclusion: JPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. Innovation: In this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.

Dynamic Adjust of Non-Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR-II Imaging Mediated Photothermal Therapy and Immunotherapy.

Due to the aggregation-caused quenching effect and near-infrared I poor penetration capabilities of common fluorescent molecules, their applications in visualized imaging and photoactivated treatment are limited. Therefore, new near-infrared II (NIR-II) molecule (named TST), which had the abilities of aggregation-induced emission (AIE) and photothermal therapy are synthesized. Moreover, in order to further improve its fluorescent yield and therapeutic effect, camptothecin prodrug (CPT-S-PEG) and novel immune checkpoint inhibitor AZD4635 are used to co-assemble with TST into nanoparticles for drug delivery. On account of the strong interaction of camptothecin and TST, the intramolecular rotation of TST is limited, thereby inhibiting non-radiation attenuation and promoting fluorescence generation when the nanoparticles are intact. As nanoparticles uptake by cancer cells, redox sensitive CPT-S-PEG is degraded and the nanoparticles disintegrate. The released TST enhances non-radiative attenuation and expedites photothermal conversion because of the removal of the constraint of camptothecin. Furthermore, photothermal therapy induces immunogenic cell death of cancer cells and releases abundant ATP into the tumor microenvironment to recruit immune cells. However, superfluous ATP is converted into immunosuppressive adenosine through the CD39-CD73-A2AR pathway. The AZD4635 released by photothermal disintegration of the nanoparticles just blocks this pathway timely, achieving favorable synergistic effect of photothermal therapy, chemotherapy, and immunotherapy.

LianXia Formula Granule Attenuates Cardiac Sympathetic Remodeling in Rats with Myocardial Infarction via the NGF/TrKA/PI3K/AKT Signaling Pathway.

Sympathetic remodeling may cause severe arrhythmia after myocardial infarction (MI). Thus, targeting this process may be an effective strategy for clinical prevention of arrhythmias. LianXia Formula Granule (LXFG) can effectively improve the symptoms of patients with arrhythmia after MI, and modern pharmacological studies have shown that Coptidis Rhizoma and Rhizoma Pinelliae Preparata, the components of LXFG, have antiarrhythmia effects. Here, we investigated whether LXFG can mitigate sympathetic remodeling and suppress arrhythmia and then elucidated its underlying mechanism of action in rats after MI. Sprague-Dawley (SD) rats that had undergone a myocardial infarction model were randomly divided into 6 groups, namely, sham, model, metoprolol, and LXFG groups, with high, medium, and low dosages. We exposed the animals to 30 days of treatment and then evaluated incidence of arrhythmia and arrhythmia scores in vivo using programmed electrical stimulation. Moreover, we determined plasma catecholamines contents via enzyme-linked immunosorbent assay and detected expression of tyrosine hydroxylase (TH) at infarcted border zones via western blot, real-time PCR, and immunohistochemical analyses to assess sympathetic remodeling. Finally, we measured key molecules involved in the NGF/TrKA/PI3K/AKT pathways via western blot and real-time PCR. Compared with the model group, treatment with high dose of LXFG suppressed arrhythmia incidence and arrhythmia scores. In addition, all the LXFG groups significantly decreased protein and mRNA levels of TH, improved the average optical density of TH-positive nerve fibers, and reduced the levels of plasma catecholamines relative to the model group. Meanwhile, expression analysis revealed that key molecules in the NGF/TrKA/PI3K/AKT pathways were downregulated in the LXFG group when compared with model group. Overall, these findings indicate that LXFG suppresses arrhythmia and attenuates sympathetic remodeling in rats after MI. The mechanism is probably regulated by suppression of the NGF/TrKA/PI3K/AKT signaling pathway.

Effect of Hyperbaric Oxygen Therapy on Polarization Phenotype of Rat Microglia After Traumatic Brain Injury.

Background: The neurological defect caused by secondary damage following traumatic brain injury (TBI) is considered critical for the management of TBI. Microglia (MG) are a resident brain macrophage that could differentiate into M1 type or M2 type in response to injury and repair. It is known that the MG transition from M1 phenotype to anti-inflammatory M2 phenotype might reduce secondary injury of TBI. So, a TBI animal model was established and we compared biomarkers of M1 and M2MG between the controls and experimental animals receiving hyperbaric oxygen therapy (HBOT). This study aimed to explore whether HBOT was an effective method to improve neural functional recovery via promoting the polarization of MG into M2 after TBI. Methods: The rats were randomly divided into four groups: SH (Sham-operated), SH + HBO (hyperbaric oxygen), TBI, and TBI + HBO. Each group included 42 rats, and each of these were divided into the following groups: 1, 6, 12, 24, 72 h, 7, and 14 days. The expression of M1 biomarker inducible nitric oxide synthase (iNOS), M2 biomarker arginase 1 (Arg1), associated cytokine tumor necrosis factor-α (TNF-α), and transforming growth factor-ß1 (TGF-ß1) was evaluated after the observation time. Results: TBI significantly increased the expression levels of M1 marker iNOS and M2 markers Arg1 at different time points. The increased expression of iNOS was suppressed, while the expression level of Arg1 was enhanced by HBOT. Moreover, HBOT suppressed the pro-inflammatory TNF-α secreted by M1, and promoting the anti-inflammatory TGF-1ß. Conclusions: In the present study, HBOT showed the effects on shift of M1 toward M2 phenotype with increased expression of M2 biomarkers and decreased expression of M1 biomarkers in the early stage after TBI.

Hyperbaric Oxygen Treatment Improves Intestinal Barrier Function After Spinal Cord Injury in Rats.

Intestinal barrier dysfunction is often observed clinically after spinal cord injury (SCI) and seriously affects long-term quality of life. Hyperbaric oxygen (HBO) treatment has been proved to promote barrier function recovery after injury, but the influence of HBO on intestinal barrier function following SCI is unclear. We aimed to investigate the effect and mechanisms of HBO treatment on intestinal barrier function by measuring the level of tight junction (TJ) proteins and the Ras homolog (Rho)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. SCI model was established in rats, and the animals were randomly assigned into three groups: sham-operation group (SH), SCI group and SCI+HBO group. In the SCI+HBO group, the rats inhaled 100% O2 for 1 h at 2.0 atmospheres absolute pressure (ATA) once per day after surgery. Neurological function and intestinal permeability were assessed after surgery, and the jejunum tissue was excised for histological and intestinal barrier function evaluations. The protein levels of TJ and the Rho/ROCK signaling pathway were also measured. The results showed that in the SCI group, intestinal mucosal injury score, intestinal permeability, and levels of Rho and ROCK1 were higher, and TJ proteins occludin and ZO-1 were lower than those in the SH group (P < 0.01). HBO treatment significantly inhibited the expression of Rho and ROCK1, increased occludin and ZO-1 expression, decreased intestinal permeability, and alleviated intestinal mucosal injury as compared with the SCI group (P < 0.05, P < 0.01). The SCI+HBO group showed higher Basso-Beattie-Bresnahan (BBB) scores relative to the SCI group on postoperative days 7 and 14 (P < 0.01). There was a significant negative correlation between BBB score and intestinal mucosal injury score in rats after HBO treatment (P < 0.05). We concluded from this study that HBO treatment promoted the expression of TJ proteins possibly through inhibiting Rho/ROCK signaling pathway, which protected the intestinal barrier function and improved the intestinal permeability after SCI in rats.

Chang'an II Decoction ( II )-Containing Serum Ameliorates Tumor Necrosis Factor-α-Induced Intestinal Epithelial Barrier Dysfunction via MLCK-MLC Signaling Pathway in Rats.

OBJECTIVE: To investigate the effect of Chang'an II Decoction ( II ))-containing serum on intestinal epithelial barrier dysfunction in rats. METHODS: Tumor necrosis factor (TNF)-α-induced injury of Caco-2 monolayers were established as an inflammatory model of human intestinal epithelium. Caco-2 monolayers were treated with blank serum and Chang'an II Decoction-containing serum that obtained from the rats which were treated with distilled water and Chang'an II Decoction intragastrically at doses of 0.49, 0.98, 1.96 g/(kg·d) for 1 week, respectively. After preparation of containing serum, cells were divided into the normal group, the model group, the Chang'an II-H, M, and L groups (treated with 30 ng/mL TNF-α and medium plus 10% high, middle-, and low-doses Chang'an II serum, respectively). Epithelial barrier function was assessed by transepithelial electrical resistance (TER) and permeability of fluorescein isothiocyanate (FITC)-labeled dextran. Transmission electron microscopy was used to observe the ultrastructure of tight junctions (TJs). Immunofluorescence of zonula occludens-1 (ZO-1), claudin-1 and nuclear transcription factor-kappa p65 (NF-κ Bp65) were measured to determine the protein distribution. The mRNA expression of myosin light chain kinase (MLCK) was measured by real-time polymerase chain reaction. The expression levels of MLCK, myosin light chain (MLC) and p-MLC were determined by Western blot. RESULTS: Chang'an II Decoction-containing serum significantly attenuated the TER and paracellular permeability induced by TNF-α. It alleviated TNF-α-induced morphological alterations in TJ proteins. The increases in MLCK mRNA and MLCK, MLC and p-MLC protein expressions induced by TNF-α were significantly inhibited in the Chang'an II-H group. Additionally, Chang'an II Decoction significantly attenuated translocation of NF-κ Bp65 into the nucleus. CONCLUSION: High-dose Chang'an II-containing serum attenuates TNF-α-induced intestinal barrier dysfunction. The underlying mechanism may be involved in inhibiting the MLCK-MLC phosphorylation signaling pathway mediated by NF-κ Bp65.

Effect of hyperbaric oxygen therapy on HMGB1/NF-κB expression and prognosis of acute spinal cord injury: A randomized clinical trial.

Although there are reports of the beneficial effects of hyperbaric oxygen (HBO) therapy in experimental settings, there are few clinical trials of HBO therapy for acute spinal cord injury (SCI). We investigated the effect of HBO in acute SCI by measuring plasma high mobility group box 1 (HMGB1) and nuclear factor kappa-B (NF-κB) levels, and by monitoring changes in electromyogram F-persistence (the percentage of discernible F-waves) and F-chronodispersion (the difference between minimal and maximal latency). We enrolled 79 acute SCI patients and randomly divided them into control (conventional treatment) and the treatment (conventional treatment plus HBO therapy) groups. Plasma was collected before treatment and after treatment on 1st, 3rd, 7th, 10th and 30th day for the measurement of HMGB1 and NF-κB. Electromyogram F-waves were detected before therapy and after therapy on the 10th and 30th days. Clinical profiles and neurological outcomes were evaluated using American Spinal Injury Association (ASIA) and Frankel Grade scores. Compared to the control group, HBO therapy down-regulated HMGB1 and NF-κB expression in patients with acute SCI on days 3, 7, 10 and 30 (p < 0.05). F-wave chronodispersion decreased at days 10 and 30 (p < 0.01) following HBO. ASIA and Frankel Grade motor/pain scores in the treatment group were significantly improved on day 30 (p < 0.01). There was a positive correlation between plasma NF-κB at day 7 and F-wave dispersion at day 30 (r = 0.76, p = 0.00). In summary, HBO therapy regulated the inflammatory reaction in secondary SCI by decreasing plasma HMGB1/NF-κB levels and reducing the dispersion of electromyogram F-waves of the lower limbs, thereby promoting neurological function recovery.

Shen-ling-bai-zhu-san, a spleen-tonifying Chinese herbal formula, alleviates lactose-induced chronic diarrhea in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-ling-bai-zhu-san (SLBZS) was firstly documented in ancient Chinese medical works "Tai Ping Hui Min He Ji Ju Fang" in Song-dynasty. It has been widely used for treating gastrointestinal disorders such as diarrhea with poor appetite for about 900 years. The present study is to observe the effects of SLBZS on high lactose diet-induced chronic diarrhea. MATERIALS AND METHODS: Rats were subjected to a high lactose diet to induce chronic diarrhea, which were then administrated with SLBZS or smecta. General symptom, body weight, food consumption, water intake and fecal fluid content were recorded every day. The intestinal absorption function was determined by d-xylose uptake assay. The ultrastructures of intestine segments including jejunum, ileum, proximal and distal colon were observed by transmission electron microscopy. Additionally, sodium transport proteins including γ-epithelial sodium channel (ENAC-γ) and sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1) in distal colon were detected by immunohistochemistry and western blotting. RESULTS: Diarrheal rats produced watery or loose, sticky feces, and presented inactiveness and grouping. A high lactose diet caused a significant decline in body weight, serum d-xylose level as well as food consumption rather than water intake. In contrast, general symptoms were improved to a certain extent and body weight loss was alleviated in the rats treated by SLBZS for one week. Fecal fluid content in diarrheal rats treated by SLBZS presented a gradual decrease trend with about 55% in the end, which was significantly less than the model group with about 81%. Meanwhile, SLBZS significantly improved the serum d-xylose level and reversed abnormal changes of tight junctions and microvilli in intestine. Additionally, SLBZS significantly modulated the abnormal expressions of ENAC-γ and ATP1A1 in distal colon of diarrheal rats. CONCLUSIONS: These findings suggested that SLBZS exhibited ameliorating effects against lactose-induced diarrhea, which might be attributed to its modulations on intestinal absorption function as well as mucosal ultrastructure.

The Effect of Tong-Xie-Yao-Fang on Intestinal Mucosal Mast Cells in Postinfectious Irritable Bowel Syndrome Rats.

Objective. To investigate the effects of Tong-Xie-Yao-Fang (TXYF) on intestinal mucosal mast cells in rats with postinfectious irritable bowel syndrome (PI-IBS). Design. PI-IBS rat models were established using a multistimulation paradigm. Then, rats were treated with TXYF intragastrically at doses of 2.5, 5.0, and 10.0 g·kg-1·d-1 for 14 days, respectively. Intestinal sensitivity was assessed based on abdominal withdrawal reflex (AWR) scores and fecal water content (FWC). Mast cell counts and the immunofluorescence of tryptase and c-Fos in intestinal mucosa were measured; and serum IL-1ß, TNF-α, and histamine levels were determined. Results. AWR reactivity and FWC which were significantly increased could be observed in PI-IBS rats. Remarkably increased mast cell activation ratio in intestinal mucosa, together with increased serum TNF-α and histamine levels, could also be seen in PI-IBS rats; furthermore, PI-IBS-induced changes in mast cell activation and level of serum TNF-α and histamine could be reversed by TXYF treatment. Meanwhile, tryptase and c-Fos expression were also downregulated. Conclusion. TXYF improves PI-IBS symptoms by alleviating behavioral hyperalgesia and antidiarrhea, the underlying mechanism of which involves the inhibitory effects of TXYF on activating mucosal mast cells, downregulating tryptase and c-Fos expression, and reducing serum TNF-α and histamine levels.

[Analysis of Animal Modeling Methods for Functional Dyspepsia].

Functional dyspepsia (FD) is a common disease in clinics. It is necessary to establish suitable animal models for clarifying the pathogenesis of FD. FD belongs to "Piman" (abdominal disten- sion) , "Weiwantong" (epigastric pain) , "Caoza" (epigastric upset) in Chinese medicine (CM). It is inor- ganic disease but functional disease. There is no unified standard for FD animal models. Pi deficiency syndrome model is often used as FD animal model now, but they are not completely the same thing. Au- thors summarized and analyzed common methods for FD modeling.

Sini powder () decoction alleviates mood disorder of insomnia by regulating cation-chloride cotransporters in hippocampus.

OBJECTIVE: To investigate the mechanism of Sini Powder () decoction (SND) in the treatment of insomnia. METHODS: The rats were randomly divided into four groups: control, model, SND-treated, and Estazolamtreated groups (n=15 in each group). Sleep deprivation (SD) rat model was established using the modifified multiple platform method for 14 h per day for 14 days, and the behavior of the rats were observed. Na-K-Cl-cotransporter (NKCC1) and K+/Cl- cotransporter (KCC2) in the hippocampus were tested by immunohistochemistry, real-time polymerase chain reaction, and western blot. RESULTS: SD rats displayed anxiety-like behavior, which was alleviated by SND. The protein expressions of NKCC1 and KCC2 in the hippocampus were signifificantly decreased in SD rats compared with those in control rats (P<0.05); these proteins were signifificantly increased by SND (P<0.05). The mRNA expression of KCC2 was signifificantly decreased in SD rats (0.62±0.35 vs. 2.29±0.56; P=0.044), while SND showed a tendency to increase the mRNA of KCC2 in SD rats (P>0.05). By contrast, the mRNA expression of NKCC1 was signifificantly increased in the hippocampus of SD rats (6.58±1.54 vs. 2.82±0.32; P=0.011), while SND decreased the mRNA expression of NKCC1 (6.58±1.54 vs. 2.79±0.81; P=0.016). CONCLUSIONS: Chinese medicine SND could alleviate mood disorder of SD rats by regulating cation-chloride cotransporters, such as NKCC1 and KCC2. These fifindings would have major implications in the mechanism of SND to relieve insomnia.

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome.

AIM: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. METHODS: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1ß and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. RESULTS: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1ß and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1ß and IL-4. CONCLUSION: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

Hyperbaric oxygen intervention reduces secondary spinal cord injury in rats via regulation of HMGB1/TLR4/NF-κB signaling pathway.

BACKGROUND: To investigate whether hyperbaric oxygen (HBO) intervention affects the expressions of inflammatory cytokines, HMGB1/TLR4/NF-κB, and arrests secondary spinal cord injury (SCI). METHODS: One hundred and twenty healthy adult SD rats were randomly divided into four groups: sham, sham + HBO, SCI, and SCI + HBO. Each group was then randomly divided into five subgroups of 6 rats each according to the following time points: 1, 2, 3, 7, and 14 d post injury. Functional recovery of the hindlimb was assessed by Basso, Beattie, and Bresnahan (BBB) scores at different time points after SCI. The expression of HMGB1, TLR4, and NF-κB in the spinal cord tissue was determined by fluorescence quantitative PCR, western blot, immunohistochemistry, and ELISA. RESULTS: The gene expressions of TLR4, HMGB1, and NF-κB (P < 0.01) and the TLR4 protein expression were significantly high after SCI. HBO intervention significantly decreased all the four parameters at 3, 7, and 14 d post injury (P < 0.05). A significant positive correlation (P < 0.01) was observed between the following: HMGB1 mRNA, TLR4 mRNA and TLR4 protein; HMGB1 mRNA and NF-κB mRNA; and TLR4 protein and NF-κB mRNA. BBB score was negatively correlated with HMGB1, TLR4 protein and NF-κB levels. HBO intervention significantly improved the BBB scores at 7 and 14 d post injury (P < 0.05). CONCLUSIONS: Hyperbaric oxygen reduced the expressions of HMGB1, TLR4, and NF-κB and reduced secondary SCI as measured using BBB scores.

Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury.

Hyperbaric oxygen (HBO) therapy is an effective therapy for ischemia/reperfusion (I/R) injury of the brain, small intestine, testes and liver. However, the detailed molecular mechanisms underlying the effect of HBO therapy remain undetermined. In the current study, the hypothesis that preconditioning rats with HBO protects grafted skin flaps against subsequent I/R injury was investigated. In addition, the molecular mechanisms underlying HBO therapy were characterized by analyzing the roles of the following important inflammatory factors: High mobility group protein 1 (HMGB1) and nuclear factor-κ B (NF-κB). A total of 40 rats were randomly divided into the following five groups: (i) Sham surgery (SH); (ii) ischemia followed by reperfusion 3 days following surgery (I/R3d); (iii) ischemia followed by reperfusion 5 days following surgery (I/R5d); (iv) HBO preconditioning (HBO-PC) and ischemia followed by reperfusion 3 days following surgery (HBO-PC+3d); and (v) HBO-PC and ischemia followed by reperfusion 5 days following surgery (HBO-PC+5d). For the surgical procedure, all pedicled skin flaps were first measured and elevated (9x6 cm). The feeding vessels of the skin flaps were subsequently clamped for 3 h and released to restore blood flow. The rats in the HBO-PC+3d and HBO-PC+5d groups received 1 h HBO for 3 and 5 consecutive days, respectively, prior to surgery. Following surgery, the rats were euthanized, and grafted tissues were collected for western blotting and immunohistochemistry. HBO-PC increased blood perfusion in epigastric skin flaps and attenuated I/R injury following skin flap graft. Additionally, the elevated expression of HMGB1 and NF-κB proteins during I/R injury was attenuated by HBO-PC treatment. HBO-PC may therefore be applied to reduce I/R injury and improve the survival rate of grafted skin flaps. The molecular mechanisms underlying the effect of HBO therapy are associated with the attenuation of inflammatory responses.

Effects of hyperbaric oxygen on MMP-2 and MMP-9 expression and spinal cord edema after spinal cord injury.

AIMS: To evaluate the effects of hyperbaric oxygen (HBO) therapy on MMP-2 and MMP-9 expression and spinal cord edema after acute spinal cord injury (SCI). MAIN METHODS: Ninety-six healthy adult Sprague − Dawley rats were randomly divided into 4 groups: sham, sham + HBO, SCI, and SCI + HBO. Each group was subdivided into 4 subgroups of 6 rats each: 24 h, 48 h, 72 h, and 5 d post-injury. The expression levels of matrix metalloproteinase-2 (MMP-2), MMP-9, interleukin (IL-6), and vascular endothelial growth factor (VEGF) were measured using ELISA. The water content of the spinal cord was also measured by Elliot equation. KEY FINDING: MMP-2 and MMP-9 levels and spinal cord water content increased significantly in the SCI group compared to those in the sham and sham + HBO groups at different time points after SCI (P < 0.01). The MMP-2 level was significantly different between the SCI and SCI + HBO groups at 72 h after SCI (P < 0.05), while the MMP-9 level was significantly different at 48 h, 72 h, and 5 d (P < 0.05). The water content of the spinal cord was significantly higher in the SCI group at 5 d after SCI (P < 0. 01). MMP-2 (P < 0.05) and MMP-9 (P < 0.01) levels were positively correlated with spinal cord water content. SIGNIFICANCE: HBO reduced SCI-induced spinal cord edema, stabilized the blood-spinal cord barrier, and promoted recovery of neuronal function by down regulating the expression of IL-6, MMP-2, and MMP-9 and up regulating the expression of VEGF.