Gentianella turkestanerum Showed Protective Effects on Hepatic Injury by Modulating the Endoplasmic Reticulum Stress and NF-κB Signaling Pathway

2019 ◽  
Vol 19 (6) ◽  
pp. 452-460
Author(s):  
Jianhua Yang ◽  
Dandan Zhu ◽  
Limei Wen ◽  
Xueying Xiang ◽  
Junping Hu
Keyword(s):  
Endoplasmic Reticulum ◽  
Mtt Assay ◽  
Nuclear Translocation ◽  
Control Group ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Protective Effects ◽  
Blank Control Group ◽  
Caspase 12 ◽  
Cellular Apoptosis

Objective: To investigate the protective effects of Gentianella turkestanerum extraction by butanol (designated as GBA) on hepatic cell line L02 injury induced by carbon tetrachloride (CCl4) and hydrogen peroxide (H2O2). Methods: L02 cells were incubated with 5 µg/mL, 10 µg/mL, 20 µg/mL, 40 µg/mL, 60 µg/mL, 80 µg/mL and 100 µg/mL GBA for 24 hours, and then MTT assay was used to screen the cytotoxicity for GBA. Cells were divided into blank control group, CCl4/H2O2 model group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L); silymarin+CCl4/H2O2 group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L) and 5 µg/mL silymarin; GBA+CCl4/H2O2 group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L) and GBA (5 µg/mL, 10 µg/mL and 20 µg/mL). MTT assay was performed to determine the cellular activity. Malondialdehyde (MDA) content was determined using a commercial kit. The alanine transaminase (ALT), aspartate transaminase (AST) in the supernatant was determined. PE-Annexin V/7-ADD method was utilized to determine the apoptosis of cells. RT-PCR was used to evaluate the expression of endoplasmic reticulum stressrelated genes (CHOP, PERK, IRE1 and ATF6) mRNA. Western blot analysis was performed to determine the expression of CHOP, Caspase 12 and NF-κB protein. Results: Cellular survival after GBA (5 µg/mL, 10 µg/mL and 20 µg/mL) incubation was ≥ 75%. After GBA incubation, levels of ALT and AST showed a significant decrease (P < 0.05), while that of the MDA showed a significant decrease (P < 0.05). The apoptosis in the CCl4 or H2O2 group showed a significant increase compared to the control group (P < 0.05). In contrast, GBA-preincubation could attenuate the cellular apoptosis compared to the CCl4 or H2O2 group, which displayed a dose-dependent manner (P < 0.05). The expression of CHOP, PERK, IRE1 and ATF6 mRNA was significantly up-regulated in the presence of CCl4 or H2O2 (P < 0.05). Whereas, GBA induced a significant decrease in these mRNA thereafter (P < 0.05), together with a decrease in CHOP and Caspase 12 proteins (P < 0.05). Besides, it could attenuate the expression of NF-κB p65 in nuclear protein. Conclusions: G. turkestanerum could inhibit the lipid peroxidation and increase the antioxidant activity. Also, it could inhibit the cellular apoptosis through down-regulating the transcriptional level of ERS related genes and proteins. This process was associated with the nuclear translocation of NF-κB p65 protein.

scholarly journals Effects of Lentinan on Endothelial Cell Activity, Inflammatory Response, Endoplasmic Reticulum Stress, and Apoptosis in Sepsis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yan Xu ◽  
Yeping Du
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Activity ◽  
Sepsis Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Protective Effects

The aim of this study is to explore the protective effects of lentinan on endoplasmic reticulum stress, inflammation, and apoptosis in sepsis endothelial cells. Firstly, lentinan was extracted, purified, and analyzed. When the concentration of lentinan was in the range of 0.04–4 μM, there was no obvious effect on the morphology of HUVECs. When the concentration reached 10 M, the cells were obviously contracted and necrotic. CCK-8 cell activity experiment showed that when the concentration of lentinan reached 4 μM, the cell activity decreased significantly (P<0.001), and it was in a dose-dependent manner. Then, the cells were divided into the control group (0 μM lentinan), sepsis group, sepsis + lentinan 1.2 μM group, and sepsis + lentinan 2 μM group. Enzyme-linked immunosorbent assay showed that lentinan could significantly reduce the expression of TNF-α, IL-1β, and IL-6 in sepsis endothelial cells (P<0.001). In addition, flow cytometry and TUNEL staining showed that compared with the control group, the apoptosis of cells in the sepsis group increased significantly (P<0.001), and lentinan could inhibit apoptosis (P<0.001). In terms of mechanism research, the mRNA and protein expression of endoplasmic reticulum stress-related protein in endothelial cells were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting, respectively. It was found that the expression of SIRT1, the upstream factors of endoplasmic reticulum stress in sepsis cells, was obviously inhibited (P<0.001), and the expression of CHOP, GRP78, IRE1α, and ATF6 was significantly increased (P<0.001), However, the pretreatment of lentinan could significantly reverse the above changes (P<0.001). Besides, lentinan could also reduce the expression of phosphorylated p65 protein (the activation marker of NF-κb) and iNOS. Conclusion. When sepsis occurs, lentinan can protect endothelial cells from ERS inflammation and apoptosis induced by sepsis. Thus, lentinan is expected to be a new target for the treatment of sepsis-induced endothelial damage.

Effect of Curculigo orchioides on Reflux Esophagitis by Suppressing Proinflammatory Cytokines

2012 ◽  
Vol 40 (06) ◽  
pp. 1241-1255 ◽  
Author(s):  
Sae-Kang Ku ◽  
Jae-Soo Kim ◽  
Young-Bae Seo ◽  
Yong-Ung Kim ◽  
Seung-Lark Hwang ◽  
...  
Keyword(s):  
Reflux Esophagitis ◽  
Group Treatment ◽  
Control Group ◽  
Esophageal Mucosa ◽  
Dependent Manner ◽  
Protective Effects ◽  
Model Group ◽  
Curculigo Orchioides ◽  
Intact Group ◽  
Tnf Α

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling

2021 ◽  
Author(s):  
Lingfeng Qin ◽  
Haifeng Zhang ◽  
Busu Li ◽  
Quan Jiang ◽  
Francesc Lopez ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Fluorescein Isothiocyanate ◽  
The Body ◽  
Blue Dye ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Cavernous Malformations ◽  
Morphological Alterations ◽  
The Brain

Objective: Cerebral cavernous malformations (CCMs) can happen anywhere in the body, although they most commonly produce symptoms in the brain. The role of CCM genes in other vascular beds outside the brain and retina is not well-examined, although the 3 CCM-associated genes ( CCM1 , CCM2 , and CCM3 ) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in lymphatics. Approach and Results: Mice with an inducible pan–endothelial cell (EC) or lymphatic EC deletion of Ccm3 ( Pdcd10 ECKO or Pdcd10 LECKO ) exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure. Morphological alterations were correlated with lymphatic dysfunction in Pdcd10 LECKO mice as determined by Evans blue dye and fluorescein isothiocyanate(FITC)-dextran transport assays. Pdcd10 LECKO lymphatics had increased VEGFR3 (vascular endothelial growth factor receptor-3)-ERK1/2 signaling with lymphatic hyperplasia. Mechanistic studies suggested that VEGFR3 is primarily regulated at a transcriptional level in Ccm3-deficient lymphatic ECs, in an NF-κB (nuclear factor κB)–dependent manner. CCM3 binds to importin alpha 2/KPNA2 (karyopherin subunit alpha 2), and a CCM3 deletion releases KPNA2 to activate NF-κB P65 by facilitating its nuclear translocation and P65-dependent VEGFR3 transcription. Moreover, increased VEGFR3 in lymphatic EC preferentially activates ERK1/2 signaling, which is critical for lymphatic EC proliferation. Importantly, inhibition of VEGFR3 or ERK1/2 rescued the lymphatic defects in structure and function. Conclusions: Our data demonstrate that CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM.

Autophagy triggers endoplasmic reticulum stress and C/EBP homologous protein-mediated apoptosis in OGD/R-treated neurons in a caspase-12-independent manner

2021 ◽  
Author(s):  
Ying Tian ◽  
Liang Wang ◽  
Zhiqiang Qiu ◽  
Yulun Xu ◽  
Rongrong Hua
Keyword(s):  
Endoplasmic Reticulum ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Homologous Protein ◽  
Caspase 12 ◽  
Induced Apoptosis

We reported that a high level of autophagy was initiated by oxygen-glucose deprivation (OGD) and was maintained in neurons even after oxygen-glucose deprivation followed by reoxygenation (OGD/R), accompanied by neuronal apoptosis. This study focused on autophagy-induced apoptosis and its signaling network, especially the role of endoplasmic reticulum stress (ERS). Analysis of primary cultured cortical neurons from mice showed that the autophagy-induced apoptosis depended on Caspase-8 and -9 but not Caspase-12. This finding did not mean that the endoplasmic reticulum did not participate in this process. Increases in the levels of endoplasmic reticulum (ER) biomarkers and Binding immunoglobulin protein (BiP) were induced by autophagy in OGD/R-treated neurons. In addition, as an apoptotic transcription factor induced by ER stress, C/EBP homologous protein (CHOP) expression was significantly increased in neurons after OGD/R. This result suggested that the autophagy-Bip-CHOP-caspase (8 and 9)-dependent apoptotic signaling pathway at least partly participated in autophagy-induced apoptosis in primary cortical neurons. It revealed that ER induced apoptosis in neurons suffering from OGD/R injury in an ER stress-CHOP-dependent manner rather than a caspase-12-dependent manner. However, more research on signaling or cross-linking networks and intermediate links are needed. The realization of caspase-12-independent BiP-CHOP neuronal apoptosis pathway has expanded our understanding of the neuronal apoptosis network, which may eventually provide endogenous interventional strategies for OGD/R injury after stroke.

224 A GROWTH OF HUMAN BG-1 CANCER CELLS EXPRESSING ESTROGEN RECEPTORS WAS ENHANCED BY SYNTHETIC PYRETHROIDS, LAMBDA-CYHALOTHRIN AND CYPERMETHRIN, VIA AN ESTROGEN RECEPTOR-DEPENDENT SIGNALING PATHWAY

2015 ◽  
Vol 27 (1) ◽  
pp. 201 ◽  
Author(s):  
C.-W. Kim ◽  
R.-E. Go ◽  
K.-C. Choi
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Ovarian Cancer Cells ◽  
Transcriptional Level ◽  
Synthetic Pyrethroids ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Pyrethroid Insecticides ◽  
Lambda Cyhalothrin

Synthetic pyrethroids (SP) are the most common pesticides in recent use, which are used as indoor pest control. The widespread use of SPs has resulted in extensive exposure to wildlife and human. Recently some SPs are suspected as endocrine disrupting chemicals (EDC) and have been assessed for their potential estrogenicity by various assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LCT) and cypermethrin (CP), the most commonly used pyrethroid insecticides in Korea, using BG-1 ovarian cancer cells expressing oestrogen receptors (ER). To evaluate the estrogenic activities of two SPs, LCT and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT–PCR). In MTT assay, LCT (10–6 M) and CP (10–5 M) significantly induced the growth of BG-1 cancer cells, 1.61 ± 0.1 and 1.45 ± 0.06 times, respectively, as 17β-oestradiol (E2, 10–9 M, 2.73 ± 0.25 times) did. LCT or CP-induced cell growth was reversed to a control level (DMSO) by addition of ICI 182 720 (10–8 M), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT–PCR results showed that transcriptional level of ERα expression was significantly down-regulated by LCT and CP as in case of E2. Taken together, these results indicate that LCT and CP may possess estrogenic potentials to stimulate ovarian cancer cells expressing ERs via an ER-dependent manner, and these collective results confirm the carcinogenicity of these SP, LCT and CP, in ER-positive cells or tissues.

scholarly journals Epimedium Polysaccharide Ameliorates Benzene-Induced Aplastic Anemia in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jin He ◽  
Ru Han ◽  
Gongchang Yu ◽  
Martin F. Lavin ◽  
Qiang Jia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Immune Modulation ◽  
Mononuclear Cells ◽  
Peripheral Blood Cell ◽  
Environmental Pollutant ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Protective Effects

Benzene (BZ) is an important occupational and environmental pollutant. Exposure to BZ may cause aplastic anemia which is characterized as bone marrow hematopoietic failure. In order to reduce the harmful effects of this pollutant, it is necessary to identify additional preventative measures. In this study, we investigated the protective effects of epimedium polysaccharide (EPS), a natural compound with antioxidant and immune-enhancing potency, on aplastic anemia induced by benzene exposure in mice. Male CD-1 mice were randomly divided into five groups including control, BZ (880 mg/kg), LE (EPS low-dose, 20 mg/kg + BZ), ME (EPS middle-dose, 100 mg/kg + BZ), and HE (EPS high-dose, 200 mg/kg + BZ) groups. Animals were exposed to BZ by subcutaneous injection in the presence or absence of EPS via oral administration. All mice were treated 3 times a week for 8 consecutive weeks to develop a mouse model of benzene-induced aplastic anemia (BIAA). Results showed that BZ induced a significant decrease in both white and red blood cells, platelet counts, and hemoglobin level compared with that in the control group (p<0.01). Treatment of EPS led to a protective effect against these changes particularly in the highest-dose group (HE, p<0.01). EPS also recovered the decreased number of nucleated cells in peripheral blood cell smears and femur biopsies by BZ exposure. The increased level of reactive oxygen species (ROS) in bone marrow mononuclear cells (BMMNCs) in mice from the BZ group was significantly lower (p<0.01) in the mice from the highest concentration of EPS (HE) group when compared with that from the control group. In addition, BZ exposure led to a significant increase in the apoptosis rate in BMMNCs which was prevented by EPS in a dose-dependent manner (p<0.01). The antiapoptosis effect of EPS was through reversing apoptotic proteins such as BAX, Caspase-9 and Caspase-3, and Bcl-2. Finally, EPS treatment partially restored the levels of T cells and the different subtypes except CD80+ and CD86+ compared with the BZ group (HE, p<0.05). These results suggest that EPS has protective effects against BIAA via antioxidative stress, immune modulation, and antiapoptosis mechanisms.

scholarly journals Sanbai Melon Seed Oil Exerts Its Protective Effects in a Diabetes Mellitus Model via the Akt/GSK-3β/Nrf2 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Fang Wang ◽  
Yuanhang Xi ◽  
Wenzhe Liu ◽  
Jie Li ◽  
Ya Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Seed Oil ◽  
Nuclear Translocation ◽  
Tissue Injury ◽  
Antidiabetic Activity ◽  
Dependent Manner ◽  
Protective Effects ◽  
Nrf2 Pathway ◽  
Melon Seed ◽  
Melon Seed Oil

Traditional Chinese medicine (TCM) plays an important role in the treatment of type 2 diabetes mellitus (T2DM). However, the lack of adequate and scientifically rigorous evidence has limited its application in this disorder. Sanbai melon seed oil (SMSO) is used in folk medicine to treat DM; however, only few literature reports exist regarding its mechanism. Herein, we aimed to confirm the antidiabetic activity of SMSO in a T2DM model and further elucidate its possible mechanisms. The T2DM rat model was induced by high-fat and sugar diet and streptozocin (STZ, 40 mg/kg). SMSO was administered at doses of 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg. Several biochemical parameters and antioxidant protein levels were measured to evaluate the hyperglycemic and antioxidant activities of SMSO. Western blotting was performed to determine its potential mechanism. Based on the results, SMSO treatment significantly reduced blood glucose levels, increased plasma insulin, and repaired islet tissue injury in diabetic rats (P<0.05). To add, it markedly reduced MDA levels and increased that of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Western blot results showed that SMSO induced n-Nrf2 and HO-1 expression and Akt and GSK-3β phosphorylation in a dose-dependent manner. Further studies showed that LY294002, aPI3K inhibitor, abolished the effects of SMSO on GSK-3β phosphorylation and Nrf2 nuclear translocation as well as the protective effects on pancreatic β cells. Together, these results suggest that SMSO regulates the Akt/GSK-3β/Nrf2 pathway and induces the expression of antioxidant proteins to impede oxidative stress in rats with T2DM.

scholarly journals In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 478 ◽  
Author(s):  
Rasha Al-Rikabi ◽  
Hanady Al-Shmgani ◽  
Yaser Hassan Dewir ◽  
Salah El-Hendawy
Keyword(s):  
Breast Cancer ◽  
Chromatin Condensation ◽  
Control Group ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mcf7 Cells ◽  
Tnf Α

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.

Protective effects of forced exercise against nicotine-induced anxiety, depression and cognition impairment in rat

2016 ◽  
Vol 27 (1) ◽  
Author(s):  
Majid Motaghinejad ◽  
Sulail Fatima ◽  
Morteza Karimian ◽  
Saeid Ganji
Keyword(s):  
Motor Activity ◽  
Forced Swim Test ◽  
Nicotine Withdrawal ◽  
Male Rats ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Dependent Manner ◽  
Protective Effects ◽  
Cognition Impairment ◽  
Anxiety Depression

AbstractNicotine is one of the psychostimulant agents displaying parasympathomimetic activity; the chronic neurochemical and behavioral effects of nicotine remain unclear. Exercise lowers stress and anxiety and can act as a non-pharmacologic neuroprotective agent. In this study, the protective effects of exercise in nicotine withdrawal syndrome-induced anxiety, depression, and cognition impairment were investigated.Seventy adult male rats were divided randomly into five groups. Group 1 served as negative control and received normal saline (0.2 mL/rat, i.p.) for 30 days, whereas group 2 (as positive control) received nicotine (6 mg/kg/day, s.c.) for the first 15 days. Groups 4, 5, and 6 were treated with nicotine (6 mg/kg/day, s.c.) for the first 15 days and then were treated with forced exercise, bupropion (20 mg/kg/day, i.p.), or a combination of the two for the following 15 days. Between day 25 and day 30, Morris water maze was used to evaluate spatial learning and memory. From days 31 to 35, the elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were used to investigate the level of anxiety and depression in the subjects.Nicotine-dependent animals indicated a reflective depression and anxiety in a dose-dependent manner in FST, EPM, and TST, which were significantly different from the control group and also can significantly attenuate the motor activity and anxiety in OFT.Forced exercise, bupropion, or their combination can attenuate nicotine cessation-induced anxiety, depression, and motor activity in the mentioned behavioral assay. We conclude that forced exercise can protect the brain against nicotine withdrawal-induced anxiety, depression, and cognitive alteration.

scholarly journals The Protective Effects of Chronic Intermittent Hypobaric Hypoxia Against Osteoarthritis in Rats - Role of Nitric Oxide

2021 ◽  
Author(s):  
Tianci Wang ◽  
Dong Ren ◽  
Yunshan Su ◽  
Jian Lu ◽  
Ming Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hypobaric Hypoxia ◽  
Meniscal Tear ◽  
Cartilage Degeneration ◽  
Joint Fluid ◽  
Control Group ◽  
No Production ◽  
Protective Effects ◽  
Blank Control Group ◽  
Intermittent Hypobaric Hypoxia

Abstract The study explored the effect of chronic intermittent hypobaric hypoxia (CIHH) on osteoarthritis (OA). CIHH conditioning was realized by exposing rats to hypobaric hypoxia environment mimicking 5,000 m high-altitude (PB=404 mmHg, PO2=84 mmHg) 6 h per day, once daily for 28 days. OA model was induced by surgically-induced medial meniscal tear. Male Wistar rats were randomly assigned into 5 groups: preconditioning group （CIHH + OA）, postconditioning group （OA + CIHH）, control group, inhibitor group [OA + inducible nitric oxide synthase (iNOS) inhibitor], blank control group. The expression iNOS, nitric oxide (NO) content levels in the joint fluid were measured at 1, 2, 3 weeks after the OA modelling. Results revealed that OA modelling induced cartilage degeneration, up-regulated iNOS expression, increased joint fluid NO content. CIHH preconditioning and postconditioning reduced cartilage degeneration, prevented the NO production. Inhibitor groups showed alleviated joint degeneration than control group, but not as effective as CIHH condition. These results suggest that both CIHH preconditioning and postconditioning plays a protective role on OA, one of the mechanism was inhibiting the overexpression of iNOS and NO production.

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