Therapeutic Effect and Antioxidant Mechanism of Xiaochuanning Granule on Psychological Stress Related Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect and antioxidant mechanism of Xiaochuanning granule on psychological stress-related asthma in rats. MethodThe 6-week-old male SD rats were randomly divided into the normal group， asthma group， stress group， stress-related asthma group， western medicine group （atomization of budesonide suspension） and traditional Chinese medicine （TCM） group （Xiaochuanning granule 2.48 g·kg-1）. The asthma model was established during 28 days by intraperitoneal injection of 10% ovalbumin（OVA）on the 1st and 8th days and inhaling of vapourized 1% OVA started at the 15th day. Stress group， stress-related asthma group， western medicine group and TCM group were given restraint stimulation during the 28 days to establish the psychological stress-related asthma model. Rats in each group were administered with corresponding drug for 14 days from the 15th day. The sucrose preference test and open field test were performed at the 15th and 28th days. At the end of experiment， the body weight， serum interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） levels， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione （GSH） in lung tissues were detected by assay kits. Hematoxylin-eosin（HE） staining was conducted to observe the pathological changes in lung tissues. Meanwhile， Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and hemeoxygenase-1 （HO-1） in lung tissues. ResultCompared with the stress-related asthma group， the body weight， sugar water consumption rate and open field distance in the TCM group were significantly increased （P<0.05）， and the serum IL-4， IL-5， IL-13 levels were significantly decreased （P<0.05）， the levels of SOD and GSH in lung tissues increased significantly （P<0.05）， while the level of MDA decreased significantly （P<0.05）. HE staining showed that the bronchial mucosal injury， inflammatory cell infiltration， gland hyperplasia， epithelial degeneration and necrosis were significantly ameliorated in the TCM group than in the stress-related asthma group. The expression of Nrf2 and HO-1 protein in lung tissues also increased significantly （P<0.05）. ConclusionXiaochuanning Granule can regulate the psychological stress state of stress-related asthmatic rats， alleviate airway inflammatory reaction， and suppress oxidation， which is related to its up-regulation of the Nrf2/HO-1 protein expression.

Effects of suspended leukocyte depleted red blood cell infusion on HO-1 expression and T lymphocyte subsets in peripheral blood of patients with MDS / 中国医师进修杂志

Objective:To investigate the effect of suspended leukocyte poor red blood cell transfusion on hemeoxygenase-1 (HO-1) expression and T lymphocyte subsets in peripheral blood of patients with myelodysplastic syndrome.Methods:50 cases of MDS patients treated in Shandong Blood Center from January 2016 to December 2019 were selected as the research object. According to the different infusion of blood components, they were randomly divided into the observation group and the control group, with 25 cases in each group.The patients in the observation group were treated with s suspended leukocyte poor red blood cell transfusion, and the patients in the control group were treated with washing red blood cell infusion.The level of HO-1, interleukin-6 (IL-6) and TNF-α and the T cell subset such as CD 3+, CD 4+, CD 8+ and CD 4+/CD 8+ in the serum before and after transfusion were tested by enzyme linked immunosorbent assay and flow cytometry, respectively. Results:There was no statistically significantdifference in the level of HO-1, IL-6 and TNF-α in the serum of the two groups before transfusion ( P>0.05); After transfusion, TNF-α in the serum of the observation group significantly decreased, compared with that in control group: (152.10 ± 21.89) ng/L vs. (201.14 ± 28.90) ng/L, (1.34 ± 0.45) ng/L vs. (2.89 ± 1.01) ng/L. However, the HO-1 significantly increased: (78.91 ± 15.74) μg/L vs. (58.99 ± 13.33) μg/L, andthe difference was statistically significant ( P<0.05). There was nostatistically significantdifference in the immunologic functions of the two groups before transfusion ( P>0.05); After transfusion, CD 4+/CD 8+of the observation group both significantly increased, compared with that inthe control group: (49.11 ± 19.13)% vs. (47.13 ± 12.84)%, (25.23 ± 10.80)% vs. (21.09 ± 12.28)%, (24.74 ± 10.84)% vs. (21.88 ± 11.18)%, 1.02 ± 0.25 vs. 0.96 ± 0.20, and the difference was statistically significant ( P<0.05). Conclusions:The expression level of HO-1 in peripheral blood and immune function of patients with myelodysplastic syndrome can be improved by suspended leukocyte poor red blood cell transfusion.

Hydrogen sulfide protects intestinal mucosa in a neonatal rat model of necrotizing enterocolitis by upregulating the expression of HO-1 / 临床儿科杂志

Objective To explore the protective effects of GYY4137, a new hydrogen sulfide donor, on intestinal mucosa in a neonatal rat model of necrotizing enterocolitis (NEC), and its potential mechanism.Methods Sixty SD rats were randomly assigned into 4 groups: group A (control group), group B (NEC group), group C (NEC with GYY4137 treatment, H2S donor group), and group D (NEC with GYY4137 and Znpptreatment, HO-1 inhibitor group). The SD rat models of NEC were established using simulated milk feeding-hypoxia-cold stress-Lipopolysaccharides. The injury degree of intestinal mucosa was evaluated using HE-staining, and its mechanisms were investigated using biochemical indicators and Western blotting. Results Compared with control group, the pathology score and the total superoxide dismutase (T-SOD) in the NEC group was significantly higher, the concentrations of methane dicarboxylic aldehyde (MDA) and necrosis factor α (TNF-α) were lower(P<0.05). Compared with those in NEC group, the pathology score and the concentration of MDA and TNF-α in the H2S donor group were signiflcantly lower, the T-SOD, and the HO-1 expression was higher. The pathology score and the level of MDA and TNF-α were signiflcantly increased after treated with HO-1 inhibitor Znpp, and T-SOD was signiflcantly decreased.. Conclusions The GYY4137, as a new H2S donor, could attenuate the injury of intestinal mucosa in a neonatal rat model of NEC by upregulating the expression of HO-1.

Cobalt Chloride Attenuates Oxidative Stress and Inflammation through NF-kappaB Inhibition in Human Renal Proximal Tubular Epithelial Cells

We evaluated the effect of cobalt chloride (CoCl2) on TNF-alpha and IFN-gamma-induced-inflammation and reactive oxygen species (ROS) in renal tubular epithelial cells (HK-2 cells). We treated HK-2 cells with CoCl2 before the administration of TNF-alpha/IFN-gamma. To regulate hemeoxygenase-1 (HO-1) expression, the cells were treated CoCl2 or HO-1 siRNA. CoCl2 reduced the generation of ROS induced by TNF-alpha/IFN-gamma. TNF-alpha/IFN-gamma-treated-cells showed an increase in the nuclear translocation of phosphorylated NF-kappaBp65 protein, the DNA-binding activity of NF-kappaBp50 and NF-kappaB transcriptional activity and a decrease in IkappaBalpha protein expression. These changes were restored by CoCl2. We noted an intense increase in monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES) production in TNF-alpha/IFN-gamma-treated cells. We demonstrated that this effect was mediated through NF-kappaB signaling because an NF-kappaB inhibitor significantly reduced MCP-1 and RANTES production. CoCl2 effectively reduced MCP-1 and RANTES production. The expression of HO-1 was increased by CoCl2 and decreased by HO-1 siRNA. However, knockdown of HO-1 by RNA interference did not affect MCP-1 or RANTES production. We suggest that CoCl2 has a protective effect on TNF-alpha/IFN-gamma-induced inflammation through the inhibition of NF-kappaB and ROS in HK-2 cells. However, CoCl2 appears to act in an HO-1-independent manner.

Effect of transducted heme oxygenase-1 protein on rat brain ischemia-reperfusion injury / 中国药理学通报

Aim To investigate the effect of transduct-ed-hemeoxygenase-1 ( HO-1 ) protein on brain ischemi-a-reperfusion ( I/R ) rat hippocampal neurons injury. Methods 11 R ( arginine residues )-fused HO-1 pro-tein was established and 50 male Mongolian gerbils were randomly divided into 5 groups ( n=10 ):I/R ( control group ) , I/R + 5 mg · kg-1 saline group ( group S ) , I/R + 5 mg · kg-1 11 R group ( group R), I/R + 5mg·kg-1 11R-HO-1 group (group H1) and I/R + 25 mg · kg-1 11 R-HO-1 group ( group H2). For I/R experiments, ischemia was induced for 5 min by occluding the common carotid arteries bilater-ally with aneurysm clips under Ketamine anesthesia. The experiment was conducted after the neurons were intraperitoneally injected with 5mg·kg-1 saline,11R , 11R-HO-1,or 25mg · kg-1 11R-HO-1 for 3 h. The rats were killed after 24h of reperfusion. Hippocampus was removed immediately for determination of cAMP level, neuronal apoptotic rate, and expression of HO-1 and Caspase-3 protein, mitochondria was observed un-der electron microscope. Results Among group C, group S and group R,there were no differences in the expressions of HO-1, Caspase-3 protein, cAMP level , neuronal apoptotic rate and mitochondria damage ( P>0. 05). Compared with group C, group S and group R, the expression of HO-1 protein was up-regulated, the expression of Caspase-3 protein was down-regula-ted, cAMP level increased, the apoptotic rate was sig-nificantly decreased and mitochondria damage de-creased in group H1 ( P < 0. 01 ) . Compared with group H1 , the expression of HO-1 protein was up-regu-lated, the expression of Caspase-3 protein was down-regulated, cAMP level increased, the apoptotic rate was significantly decreased and mitochondria damage decreased in group H2 ( P <0. 01 ) . Conclusion Transducted-HO-1 protein can attenuate brain ischemi-a-reperfusion rat hippocampal neurons injury.

A mycoplasma lipopeptide induces hemeoxygenase-1 expression via TLR2, 6/c-Src/PI3 K pathway in monocytes / 中国免疫学杂志

Objective:To observe the molecular mechanism involved in expression of hemeoxygenase -1 (HO-1) induced by a macrophage-activating lipopeptide-2 (MALP-2).Methods:THP-1 cells were cultured in vitro and stimulated by MALP-2 for 12 h, expression of HO-1 was detected by Western blot .TLR2 and TLR6 neutralizing antibodies incubation , dominant negative plasmids transfection were used to assess the functional of TLR 2,6 in mediating HO-1 expression.Phosphorylation of c-Src and Akt were detec-ted by Western blot, and c-Src siRNA and PI3K inhibitor LY294002 were used to investigate the role of c-Src and PI3K in HO-1 ex-pression.Results:MALP-2 induced c-Src phosphorylation , and TLR2 and TLR6 neutralizing antibodies , or their dominant negatively plasmids could abrogate this effect .In addition, siRNA of c-Src could decrease the phosphorylation level of Akt , and the PI3K inhibi-tor could inhibit HO-1 expression.Conclusion: MALP-2 can induce THP-1 cells expression of HO-1 through TLR2,6/c-Src/PI3K pathways .

Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

Active effect of hemeoxygenase-1 expression on Chang liver cell induced by inorganic arsenic / 中国地方病学杂志

Objective To observe whether sodium arsenite(NaAsO2)can activate the expressions of hemeoxygenase-1(HO-1)of normal human liver cell line named Chang liver.Methods Chang liver cells were exposed to NaAsO2 at 10 μmoL/L,0(contml),2,6,12,24 h and at 0(control),5,10,25,50 μmol/L in 12 h, followed by the measuring of the expressions of HO-1 protein in ceUs with western blot.Results In 10 μmol/L groups Chang liver cells exposed for 6,12,24 h cultured in vitro,the expressions of HO-l protein(3.97±0.72, 12.92±2.98,23.29±3.82)was significantly higher than that of control(1.00±0.00),and compared with the control, the difference being statistically significant(F=85.83,P＜0.01;t=-9.42,-8.95,-13.83,respectively,P＜ 0.05 or＜0.01).In 12 h,5,10,25 and 50 μmol/L groups cultured in vitro,the expressions of HO-1(16.34±0.25, 7.75±0.39,7.93±0.14,12.48±0.35)was significantly higher than that of control(1.00±0.00).and compared with the control,the difference being statistically significant(F=85.83,P＜0.01;t=-36.25,-30.19,-86.40, -56.40,respectively,all P＜0.01).Conclusion Inorganic arsenic call induce the activation of HO-1,promote the expression of protein in a time-and dose-dependent manner.

Expression of heme oxygenase-1 in peritoneal metastasis of gastric cancer and its significance HUI / 中华消化杂志

Objective To investigate the expression and significance of heme oxygenase-1(HO-1) in gastric adenocarcinoma and its peritoneal metastatic tissues, as well as drug-resistant cell strains. Methods The expression of HO-1 in patients with (n=68) or without (n=46) peritoneal metastasis of gastric adenocarinoma was examined. The expression of HO-1 in cancerous tissue, peritoneal metastatic foci, and normal peritoneum was detected by immunohistochemistry. The expression of HO-1 protein in metastatic foci and drug-resistant cell strains was measured by Western blotting. Results The positive expression of HO-1 was 39.7% (27/68) in gastric adenocarcinoma tissues with metastasis and 41.2% (28/68) in peritoneal metastatic tissues, which was significantly higher than that in normal peritoneum (0%,0/68,P<0.01) and gastric adenocarcinoma tissues without metastasis (21.7%, 10/46, P<0.05). The Western blot study showed that the HO-1 expression in metastatic tissues was higher than that in normal peritoneum (P<0.05). The expression of HO-1 protein was markedly increased in GC9811-P drug-resistant cell strains compared with its parental cell strains (P<0.05). Conclusions The increased expression of HO-1 may be involved in the peritoneal metastasis of gastric adenocarcinoma, and related to the malignant potential. The underlying signal pathways in neopastic epithelium may also be related to the multi-drug resistance.

Effects of L-tetrahydropalmatine on hemeoxygenase-1 in cerebral tissue of rats and endogenous carbon monoxide during global cerebral ischemia/reperfusion / 中国中西医结合急救杂志

Objective: To observe the changes of hemeoxygenase-1 (HO-1) activity in cerebral tissue, carboxyhemoglobin (COHb) level in blood of rats during global cerebral ischemia/reperfusion (I/R) and the influence of L-tetrahydropalmatine (L-THP) on them. Methods: Seventy-seven Sprague-Dawley (SD) rats were randomly divided into sham-operated group (S group, n=7), I/R group (I group, n=35) and L-2THP treatment group (T group, n=35). Cerebral I/R model was reproduced in SD rats of I group and T group. HO-1 activity, cyclic GMP (cGMP) in the brain and COHb in blood were evaluated respectively at 1, 3, 12, 24, and 48 hours after global cerebral I/R and compared to those of the S group. Results: ① HOCD*21 activity, COHb content and cGMP level in I group increased as compared with those in S group after global cerebral I/R (all P

Expression of hemeoxygenase-1 and change of superoxide dismutase activity in perihematoma after intracerebral hemorrhage in rats / 临床神经病学杂志

Objective To study the expression of hemeoxygenase-1 (HO-1) and change of superoxide dismutase (SOD) activity in perihematoma after intracerebral hemorrhage (ICH). Methods The rats were randomly divided into sham operating group and intracerebral hemorrhage group.Rat ICH models were induced using stereotactic infusion autologous blood 50 ?l into the caudate nucleus. At the due time, the rats were killed and brain tissues were removed for detection of HO-1 and measurement of SOD by immunohistochemical and xanthine hydrocarbonylation methods. Results Following ICH, few HO-1 positive cells were observed in brain tissue perihemota at 6 h, peaked at 48 h ( P0.05), then decreased gradually and reached the minimum at 72 h ( P0.05). The change of SOD in brain tissue perihematoma was negatively correlated with the expression of HO-1 (r=-0.878, P

Rivalry mechanism of ginkgo in rat brain edema after intracerebral hemorrhage / 西安交通大学学报(医学版)

Objective To investigate the rivalry mechanism of ginkgo in rat brain edema after intracerebral hemorrhage.Methods Totally 80 healthy Wistar rats were divided into 4 groups randomly(20 rats in each group).Fifty microliters saline(group A and group B) or auto-hemoglobin(group C and group D) was infused into the right caudate nuclears using stereo tactic guidance.Groups A and C were lavaged 50 g/L carboxymethyl cellulose sodium solution of 3 mL,groups B and D were lavaged the same amount of ginkgo(200 mg/kg) solution dissolved by 50 g/L carboxymethyl cellulose sodium solution once a day for 3 weeks.All the rats were decapitated after raised for 3 weeks,and superoxide dismutase,malondialdehyde,and the number of hemeoxygenase-1(HO-1) positive cells in brains were assayed.Results The differences in SOD and MDA contents as well as HO-1 positive cell number between every two groups were significant(P