Effect of surgery under propofol anesthesia during mid-pregnancy on cognitive function and hippocampal HDAC2-CREB-NR2B signaling pathway in offspring rats / 中华麻醉学杂志

Objective:To evaluate the effect of surgery under propofol anesthesia during mid-pregnancy on the cognitive function and hippocampal histone deacetylase 2 (HDAC2)-cAMP response element-binding protein (CREB)-N-methyl-D-aspartate (NMDA) receptor 2B subunit (NR2B)-containing NMDA receptor (NR2B) signaling pathway in the offspring rats.Methods:Thirty healthy Sprague-Dawley rats at 14 days of gestation were divided into 3 groups ( n=10 each) using a random number table method: propofol anesthesia group (P group), surgery under propofol anesthesia group (S group) and control group (C group). In S group, propofol 20 mg/kg was injected via the caudal vein, and then propofol was continuously infused at a rate of 20 mg·kg -1·h -1 to maintain anesthesia for 4 h, and exploratory laparotomy was performed. Group P received no exploratory laparotomy and the other treatments were similar to those previously described in group S. The equal volume of normal saline was given instead in group C. The learning and memory of the offspring rats was assessed using Morris water maze test on postnatal day 30. The expression of HDAC2, phosphorylated CREB (p-CREB), NR2B, brain-derived neurotriphic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) in offspring′s hippocampi was evaluated by Western blot. Apoptosis in hippocampal neurons was detected by TUNEL staining. Results:Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in P and S groups ( P<0.05). Compared with P group, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in S group ( P<0.05). Conclusions:Surgery under propofol anesthesia during mid-pregnancy can decrease the cognitive function of offspring rats, and the mechanism is related to the regulation of HDAC2-CREB-NR2B signaling pathway and the promotion of apoptosis in hippocampal neurons.

The correlation of HDAC2 polymorphisms with alcohol use disorder in male people of Han nationality / 中华行为医学与脑科学杂志

Objective:To explore the association between polymorphism of Histone Deacetylase 2 (HDAC2) gene and alcohol use disorder (AUD) in male people of Han nationality for seeking suitable single nucleotide loci(SNP), and provide reference for early diagnosis and intervention of alcohol use disorder(AUD).Methods:A total of 194 male AUD patients of Han nationality (case group) and 310 normal men of Han nationality (control group) were selected for the study. The genomic DNA of peripheral blood of the subjects in the two groups was extracted, and 13 SNP loci of HDAC2 gene were obtained from HapMap database. The subjects in the two groups were genotyped by Agena MassARRAY SNP genotyping method.SPSS 25.0 was used to statistically analyze the differences of genotype frequency and allele frequency between the two groups, and Haploview 4.2 software was used for linkage disequilibrium and haploid analysis. The multiple test correction was carried out by the replacement test with 50 000 replacement times.Results:The genotype frequency of the 3 SNP loci(rs9481408, rs6568819, rs9488289) of HDAC2 gene were statistically significant different between the case group and the control group (all P<0.05). Further analysis found that the three loci were significantly correlated with AUD in the recessive genetic model between case group and control group(T/T vs C/C-C/T: OR=1.78, 95% CI: 1.05-3.03, P=0.033; T/T vs C/C-C/T: OR=1.79, 95% CI: 1.05-3.03, P=0.032; G/G vs C/C-C/G: OR=1.85, 95% CI: 1.09-3.13, P=0.022). Seven SNP haplotypes were constructed and the association odds ratio of GATCTGCAATAA between the case group and control group was 2.44, and the difference was statistically significant ( P<0.05). Conclusion:The SNP loci rs9481408, rs6568819, rs9488289 in the HDAC2 gene and haplotype GATCTGCCAATAA are associate with AUD in male people of Han nationality. These results indicated that the HDAC2 gene is one of the susceptibility genes of AUD.

Huatanjiangqi capsule regulates Nrf2/HDAC2 and improves glucocorticoid resistance of 16HBE cells / 中国临床药理学与治疗学

AIM: To explore the effect of Huatanjiangqi capsule medicated serum (HTJQ) on the resistance of human bronchial epithelial cells (16HBE) to glucocorticoid (GC) stimulated by cigarette smoke extract (CSE). METHODS: After 16HBE cells were treated with HTJQ, the effects of different concentrations of HTJQ on the viability of 16HBE cells were determined by CCK-8 method. 16HBE cells were pretreated with HTJQ, and then cultured with dexamethasone (DEX) and lipopolysaccharide (LPS) for 24 hours, the effect of HTJQ on glucocorticoid (GC) resistance of 16HBE cells was determined by Enzyme-linked immunosorbent assay (ELISA). The effects of HTJQ, sulforaphane (SFN) and glutathione (GSH) on the expression of NF-E2-related factors 2 (Nrf2), Heme oxygenase-1 (HO-1) and histone deacetylase 2 (HDAC2) in 16HBE cells stimulated by CSE were measured by Western blot, and the effects of HTJQ, SFN and GSH on interleukin-8 (IL-8) in 16HBE cells were measured by ELISA. RESULTS: HTJQ promoted the proliferation of 16HBE cells at 1 h, 2 h and 4 h, the results of ELISA and Western blot showed that CSE induced GC resistance and decreased the expression of Nrf2, HO-1 and HDAC2 in 16HBE cells, HTJQ significantly decreased IL-8 and improved GC sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). In addition, HTJQ significantly up-regulated the level of GSH in 16HBE cells (P<0.01). Nrf2 agonists SFN and GSH significantly improved the glucocorticoid sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). CONCLUSION: HTJQ improves the GC resistance of 16HBE cells by up-regulating the expression of Nrf2/HDAC2 protein and the level of intracellular GSH.

MicroRNA144￣3p targeting histone deacetylase 2 promoting cardiomyocyte hypertrophy and cardiac function damage / 解剖学报

Objective To investigate the role and possible mechanism of microRNA(miR)144-3p in promoting cardiomyocyte hypertrophy. Methods Forty-five C57BL/ 6 mice were divided into control group, myocardial hypertrophy model group (model group), and miR144-3p transfection group (transfection group) according to their transfection method. The cardiac function related indexes of three groups of mice were detected. HE staining was performed on mouse myocardial tissue.The expression of miR144-3p in mouse cardiomyocytes was detected by Real-time PCR. Antinuclear factor (ANF), β-myosin heavy chain (β-MHC), actin α1 (Acta1) and histone deacetylase 2 (HDAC2) were detected by Western blotting in three groups. Results Compared with the control group, the interventricular septal thickness- diastolic(IVSd), interventricular septal thickness-systolic(IVSs), diastolic left ventricular posterior wall thickness(IVPWd), systolic left ventricular posterior wall thickness(IVPWs), ejection fraction(EF), cardiac weight index and left cardiac index of the model group and the transfection group were significantly higher, while systolic left ventricular diameter (LVDs) and diastolic left ventricular diameter(LVDd)were lower (P0. 05). Compared with the control group, the relative expression of miR144-3p in the model group and the transfection group was significantly higher than that in the model group (P<0. 05). Compared with the control group, the expression levels of antinuclear factor, β-myosin heavy chain, Actinα1 and histone deacetylase 2 in the model group and the transfected group were significantly higher (P<0. 05). Conclusion miR144-3p can aggravate cardiac hypertrophy by up-regulating HDAC2 and is expected to become a new therapeutic target.

Early intervention of bone-nearby acupuncture combined with electroacupuncture on morphine tolerance in bone cancer pain rats and its effect on the expression of HDAC and MOR in dorsal root ganglia / 中国针灸

OBJECTIVE@#To observe the effect of early intervention of bone-nearby acupuncture (BNA) combined with electroacupuncture (EA) on the expression of histone deacetylase1(HDAC1), histone deacetylase 2 (HDAC2) andμ-opioid recepter (MOR) in dorsal root ganglia (DRG) of bone cancer pain-morphine tolerance (BCP-MT) rats, and to explore its possible mechanism.@*METHODS@#A total of 35 SD rats were randomized into a sham BCP group (=6), a BCP group (=7), a MT group (=7), a BNA+EA group (=8) and a shame BNA group (=7). Except of the sham BCP group, cancer cell inoculation operation at left tibia was given in the other 4 groups to establish the bone cancer pain model. In the MT group, the BNA+EA group and the shame BNA group, intraperitoneal injection of morphine hydrochloride was given to establish the morphine tolerance model. After the operation, bone-nearby acupuncture combined with electroacupuncture was applied at "Zusanli" (ST 36) and "Kunlun" (BL 60) in the BNA+EA group, with dilatational wave, 2 Hz/100 Hz in frequency, 0.5 to 1.5 mA in intensity. Intervention in the shame BNA group was applied at the same time and acupoints as those in the BNA+EA group, the needles were pierced the skin without any electrical stimulation. The needles were retained for 30 min, once a day for continuous 7 days in both BNA+EA and shame BNA groups. Before and 10, 11, 15, 22 days after the operation, the left paw withdrawal threshold (PWT) was measured in the 5 groups. The levels of HDAC1, HDAC2 and MOR in DRG were detected by Western blot.@*RESULTS@#Ten days after the cancer cell inoculation operation, the PWT of the BCP, MT, BNA+EA and sham BNA groups was decreased compared with the sham BCP group (0.05); the PWT of the BNA+EA group was increased compared with the MT and sham BNA group (<0.01). In the BCP group, the DRG levels of HDAC1 and HDCA2 were increased, while the level of MOR was decreased compared with the sham BCP group (<0.05, <0.01). In the MT group, the DRG level of HDAC1 was increased compared with the BCP group (<0.05). In the BNA+EA group, the DRG level of HDAC1 was decreased compared with the MT group and the sham BNA group (<0.01, <0.05), while the level of MOR was increased (<0.01).@*CONCLUSION@#Early intervention of bone-nearby acupuncture combined with electroacupuncture can relieve the morphine tolerance in bone cancer pain rats, it may relate to down-regulating the expression of HDAC1 and up-regulating the expression of MOR in the dorsal root ganglia.

Mechanisms of electroacupuncture underlying treatment of osteoporosis based on HDAC2-mediated osteoblast differentiation pathway / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of histone deacetylase 2 (HDAC2), histone H3, bone formation related genes and proteins in osteoporosis rats, so as to reveal its mechanisms underlying improvement of osteoporosis. METHODS: Female SD rats were randomly divided into 4 groups: sham operation, model, EA and medication (n＝ 10 rats in each group). The osteoporosis model was established by castration. EA (2 Hz, 1 mA) was applied to bilateral "Shenshu" (BL23) and "Pishu" (BL20) for 10 min, once every other day for 8 weeks. Rats of the medication group received subcutaneous injection of 17 β-estradiol (100 µg/kg, 20 µg/mL). The bone quality and quantity including the cortical bone mineral density (CBMD), trabecular bone mineral density (TBMD), ratio of bone volume /total volume (BV /TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb. Sp), trabecular bone pattern factor (Tb.Pf), and structure model index (SMI) of the right thigh-bone were detected by using a micro-computed tomography. Serum alkaline phosphatase (ALP) and estrogen 2 (E2) contents were assayed by using colorimetry and ELISA, expression levels of HDAC2, histone H3 and Runx2 in the thigh-bone were detected using Western blot, and that of Runx2 mRNA was detected using quantitative real-time PCR, separately. The co-expression of Ac-histone H3/Runx2 and Runx2/ALP was observed by using immunofluorescence histochemical staining. RESULTS: After modeling, the levels of TBMD, BV/TV, Tb.Th, and Tb.N, serum E2 and ALP, and expression of Runx2 protein and mRNA, Ac-histone and ALP proteins were significantly lower (P0.05). The effects of EA were significantly superior to 17 β-estradiol in down-regulating the expression of HDAC2 and histone H3 proteins and in up-regulating expression of Ac-histone H3 protein (P<0.01，P<0.05)．. CONCLUSION: EA treatment can increase bone density, increase bone mass and trabecular bone, and promote trabecular bone rod-like changes in plate shape in osteoporosis rats, which is related to its effect in up-regulating the expression of Ac-histone H3 protein, and down-regulating the expression of bone formation-related proteins.

Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

Antioxidant mechanism of HDAC2 regulating Nrf2 acetylation in LPS-induced type Ⅱ alveolar epithelial cell injury / 中华急诊医学杂志

Objective To explore the antioxidant mechanism ofhistone deacetylase 2 (HDAC2) regulating Nrf 2 acetylation in lipopolysaccharide (LPS)-induced type Ⅱ alveolar epithelial cell injury.Methods The experiment was divided into two parts.The first part was the routine culture of type Ⅱ alveolar epithelial cells of mice.The cells were stimulated with different concentrations of LPS (10 ng/ mL,100 ng/mL and 1 000 ng/mL).CCK-8 was used to detect the cell activity at 0 h,6 h,12 h,24 h and 48 h,respectively.The second part:Alveolar epithelial cells of type Ⅱ were cultured and divided into the normal control group (control group),LPS group,HDAC2 lentivirus interference group (siRNA-HDAC2 group) and HDAC2 lentivirus overexpression group (LV-HDAC2 group).The expression of HDAC2 and Nrf2 were detected by Western blot,the acetylation of Nrf2 was detected by immunoprecipitation,and the stability of nrf2 was detected after actinidone action.The activity of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by chemical colorimetry.SPSS 23.0 statistical software was used.LSD-t test was used for comparison between two groups,and one-way ANOVA test was used for comparison among multiple groups.Results Compared with the control group,the expression of HDAC2 protein in the LPS group increased (t=5.974,P=0.027),the acetylation level of Nrf2 decreased (t=7.223,P=0.002),the Nrf2 protein level increased (t=2.929,P=0.043),the protein stability of Nrf2 increased,the SOD activity decreased (t=121,P＜0.01),and the MDA content increased (t=10.45,P=0.000 5).Compared with the LPS group,Nrf2 acetylation level decreased in the LV-HDAC2 group (t=1 1.29,P=0.000 4),Nrf2 protein expression increased (t=3.194,P=0.033),Nrf2 protein stability increased,SOD activity increased (t=4.678,P=0.009),and MDA content decreased in the LV-HDAC2 group (t=5.417,P=0.005 6).While the opposite trend was observed in the siRNA-HDAC2 group.Conclusion After LPS stimulation,oxidative stress of type Ⅱ alveolar epithelial cells was aggravated.HDAC2 could decrease the level of Nrf2 acetylation,increase the expression of Nrf2 protein,and alleviate LPS-induced oxidative stress.

The structure of histone deacetylase 2 and its role in diseases / 中国比较医学杂志

Histone acetylation is one of the most important reactions of post-translational modification of histones, which plays an important role in the regulation of epigenetic processes. Histone deacetylase 2 as a member of type I histone deacetylases,involved in the catalytic regulation of histone and a variety of non-histone deacetylation,regulates a variety of life processes. This paper summarizes the basic structure of histone deacetylase 2 and the role of histone deacetylase 2 in various diseases,and provides a theoretical basis for conducting related studies.

Propofol exposure in early pregnancy impairs learning and memory increases histone deacetylase in the offspring rats / 医学研究生学报

Objective Propofol exposure during pregnancy impairs learning and memory of the offspring rats, but its definite mechanisms are not yet clear.This study is to assess the impact of propofol exposure during early pregnancy on the learning, memory, and the expression of histone deacetylase 2 (HDAC2) in the hippocampus of the offspring rats.Methods Twenty Sprague-Dawley rats at gestation days 5-7, weighing 270-320 g, were equally randomized into a propofol exposure and a saline control group.The offspring rats of the former group were again divided into a propofol SAHA (n=50) and a propofol DMSO group (n=47), and those of the latter into a control SAHA (n=48) and a control DMSO group (n=45).On postnatal day 30, the offspring rats were subjected to the Morris water maze (MWM) test at 2 hours after intraperitoneally injected with the HDAC inhibitor subcroylanilide hydroxamic acid (SAHA) at 90 mg/kg and equal volume of dimethyl sulfoxide (DMSO), respectively.Then all the animals were sacrificed and the hippocampal tissue harvested for determination of the expression of the HDAC2 protein by immunofluorescence staining.Results On the 5th and 6th days of the MWM test, the escape latency was significantly prolonged in the propofol DMSO group ([65.93±30.42] and [50.72±24.72] s) as compared with the control DMSO ([29.32±16.38] and [21.34±13.79] s) and the propofol SAHA group ([42.52±20.43] and [24.28±13.41] s) (P<0.05), while the platform-crossing frequency was markedly lower in the former than in the latter two groups (P<0.05).The expression of the HDAC2 protein remarkalby up-regulated in the propofol DMSO group (1.37±0.03) in comparison with the control DMSO (1.00±0.02) and the control SAHA group (0.99±0.03) (P<0.05).Conclusion Propofol exposure in early pregnancy impairs learning and memory of the offspring rats, which is associated with the up-regulated expression of the HDAC2 protein in the hippocampus.

Effect of clarithromycin on expressions of HDAC2and GR in smoke-exposed asthmatic mice / 西安交通大学学报(医学版)

Objective To explore the effects of clarithromycin on the expressions of histone deacetylase-2 (HDAC2) and glucocorticoid receptor (GR) of cigarette smoke-exposed asthmatic mice.Methods BALB/c mice were chosen to be the subjects of this study.They were raised to establish asthma model (OVA group);and mice in one asthma group were exposed to smoke (SEA group), one asthma group were treated with clarithromycin (CAM group) after smoke exposure.Control group mice were used as parallel comparison.The histopathological changes were studied to assess lung tissue inflammation.Cell counts in bronchoalveolar lavage fluid were also tested for airway inflammation.Histone deacelytase2 (HDAC2) activity of lung tissues was measured by qRT-PCR.HDAC2 and GR expressions in the lung tissue were detected by Western blot.Results Histopathologic observation showed massive infiltration of inflammatory cells in both OVA group and SEA group, while inflammation infiltration attenuated in CAM group.Compared with those in CAM group, the levels of IL-4 and IL-8 in bronchoalveolar lavage fluid of SEA group increased significantly (104.36±14.39 vs.65.49±10.82, 681.35±66.18 vs.321.49±90.37;P=0.031, 0.017).The expression of HDAC2 mRNA in CAM group was significantly higher than that in SEA group (0.062±0.013 vs.0.031±0.015, P=0.032).The expressions of HDAC2 protein (0.23±0.017 vs.0.49±0.022, P=0.033) and GR protein (0.19±0.014 vs.0.64±0.023, P=0.011) were significantly lower in SEA group than in CAM group.Conclusion Clarithromycin could attenuate airway inflammation in smoke-exposed asthmatic mice.The mechanism of action may be related to the expression of HDAC2 gene in the lower reaches by combining with GR.

MicroRNA-455 suppresses the oncogenic function of HDAC2 in human colorectal cancer

Colorectal cancer (CRC) is the fourth leading cause of cancer-induced mortality. Histone deacetylase 2 (HDAC2) is involved in prognosis and therapy of CRC. This study aimed to explore novel therapeutic targets for CRC. The alteration of HDAC2 expression in CRC tissues was estimated by qRT-PCR. After lentivirus transfection, HDAC2 knockdown was confirmed by western blot analysis. The effect of HDAC2 knockdown on cell proliferation was then assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Screened by TargetScan, microRNA (miR)-455 was predicted to bind to 3′UTR of HDAC2 and the prediction was verified by luciferase assay. Finally, cells were transfected, respectively, with miR-455 mimics or miR-455 negative control (miR-NC) and the expression of HDAC2, cell proliferation and apoptosis of transfected cells were respectively evaluated by western blot analysis, MTT assay and flow cytometry. Results showed that the HDAC2 expression was up-regulated in CRC tissues (P<0.05). HDAC2 knockdown significantly decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after infection. Then, miR-455 was verified to directly target HDAC2, resulting in a significant difference in luciferase activity (P<0.01). Moreover, miR-455 decreased the expression of HDAC2 (P<0.01). miR-455 remarkably decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after transfection while inducing cell apoptosis (P<0.001). In conclusion, miR-455 inhibited cell proliferation while inducing cell apoptosis by targeting HDAC2 in CRC cells.

The implication of HDAC2 in diagnosis and treatment patients with acute exacerbation of chronic obstructive pulmonary disease / 预防医学

Objective To explore the correlation among the concentration of peripheral blood histone deacetylase 2 (HDAC2),C -reactive protein (CRP),proealeitonin (PCT)and lung function among patients with acute exacerbation period of chronic obstructive pulmonary disease (AECOPD).Methods A total of 60 patients with AECOPD were selected as the test group,and 40 healthy subjects in the same medical examination center were selected as the control group.The HDAC2,CRP,PCT,lung function testing and blood gas analysis were measured on Day 0,3,7,1 0.Results Along with the process of AECOPD patients,in the treatment of 0 d,3 d,7 d,1 0 d,the average level of CRP and PCT in peripheral blood of patients was decreased gradually,while the average level of HDAC2 was gradually increased (P<0. 05 ).In patients treated with 0 d,3 d,7 d,1 0 d,HDAC2 levels were negatively correlated with CRP and PCT at the same time (rCRP was-0. 31 6,-0. 435,-0. 495,-0. 547,respectively,and rPCT was -0. 41 4,-0. 332,-0. 481 ,-0. 523,respectively, P<0. 01 ).The level of HDAC2 was positively correlated with lung function in the same period (rFEV1 was 0. 594,and rFEV1/Expected value was 0. 561 ,P<0. 01 ).Conclusion HDAC2 may be a negative regulator of the inflammatory response among the patients with AECOPD,and is associated with the degree of airflow obstruction of the patients.

Effects of Shenqi Bufei Tang Decoction on the Expression of HDAC2 and NF-κB p65 in Airway Smooth Muscle Tissues of COPD Rats with Lung-Qi Deficiency Syndrome / 医药导报

Objective To examine the effects of Shenqi Bufei Tang decoction on the expression of histone deacetylase-2 ( HDAC2) and nuclear factor-κB p65 ( NF-κB p65) in the airway smooth muscle tissues of COPD rats with lung-qi deficiency syndrome. Methods A total of 40 male rats were randomly divided into normal control group,model control group,Shenqi Bufei Tang decoction group,and aminophylline group.The COPD rat model with lung-qi deficiency syndrome was established by intra-tracheal instillation of lipopolysaccharide (LPS) and passive smoking for 28 days.Pathological changes of lung tissues were ob-served under the light microscope and the thickness of the small airway wall and airway smooth muscle ( ASM) layer analyzed by the image analysis.Immunohistochemistry,real-time PCR and Western blotting were used to detect the expressions of NF-κB p65 and HDAC2 in ASM. Results The thickness of the airway wall and ASM,and the expression levels of NF-κB p65 mRNA and protein were significantly increased in the model control group when compared with those in the normal control group ( P0.05). Conclu-sion Shenqi Bufei Tang decoction can inhibit the proliferation of ASM in COPD rats with lung-qi deficiency syndrome,which may be associated with the increased expression of HDAC2 and decreased expression of NF-κB p65.

Treatment with 1,25(OH)2D3 induced HDAC2 expression and reduced NF-κB p65 expression in a rat model of OVA-induced asthma

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3 might be useful as a novel HDAC2 activator in the treatment of asthma.

Effect of cigarette smoking condensate on HDAC2 and inflammatory me-diators in mouse myoblast C2 C12 cells / 中国病理生理杂志

AIM:To investigate the effect of cigarette smoking condensate on histone deacetylase 2 (HDAC2) and inflammatory mediators in mouse myoblast C 2C12 cells.METHODS:C2C12 cells were treated with cigarette smoke extract (CSE).HDAC2 siRNA was transfected into the cells using Lipofectamine TM 2000.The levels of interleukin-8 (IL-8) and tumor necrosis factor-α( TNF-α) in the culture supernatants were measured by ELISA , and the expression of HDAC2 at mRNA and protein levels was determined by real-time PCR and Western blotting .RESULTS:The expression of HDAC2 at mRNA and protein levels in CSE group was lower than that in control group (P<0.05).The supernatant levels of IL-8 and TNF-αin CSE group were significantly higher than those in control group ( P<0.05 ) .When the cells were transfected with HDAC2 siRNA followed by CSE stimulation , the expression of HDAC2 at mRNA and protein levels was de-creased , and the supernatant levels of IL-8 and TNF-αwere significantly increased as compared with CSE group and control group (P<0.05).CONCLUSION: Under the oxidative stress condition , C2C12 cells generate high levels of IL-8 and TNF-αby down-regulating the expression of HDAC2.

Cigarette smoke extract promotes senescence by reducing expression of HDAC2 in C2C12 myoblasts / 中国病理生理杂志

AIM:To investigate whether the cigarette smoke extract (CSE) causes senescence of C2C12 myo-blasts and the relationship between senescence and histone deacetylase 2(HDAC2).METHODS: Murine C2C12 cells were induced to differentiate into myoblasts.The HDAC2 activator and inhibitor were used to investigate the effects of CSE in the myoblasts on cell senescence and the expression of HDAC2.The expression of HDAC2 at mRNA and protein levels was determined by real-time PCR and Western blot, respectively, and the positive cell rate of β-galactosidase staining for cell senescence was also detected.RESULTS:The optimal concentration of CSE was 60 mL/L and the intervention time was 24 h.After the intervention of CSE, the positive cell rate ofβ-galactosidase staining was increased, accompanied with the reduction of HDAC2 expression at mRNA and protein levels.The expression of HDAC2 at mRNA and protein levels was increased by 4, 5, 6, 7-tetrabromobenzotriazole (TBB), accompanied with the reduction of positive cell rate ofβ-galacto-sidase staining.Furthermore, when HDAC2 expression at mRNA and protein levels was reduced by HDAC2 inhibitor valp-roic acid, the positive cell rate of β-galactosidase staining was increased.CONCLUSION: CSE promotes the senescence by reducing the expression of HDAC2 in C2C12 myoblasts.