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Objective:To investigate the role of indoxyl sulfate (IS) in myocardial hypertrophy and fibrosis through organic anion transporter-3 (OAT-3) and oxidative stress in H9C2 cells.Methods:Rat myocardial cells (H9C2) were cultured and divided into four groups: Control group, IS group, siRNA negative control group (siOAT-3), and siOAT-3+ IS group. The control group was cultured routinely without IS stimulation. The IS group was stimulated with 250 μmol IS. The siRNA negative control group was transfected with 20 nmol/L OAT-3 siRNA, and the siOAT-3+ IS group was transfected with OAT-3 siRNA 48 hours later, then stimulated with IS for 24 hours. Real-time polymerase chain reaction (RT-PCR) was used to detect and analyze the mRNA expression levels of OAT-3, NADPH oxidase-4 (Nox-4), antioxidant proteins [nuclear factor E2 related factor 2 (Nrf-2), heme oxygenase 1 (HO-1)], myocardial hypertrophy markers [atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), β-myosin heavy chain gene (β-MHC)], and fibrosis markers [transforming growth factor β1 (TGF-β1), Smad homologous protein 3 (Smad-3), collagen type Ⅰ (Collagen Ⅰ)] in each group. H9C2 cells were further divided into three groups: Control group, IS group, and N-acetylcysteine (NAC) group. The NAC group was pre-treated with the antioxidant NAC before stimulation with 250 μmol IS for 24 hours. RT-PCR was used to detect the mRNA expression levels of the above indicators.Results:The mRNA expression level of OAT-3 in the IS group was significantly higher than that in the control group, while the mRNA expression levels of OAT-3 in the siOAT-3 group and the siOAT-3+ IS group were significantly lower than those in the IS group (all P<0.001). Compared with the Control group, the mRNA relative expression levels of Nox-4, ANP, BNP, β-MHC, TGF-β1, Smad-3, and Collagen Ⅰ in H9C2 cells of the IS group were significantly increased (all P<0.001), while the mRNA expression levels of Nrf-2 and HO-1 were significantly decreased (all P<0.001). Compared with the IS group, the mRNA relative expression levels of Nox-4, ANP, BNP, β-MHC, TGF-β1, Smad-3, and Collagen Ⅰ in H9C2 cells of the siOAT-3 group and the siOAT-3+ IS group were significantly lower (all P<0.001), while the mRNA expression levels of Nrf-2 and HO-1 were significantly increased (all P<0.001). Pre-treatment with NAC significantly inhibited the high expression of Nox-4, ANP, BNP, β-MHC, TGF-β1, Smad-3, and Collagen Ⅰ mRNA induced by IS (all P<0.001), while significantly increasing the mRNA expression levels of Nrf-2 and HO-1 (all P<0.01). Conclusions:IS promotes myocardial hypertrophy and fibrotic factor overexpression in H9C2 cells through OAT-3 and oxidative stress.
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Objective:To investigate the changes of coagulation/fibrinolysis factors in patients with type A aortic dissection (AD) at early and middle stages after ascending aorta replacement+ total arch replacement+ elephant nose stenting.Methods:According to the inclusion and exclusion criteria, patients with type A AD who underwent cardiac surgery in Xinjiang Uygur Autonomous Region People′s Hospital from August 2017 to August 2018 were selected as the study group. According to the duration of onset, patients were divided into acute AD group (course <2 weeks) and chronic AD group (course ≥2 weeks). Both groups were treated with ascending aorta replacement + total arch replacement + elephant nose stenting. Fasting venous blood was drawn from the two groups, and the blood indexes [prothrombin time (PT), activated partial thrombo plastin time (APTT), fibrinogen (Fib), bone morphogenetic proteins (BMP)] and fibrinolysis indexes [D-dimer, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI)] were detected by enzyme-linked immunosorbent assay (ELISA).Results:The ELISA result showed that changes of PT, APTT, Fib, BMP, D-dimer, and PAI in patients with acute and chronic AD at 12 months after operation were significantly lower than those before operation ( P<0.05). The changes of t-PA in patients with acute and chronic AD at 12 months after operation were significantly higher than those before operation ( P<0.05). There was no significant difference in postoperative effective rate, in-hospital mortality, length of stay, incidence of complications and early and mid-term survival rate between the two groups ( P>0.05). Conclusions:Ascending aorta replacement+ total arch replacement+ elephant nose stent is effective in the treatment type A AD, and can significantly improve the expression of coagulation/ fibrinolysis markers in early and middle period after operation.
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Objective:To investigate the clinical effects, inflammatory stress and immune cell levels of patients with acute aortic dissection (AD) after thoracic aortic endovascular repair (TEVAR).Methods:A retrospective analysis of 60 patients with acute aortic dissection admitted to our hospital from April 2014 to January 2016 were divided into conservative group ( n=30) and TEVAR group ( n=30) according to different treatment methods. The conservative group was given drug therapy, and the TEVAR group was given a thoracic aortic endovascular repair therapy. The inflammatory cytokines and immune cell levels of the two groups were measured before and after treatment. The therapeutic effects and the long-term effects of the two groups were analyzed. Results:Before treatment, there was no significant difference in serum interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) levels between the two groups ( P>0.05). After treatment, the levels of inflammatory cytokines in the two groups were significantly lower than those before treatment ( P<0.05); The levels of IL-6, IL-8 and TNF-α in the TEVAR group were significantly lower than those in the conservative group ( P<0.05). Before treatment, there was no significant difference in white blood cell count, neutrophil count, lymphocyte count and monocyte count between the two groups ( P>0.05). After treatment, the number of white blood cells and neutrophils decreased significantly in the two groups; and the number of lymphocytes in the two groups was significantly increased ( P<0.05). The number of white blood cells and neutrophils in the TEVAR group was significantly lower than that in the control group, and the number of lymphocytes was significantly higher than that in the conservative group ( P<0.05). The effective rate of the TEVAR group was significantly higher than that of the conservative group ( P<0.05). There was no significant difference in hospital mortality, hospitalization time and hospitalization complication between the two groups ( P>0.05). The 2-year survival rate of the TEVAR group was significantly higher than that of the conservative group. The postoperative complication rate was significantly lower than the conservative group ( P<0.05). There was no significant difference in the 1-year survival rate and secondary intervention rate between the two groups ( P>0.05). Conclusions:TEVAR has a better therapeutic effect, and improve survival rate to some extent.
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Objective To investigate stress induced Nox-4 expression and to explore its role in adipose inflammation. Methods Twenty male Kunming mice were randomly divided into two groups ( n=10 each) , chronic restraint stress group and control group. Stress mice were restrained in self-made restraint device for 2 hours per day for 14 days. HE staining, immunohistochemistry, RT-PCR, and ELISA were used to analyze the expression of Nox-4, CD11b, antioxidant protein ( Mn SOD, GSH-Px, Catalase), adipocytokines ( adiponectin, MCP-1, IL-6, TNF-a). Results White adipose tissue (WAT) of stress mice inguinal fat pad significantly shrank compared to control group. HE staining showed that there were a large number of mononuclear cells, neutrophils, eosinophils, and cell infiltration reactions and inflammatory changes in WAT of stress mice. The stress significantly increased CD11b-positive cells and the expression of mF4/80, CD68. The concentration of serum FFA in stress group increased significantly, nearly twice of the control group ( P<0.01) . Nox-4 positive staining cells in stress WAT were deeper and more abundant. The level of Nox-4 in stress WAT was significantly higher than that of control group(P<0.01). The levels of antioxidant proteins such as Mn-SOD, GSH-Px, and catalase in stress WAT were significantly lower than those of control group (P<0.01). The expression levels of adiponectin in stress WAT were significantly reduced as compared to control group ( P<0.01) . The levels of MCP-1, IL-6 and TNF-α in stress WAT were significantly higher than those in control group (P<0.01). Conclusion Stress may lead to imbalance of adipose oxidation/antioxidant system and abnormal expression of adipocytokines, which may result in adipose inflammation.
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Objective To investigate preoperative myocardial enzymes and realative influencing factors in Stanford B type aortic dissection.Methods From Jan.2004 to Sep.2013,151 consecutive patients with Stanford type B aortic dissection were admitted to hospital,aged from 31 to 76 average:(51.51 ± 10.90)year sold.Ninty-five healthy people with similar age and sex were taken as the control group.Fasting venous blood collected more than 12h was collected,myocardial enzymes indexes such as CK,CKMB,LDH,HBDH were measured by Roche modular automatic biochemical analysis system.Primary entry tear and extent of aortic dissection was measured by Toshiba Aquilion ONE 320 slice CT.Degree of aortic valve insufficiency was measured by Philips Sonos 5500 Color Doppler ultrasonic diagnostic apparatus.Results Compared with control group,the level of myocardial enzymes (LDH,HBDH) of aortic dissection group increased significantly(P < 0.01).part myocardial enzymes indexes(CK,LDH,HBDH) of acute stage group existed difference(P < 0.05).Myocardial enzymes indexes only CK existed difference between acute stage group and subacute stage group and chronic stage group(F =18.72,P =0.000),no difference between subacute stage group and chronic stage group.LDH,HBDH of each sub group of aortic dissection group were higher than that of control group,P < 0.01.Trough correlation analysis,CK negatively correlated with disease course of aortic dissection and patients sex [(r =-0.446 ; P =0.000) ; (r =-0.303 ; P =0.000)],CKMB negatively correlated patients sex [(r=-0.203;P=0.020)],LDH negatively correlated with patients sex [(r =-0.171 ;P =0.049)],positively with left ventricular end-diastolic diameter and left ventricular end-systolic diameter [(r =0.202 ; P =0.022) ; (r =0.271 ; P =0.002)].HBDH positively correlated with left ventricular enddiastolic diameter and left ventricular end-systolic diameter [(r =0.385 ;P =0.002) ; (r =0.515 ; P =0.000)],negatively with degree of aortic insufficiency [(r =-0.528 ;P =0.006)].Conclusions Myocardial enzymes rise in preoperative Stanford B aortic dissection,more representing skeletal muscle injury.Be affected by stage of aortic dissection,lower limb skeletal muscle injury aggravates more seriously in acute stage group persists entering the sub acute stage.