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Aim To investigate the mechanism of high salt-induced cerebral artery remodeling in mice by up-regulating TMEM16A. Methods Forty C57BL/6J mice were randomly divided into four groups (10 per group, 8 weeks of intervention), namely, blank control group (normal diet), low-salt group (2% high salt diet), medium-salt group (4% high salt diet) and high-salt group (8% high salt diet). HE staining was used to observe the morphological changes of cerebral arteries; blood vessel permeability test was used to compare the color and absorbance value of brain tissue. Immunofluorescence was employed to detect TMEM16A expression in cerebral arteries of mice in each group; PCR and Western blot were applied to detect the mRNA and protein expression of TMEM16A in cerebral arterial tissues; whole-cell patch clamp was use to record the calcium-activated chloride channel (CaCC) currents of mouse cerebral artery smooth muscle cells in each group. Results HE results showed that 2%, 4%, and 8% high salt diet could concentra-tion-dependently induce cerebral arterial wall thickening and lumen stenosis in C57BL/6J mice. The permeability test found that compared with the control group, the absorbance value of the brain tissue of the mice in the 2%, 4% and 8% high salt groups increased significantly. The results of isolated muscle tension showed that compared with the control group, the systolic response of isolated cerebral arteries to 60 mmol • L
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OBJECTIVE@#To investigate whether Shenfu Injection (SFI, ) can alleviate post-resuscitation myocardial dysfunction by inhibiting the inflammatory response.@*METHODS@#After 8 min of ventricular fibrillation and 2 min of basic life support, 24 pigs were randomly divided into 3 groups (n=8), which were given intravenous bolus injections of SFI (1.0 mL/kg), epinephrine (EP, 0.02 mg/kg) and normal saline (SA), respectively. The animals were sacrificed at 24 h after restoration of spontaneous circulation (ROSC), and serum interleuking-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) mRNAs and proteins were determined by RT-PCR and Western blot, respectively.@*RESULTS@#Compared with the EP and the SA groups, the ultrastructure of myocardial cells were slightly damaged and the systolic function of the left ventricle was markedly improved in the SFI group at 24 h after ROSC (P<0.05). In addition, compared with the EP and SA groups, the SFI group also showed significantly reduced levels of serum IL-6 and TNF-α, protein and mRNA levels of myocardial NF- κB and TLR4 (P<0.05).@*CONCLUSIONS@#Activation of TLR4/NF-κB signaling pathway may be involved in the pathological mechanisms of post-resuscitation myocardial dysfunction. SFI may block NF-κB-mediated inflammatory response by reducing the activity of NF- κB and the level of TNF-α, thus playing a protective role in post-resuscitation myocardial dysfunction.
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Objective Lipid metabolism disorders caused by cell foam plays an important role in atherosclerosis,but wheth-er it is involved in the development and progression of silicosis has not yet been elucidated. This study aimed to investigate the effect of free silica(SiO2) in inducing foam cell formation of NR8383 alveolar macrophages in rats. Methods NR8383 cells were cultured in vitro by the routine method (the control group) or in 50 μg/mL SiO2 (the SiO2group), 50 μg/mL ox-LDL (the ox-LDL group), or 50 μg/ml SiO2and ox-LDL (the model group), all for 36 hours. The survival rate of the cells was calculated with the cell proliferation and cytotoxicity assay (MTS),the lipid deposition observed by oil red O staining,the levels of total cholesterol (TC), free cholesterol (FC) and cholesterol esters(CE) measured by ELISA,and the mRNA and protein expressions of PPARγ and CD36 in the cells determined by RT-PCR and Western blot, respectively. Results Compared with the control group,the cells treated with ox-LDL showed a significantly increased survival rate, which reached the peak at 50 μg/mL ([1.501±0.201]%) (P<0.05). Foam cells were observed in the SiO2,ox-LDL and model groups,but most significantly in the model group. In comparison with the ox-LDL group,the model group exhibited remarkable increases in TC([14.195±2.260] vs[35.764±4. 226] μg/mg,P<0.05),FC([7.722±0.690] vs[10.049±0.698] μg/mg,P<0.05),CE([6.473±1.707] vs[25.715±4.243] μg/mg,P<0.05),and CE/TC (45.057% vs 71.642%, P<0.05). Conclusion Free SiO2promotes the lipid metabolism disorder in macrophages and enhances the foaming of the cells,in which PPARγ and CD36 may play an important role of regulation.
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Aim To study the role of Cx43 in inhibi-tion of AngII-induced vascular smooth muscle cells(VSMCs) proliferation by farrerol. Methods The primary VSMCs were isolated and cultured by direct adherent culture methods. VSMCs were identified by immunohistochemstry. The cells were divided into the following groups:control group,AngII group,AngII+Farrerol group. The cell viability was measured by CCK-8 cell vitality test. The proliferation of VSMCs was measured by the methods of Edu. The cell cycle of VSMCs was detected by flow cytometry. The mRNA levels of Cx43 were measured by Real-time PCR. The protein levels of Cx43 were measured by Western blot. Results 60 μmol·L-1farrerol could significantly de-crease the cell viability and EdU rate of VSMCs in-duced by AngII(P<0.05),which could also prevent the transformation of VSMCs from G0/G1phase to S phase. The results of real-time PCR and Western blot showed that,compared with the model group,Farrerol could significantly reduce the mRNA and protein ex-pression level of Cx43(P <0.01). After the interfer-ence of Cx43 by siRNA, the inhibition of proliferation by farrerol decreased significantly. Conclusion Far-rerol inhibits AngII-induced VSMCs proliferation signif-icantly, which might be associated with reducing the expression of Cx43.
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To investigate the diastolic function of quercetin on rat renal artery in vitro and its mechanism, the tension of rat renal artery was recorded by multi myograph system, and the L-type voltage-gated Ca channels (LVGC) current was recorded by whole-cell patch clamp technique. Quercetin produced relaxation effect on rat renal artery pre-contracted by 60 mmol/L KCl or 1 × 10 mol/L phenylephrine, and the maximal diastolic percentage was (84.53 ± 7.35)% or (76.42 ± 4.63)%. There was no statistical difference in the maximal diastolic percentage between endothelium-intact and endothelium-denuded groups. Pre-incubation of protein kinase C (PKC) inhibitor C6303 inhibited the maximal diastolic amplitude induced by quercetin. The peak current density of LVGC in rat renal artery vascular smooth muscle cells (VSMCs) was (23.17 ± 1.33) pA/pF. Quercetin (10 μmol/L) inhibited the peak current to (10.46 ± 1.35) pA/pF, and the inhibition percentage was 54.86%. C6303 (1 μmol/L) partially reversed the inhibitory effect of quercetin, and the inhibition percentage was 62.08% (P < 0.05). These results suggest that quercetin can relax rat renal artery in vitro in a concentration-dependent and endothelium-independent manner. The vasodilation of quercetin may be related to inhibition of LVGC current and activation of PKC.
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In order to explore the mechanisms underlying the vasoconstriction induced by blockade of inward rectifier Kchannels (K) with BaCl, myogenic tone of isolated rat coronary artery (RCA) was recorded with wire myograph. The dependence of BaCl- induced contraction on intracellular Ca([Ca]) release and extracellular Ca([Ca]) influx was studied by Cadeprivation and restoration. The mechanisms underlying BaCl-induced RCA contraction were investigated with specific inhibitors. BaCl(0.1-1.0 mmol/L) contracted isolated RCA in a concentration-dependent manner and the maximal contraction was (5.69 ± 1.07) mN, nearly equal to contraction induced by 60 mmol/L KCl. The contractions induced by BaClin Ca-free solution and by followed restoration of 2.5 mmol/L Caaccounted for (35.44 ± 6.72)% and (64.56 ± 5.94)%, respectively. Calcium channel blocker nifedipine (0.3 μmol/L), cyclooxygenase inhibitor indomethacin (100 μmol/L), ERK1/2 inhibitor PD98059 (10 μmol/L) and chloride channel blocker niflumic acid (100 μmol/L) pretreatment depressed the BaCl-induced maximal contraction by (87.82 ± 5.43)% (P < 0.01), (73.23 ± 5.47)% (P < 0.01), (75.69 ± 7.94)% (P < 0.01) and (83.24 ± 7.69)% (P < 0.01), respectively. These results demonstrate that BaClinduces vasoconstriction in RCA by enhancing both [Ca]release and [Ca]influx, and suggest that increase of prostanoids synthesis, activation of calcium channels and chloride channels, as well as ERK1/2 pathway may be involved in this process.
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<p><b>OBJECTIVE</b>To compare the effects of Shenfu Injection (SFI) and epinephrine (EPI) on catecholamine levels in a porcine model of prolonged cardiac arrest (CA).</p><p><b>METHODS</b>After 8 min of untreated ventricular fibrillation, 24 Wuzhishan miniature pigs were randomly assigned to one of the three groups (n=8 per group) and received central venous injection, respectively: SFI group (1 mL/kg), EPI group (20 μg/kg EPI), and normal saline (NS) group. Cardiac output (CO), maximum rate of increase/decrease in left ventricular pressure (±dp/dt), serum levels of EPI, norepinephrine (NE), and dopamine (DA) were determined at baseline and at 0.5, 1, 2, and 4 h after restoration of spontaneous circulation.</p><p><b>RESULTS</b>The duration of cardiopulmonary resuscitation was shorter in the EPI and SFI groups than in the NS group (P<0.05). The EPI level increased significantly after restoration of spontaneous circulation (ROSC) in all three groups, and was significantly different between the EPI group and the other two groups immediately after ROSC (both P<0.01), but these differences gradually disappeared over time. There were no significant differences in NE or DA levels among the three groups, and there were no correlations between catecholamine levels and CO or dp/dt (P>0.05).</p><p><b>CONCLUSIONS</b>SFI did not significantly affect endogenous catecholamine levels during cardiopulmonary resuscitation after prolonged ventricular fibrillation. However, SFI improved oxygen metabolism, and produced a better hemodynamic status compared with EPI. SFI might be a potentially vasopressor drug for the treatment of CA.</p>
الموضوعات
Animals , Cardiac Output , Cardiopulmonary Resuscitation , Catecholamines , Blood , Disease Models, Animal , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Epinephrine , Pharmacology , Therapeutic Uses , Heart Arrest , Blood , Drug Therapy , Heart Ventricles , Injections , Lactic Acid , Blood , Sus scrofaالملخص
<p><b>OBJECTIVE</b>To observe the effect of parecoxib on morphine dosage in patient-controlled analgesia (PCA) following thoracoscope-assisted thoracotomy.</p><p><b>METHODS</b>A consecutive series of 100 patients undergoing thoracoscope-assisted thoracotomy were randomized into 5 groups and received PCA with morphine doses at 0, 5, 10, 15, and 20 mg given in 200 ml saline (groups P(1), P(2), P(3), P(4), and P(5), respectively). Parecoxib (40 mg) was given in all the patients immediately before the operation, and the mixture (4-5 ml) of lidocaine and ropivacaine was administered into the 3 intercostal spaces upper and lower to the incision before chest closure. PCA was administered for each patient. The visual analogue scale (VAS) at rest and coughing and the respiratory functional parameters were recorded at 1, 2, 4, 8, 12, 24, 36, and 48 h after the start of PCA, and the actual and effective button-pressing times (D(1)/D(2)) in PCA were also recorded.</p><p><b>RESULTS</b>No patients showed signs of respiratory inhibition within 24 h after the operation, and the resting VAS was comparable between the groups within the initial 6 postoperative hours. At 8 to 24 h postoperatively, the VAS scores at rest and coughing were significantly higher in P(1) group than in the other groups (P<0.05), and no significant differences were found between the groups at 36 to 48 h. D(1)/D(2) in groups P(1) and P(2) were significantly different from those in the other 3 groups at 4-24 h, but no such difference was found between groups P(3), P(4), and P(5).</p><p><b>CONCLUSION</b>The application of parecoxib may reduce the dosage of morphine in PCA following thoracoscope-assisted thoracotomy and results in good analgesic effect without affecting the patients respiratory function and sputum elimination.</p>
الموضوعات
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Analgesia, Patient-Controlled , Methods , Combined Modality Therapy , Double-Blind Method , Isoxazoles , Morphine , Pain, Postoperative , Drug Therapy , Thoracoscopy , Thoracotomy , Methodsالملخص
@#ObjectiveTo evaluate the effect of rehabilitation nursing in the peri-operative period of the first-stage combined anterior-posterior approach surgery in the sacral tumor resection.Methods15 patients with sacral tumor received psychological intervention, gastrointestinal preparation, exercises of perineum sphincter contraction and relaxation training before the operation. Changes of patients' vital signs and nerve function were observed after the operation, and rehabilitation training and instruction were performed.ResultsAll cases were followed up for 2~37 months. Except one case died of tumor transfered to lung, all of other cases had a satisfactory curative effect in the near future, and their local symptom released and the functions of urination and defecation were kept well.ConclusionRehabilitation nursing in the peri-operative period plays an important role in surgical treatment of sacral tumor. It affects the rehabilitation and function restitution obviously and can reduce the occurrence of complication effectively.