Objective To observe the expression changes of 5-hydroxytryptamine (5-HT),brainderived neurotrophic factor (BDNF) in rats with chronic manganism.Methods Sixty healthy male Sprague-Dawley rats were randomly divided into control group (n =15) and experimental group (n =45).The experimental group was divided into three subgroups:low-dose group (n =15),middle-dose group (n =15),high-dose group (n =15).The rats in control group were given intraperitoneal injection of normal saline while the rats in low-dose group,middle-dose group,high-dose group were given intraperitoneal injection of 5 mg/kg,15 mg/kg and 25 mg/kg manganese chloride tetrahydrate,respectively for 5 days oncea week and lasted for 12 weeks.The depressive behavior changes of rats were observed by sucrose preference test and open field test.The concentrations of manganese in the striatum of rats were detected by inductively coupled plasma-atomic emission spectrometry.The expression of 5-HT in frontal cortex,hippocampus of rats was determined by high performance liquid chromatography.The expression of BDNF in frontal cortex,hippocampus of rats was examined by Western blotting.The expression of BDNF mRNA was detected using real-time fluorescence quantitative polymerase chain reaction.Results The chronic manganese poisoning rats presented depression-like behavior based on the sucrose preference test and open field test,which was more distinct in high-dose rats.As compared with the control group (frontal cortex (459.65 ± 16.81) ng/g,hippocampus (323.92 ± 17.41) ng/g;tissue wet weight),the expressions of 5-HT were significantly decreased in frontal cortex ((423.45 ± 17.19) ng/g,(376.89 ± 18.87) ng/g,(280.17 ± 25.46) ng/g),hippocampus ((265.71 ± 17.89) ng/g,(214.35 ±23.63) ng/g,(172.67 ± 18.24) ng/g) of the experimental group (F =132.68,69.66,both P ＜ 0.05).As compared with the control group (frontal cortex 0.962 ±0.111,hippocampus 0.873 ± 0.101;the expressions of BDNF were significantly decreased in frontal cortex (0.855 ± 0.106,0.649 ± 0.112,0.506 ± 0.121) and hippocampus (0.731 ± 0.092,0.626 ±0.104,0.544 ± 0.113) with the increasing concentration of MnCl2 which showed dose dependence (F =13.26,18.54,both P ＜ 0.05).As compared with the control group (frontal cortex 0.000 87 ± 0.000 07,hippocampus 0.000 82 ± 0.000 09),the expressions of BDNF mRNA were decreased significantly in frontal cortex (0.000 71 ± 0.000 06,0.000 48 ± 0.000 03,0.000 36 ± 0.000 03) and hippocampus (0.000 57 ± 0.000 05,0.000 49 ± 0.000 04,0.000 38 ± 0.000 05) in the treated group with the increasing concentration of manganese (F =18.46,12.76,both P ＜ 0.05).Conclusion Rats with chronic manganese poisoning could present depression-like behavior and the expression of 5-HT and BDNF is decreased in the frontal cortex and hippocampus with the increased accumulation of manganese.

OBJECTIVETo study the changes in the expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FP1) in the substantia nigra (SN) of rats with manganese-induced parkinsonism.

METHODSEighty Sprague-Dawley rats were randomly divided into four groups. Rats in the control group were injected intraperitoneally with saline solution. Rats in the low-dose, medium-dose, and high-dose groups were injected intraperitoneally with 5, 15, and 20 mg/kg MnC12 solution, respectively, for 16 weeks. Three behavioral tests were performed at the 16th week. The concentration of Mn2+ in the SN was determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES), and the positive expression of tyrosine hydroxylase (TH) was measured by immunohistochemical staining to determine whether rats with manganese-induced parkinsonism were successfully produced. The expression of DMT1 and FP1 in SN was measured by immunohistochemical staining and fluorescent quantitative polymerase chain reaction.

RESULTSRats with manganese-induced parkinsonism were successfully produced using the above method. Compared with that in the control group, the concentrations of Mn2+ in the SN of rats exposed to 5, 15, and 20 mg/kg Mn2+ were significantly higher (1.72?0.33 vs 0.56 ± 0.20 µg/g, P<0.01; 2.92±0.77 vs 0.56±0.20 µg/g, P<0.01; 5.65±1.60 vs 0.56±0.20 µg/g, P<0.01). The mean ODs of TH-positive cells in the SN of rats exposed to 5, 15, and 20 mg/kg Mn+ were significantly lower than that in the control group (0.054±0.008 vs 0.109±0.019, P<0.01; 0.016±0.004 vs 0.109±0.019, P<0.01; 0.003±0.001 vs 0.109±0.019, P<0.01). Compared with that in the control group, the mean optical densities (ODs) of DMT1-positive cells in the SN of rats exposed to 15, and 20 mg/kg Mn2+ were significantly higher (0.062±0.004 vs 0.015±0.007, P<0.01; 0.116±0.064 vs 0.015±0.007, P<0.01). The mean ODs of FP1-positive cells in the SN of rats exposed to 5, 15, and 20 mg/kg Mn2+ were significantly lower than that in the control group (0.092±0.011 vs 0.306±0.081, P<0.01; 0.048±0.008 vs 0.306±0.081, P<0.01; 0.008±0.002 vs 0.306±0.081, P< 0.01). Rats exposed to 15 and 20 mg/kg Mn2+ had significantly higher expression of DMT1 mRNA in the SN than those in the control group (0.052±0.0126 vs 0.001±0.0004, P<0.05; 0.124±0.0299 vs 0.001±0.0004, P<0.05). However, rats exposed to 5, 15, and 20 mg/kg Mn2 had significantly lower expression of FP1 mRNA in the SN than those in the control group (0.059±0.0076 vs 0.162±0.0463, P<0.05; 0.033±0.0094 vs 0.162±0.0463, P< 0.05; 0.002±0.0007 vs 0.162±0.0463, P<0.05).

CONCLUSIONThe increased expression of DMT1 and reduced expression of FP1 may be involved in the processes of Mn2+ accumulation in the SN and dopaminergic neuron loss in rats with manganese-induced parkinsonism.

Animals ; Cation Transport Proteins ; metabolism ; Disease Models, Animal ; Manganese ; adverse effects ; Parkinsonian Disorders ; chemically induced ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; metabolism ; physiopathology

Objective:To investigate the protective effects of Ghrelin on LPS-induced apoptosis of human alveolar epithelial A549 cells,along with the possible molecular mechanisms.Methods: CCK-8 assay was used to examine the cell viability of A549 treated by LPS.Apoptosis of A549 cells was measured by TUNEL.NO(Nitric oxide)production was detected by NO-specific fluorescent probe 3-Amino,4-aminomethyl-2′,7′-difluoresceindiacetate(DAF-FM DA).Western blot was also performed to examine the expressions of iNOS(inducible nitric oxide synthase),AKT,ERK,p-AKT,p-ERK and apoptotic proteins,such as Bcl-2,Bax,and cleaved caspase-3.Results: LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration-and time-dependent manners accompanied with increased Bax and cleaved caspase-3 production,coupled with decreased Bcl-2 levels.Meanwhile,LPS promoted iNOS expression and the production of NO.Ghrelin pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression.TUNEL analysis showed that Ghrelin could decrease the apoptosis induced by LPS in A549(P<0.05).Simultaneously,LPS remarkably decreased the expression of p-AKT and p-ERK in A549 cells,which was abrogated by Ghrelin pretreatment.However,Ghrelin had no significant effect on NO production induced by LPS.Conclusion: Ghrelin reduces LPS-induced apoptosis of human alveolar epithelial cells partly through activating the AKT and ERK pathway,but the level of iNOS derived NO could not be reduced.

To compare the effects on hemodynamics of univentricular support with that of biventricular support on experimental ischemic biventricular dysfunction so as to provide experimental basis for clinical usage of the Luo-Ye pump. Eight canines were placed with a left ventricular assist device (LVAD; left atrial-aorta bypass) and a right ventricular assist device (RVAD; right atrial-pulmonary artery bypass). Left anterior descending coronary artery(LAD) was ligated, three minutes later, the proximal of right coronary artery (RCA) was ligated to establish animal madel of acute ischemic biventricular dysfunction. First start the LVAD, and then RVAD was started five minutes later. The hemodynamic data were recorded including central venous pressure(CVP), cardiac output (CO), mean artery pressure(MAP), and pulmonary artery pressure(PAP) and pulmonary capillary wedge pressure (PCWP). During biventricular assist devices (BVAD) the hemodynamics were improved remarkably, MAP increased from 37.4 +/- 8.8 mmHg to 84.2 +/- 9.7 mmHg (P < 0.01) (the normal level), CO increased from 0.82 +/- 0.1 L/min to 1.33 +/- 0.12 L/min (P < 0.01), CVP decreased from 14.6 +/- 2.3 cmH2O to 4.2 +/- 1.5 cmH2O (P < 0.01), PCWP decreased significantly from 14 +/- 3.9 mmHg to 1.6 +/- 0.9 mmHg. These data suggest that LVAD during biventricular dysfunction could not improve the hemodynamics to normal level. Howere BVAD could increase CO and MAP to normal level and decrease heart work and myocardial oxygen consumption, which could help to improve myocardial metabolism and myocardial function. Therefore, BVAD is the first choice in treating severe biventricular dysfunction which was not respond to drug therapy and intra-aortic balloon pump (IABP).
Animals ; Dogs ; Heart-Assist Devices ; Hemodynamics ; Myocardial Ischemia ; complications ; Ventricular Dysfunction ; etiology ; physiopathology ; surgery

Objective To test the effect of an APP in the adherence of inhalation medicines for children with asthma,improve the rate of inhalation medicines compliance,self management ability and the quality of life of children with asthma.Methods The research use self-control study.We use Medication Adherence Report Scale for Asthma (MARS-A) to test the adherence of inhalation medicines for children with asthma in outpatient department.After 2 months using the APP,the children with asthma may be re-tested by the MARS-A to compare the differences in medication adherence,asthma knowledge,use method and pulmonary function,etc.Finally,data analysis using paired t test.Results After using the APP,the inhalation medicines adherence rate is increased from 25.78 ％ to 68.75 ％,the awareness rate of patients and their caregivers are increased from 25 ％ to 65 ％,and the APP usage rate is 42.18％,there was significant difference (P＜0.01).Conclusion The APP can effectively improve the adherence of inhalation drugs,standardized medication management,guarantee treatment effect and improve the quality of life of children with asthma.It could also reducing medical costs and improving work efficiency and service quality,thus deserves promotion.

Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy ⁶⁰Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.