ObjectiveTo investigate the expression of extracellular signalregulated kinase (ERK) and p38 mitogenactivated protein kinase （p38 MAPK） in autogenous vein grafts during vascular remodeling.MethodsAn autogenous vein graft model was established by transplanting the right jugular vein to infrarenal abdominal aorta in 80 Wistar rats. Vein graft samples were harvested 6 hours, 24 hours, 3 days, 7 days, 2 weeks, 4 weeks, 6 weeks and 8 weeks after surgery. Gene expression of ERK and p38 MAPK was measured by reverse transcriptionPCR. Western blot was used to detect the expression of protein products and phosphorylation protein products of ERK and p38 MAPK. Apoptosis of vascular smooth muscle cells (VSMCs) was determined by TUNEL. Proliferating cell nuclear antigen(PCNA) of VSMCs also was studied.ResultsThe expression of ERK1 mRNA and p38 MAPK mRNA increased considerably after surgery. ERK1 mRNA reached the peak on the 7th day 〔（33.2±14.2）%, P＜0.01〕, but p38 MAPK mRNA reached the peak on the second week after surgery 〔(58.8±26.2）%, P＜0.01〕. The expression of ERK1/2 detected by western blot reached the peak during 1 to 2 weeks and decreased gradually to normal level 6 weeks after surgery. The expression of p38 MAPK reached the peak during 2 to 4 weeks and decreased to 1/4 to 1/2fold 8 weeks after surgery. There was a positive relationship between ERK1 and PCNA(r=0.759 6，P＜0.01) and a positive relationship between p38 MAPK and apoptosis(r=0.892 2，P＜0.01). ConclusionActivation of MAPK system exists in autogenous vein grafts and it may become a new target for the therapy of stenosis after vein grafts.
Objective To study the intervention effect of ginkgo biloba extract（GBE） on airway and vascular remodeling in rat model of chronic obstructive pulmonary disease(COPD).Methods Forty wistar rats were randomly divided into group A，B，C and D.The rat model of COPD were established by intratracheally injection of lipopolysaccharide and exposure to cigarette smoke in groups B，C and D.Groups C and D were given intraperitoneally injection with 40 mg/kg GBE respectively from day1 to day14 and day29 to day42.Forty-three days later，the rats were sacrificed for lung pathological examination.Results Group B，C and D all showed pathological changes characteristic of COPD to different extent.The average area and standard number of alveoli showed significant difference between each groups（all Plt;0.01）.The structure of bronchiole walls in group C and D show mild changes.The ratio of bronchial smooth muscle thickness to bronchial wall thickness and bronchial wall area to bronchial area of group C and D showed significant difference when compared with group A and B（all Plt;0.01）.The vascular smooth muscle cell of group C and D had mild hyperplasia and the vascular wall had slightly thickened.The ratio of vascular smooth muscle thickness to vascular wall thickness and vascular wall area to vascular area in group C and D showed significant difference when compared with group A and B（all Plt;0.01）.Conclusion GBE has inhibitory effects on airway and vascular remodeling in rats model of COPD.
Objective To investigate the effects of smoking intensity, duration and cessation on mRNA and protein expressions of matrix metalloproteinase-9 ( MMP-9) in tracheal epitheliumof rats, and the relationship between smoking or smoking cessation and airway remodeling in chronic obstructive pulmonary disease ( COPD) . Methods Forty Wistar rats were randomly divided into 5 groups, ie. a normal control group, a long termheavy smoking group, a short termheavy smoking group, a long termlight smoking group,and a smoking cessation group which was exposed to room air for 10 weeks after long term heavy smoking.The expressions of MMP-9 mRNA and protein in tracheal epithelium of rats were detected by in situ hybridization and munohistochemistry respectively. Results ( 1) The pathological changes of emphysema were observed in the lung tissue of every smoking rat, and were most sever in the long term heavy smoking group. ( 2) Compared with the normal control group [ ( 0. 88 ±0. 88) PU, ( 2. 80 ±1. 66) PU] , the expressions of MMP-9 mRNA and proteins in tracheal epithelium were remarkable elevated in the long term heavy smoking group [ ( 22. 01 ±2. 86) PU, ( 20. 81 ±2. 46) PU] , the short term heavy smoking group [ ( 14. 94 ±3. 46) PU, ( 13. 68 ±2. 00) PU] , the long term light smoking group [ ( 6. 92 ±2. 71) PU,( 8. 84 ±1. 80) PU] and the smoking cessation group [ ( 19. 00 ±3. 36) PU, ( 14. 82 ±1. 74) PU] ( P lt;0. 01) . Compared with the long term heavy smoking group, the expressions of MMP-9 in tracheal epithelium were decreased in other three smoking groups ( P lt; 0. 05) . Conclusions Smoking could increase the expression of MMP-9 in tracheal epithelium and cause trachea damage and remodeling with intensity and duration in rats. Smoking cessation could decrease the MMP-9 expression and alleviate trachea remodeling,suggesting its role in the prevention of COPD.
Objective To study the concentration of neurotrophins( including NGF, BDNF, NT3 and NT4) in the lung of SD rats infected by respiratory syncytial virus( RSV) , and to explore the relationship between the concentration of the neurotrophins, airway hyperresponsiveness and airway neural plasticity.Methods Twenty SD newborn rats were randomly divided into a control group and a RSV-infected group with ten rats in each group. The RSV-infected group were infected with 5 ×104 TCID50/0. 1 mL RSV each week. After 8 weeks, the bronchial responsiveness of the SD rats was assessed. The bronchial inflammation was assessed by HE staining with left lung. Synaptophysin and neurofilament expressions in the lung of SD rats were assayed by the immunohistochemistry staining. In situ hybridization was used to detect the RSV RNA in the lung. The concentration of neurotrophins in the lung of SD rats were detected by ELISA. Results The RSV-infected group showed elevated airway hyperresponsiveness and more inflammatory cells infiltrated in the lung; In situ hybridization showed positive signal of RSV RNA in lung interstitium of the RSV-infected rats. Synaptophysin and neurofilame levels in the airway were increased in the RSV-infected group. Supernatant levels of NGF and BDNF were significantly increased compared with the control group ( P lt;0. 05) . The NT3 and NT4 levels had no significant difference in all groups. The expressions of NGF and BDNF were positively related to the expressions of synaptophysin( r1 = 0. 892, r2 = 0. 995, P lt; 0. 05) and neurofilament( r1 = 0. 949, r2 =0. 936, P lt;0. 05) , also positively related to the airway hyperresponsiveness ( r1 =0. 929, r2 = 0. 910, P lt; 0. 05) . Conclusion RSV infection results in increased expressions of NGF and BDNF in the lung, which are correlated to the change of airway neural plasticity and airway hyperresponsiveness.
【Abstract】 Objective To investigate the effect of allogeneic bone marrow-derived mesenchymal stem cells ( BMSCs) transplantation on the airway inflammation and airway remodeling in chronic asthmatic mice. Methods Forty female BALB/c mice were equally randomized into four groups, ie. a normal control group, a BMSCs control group, an asthma model group, and a BMSCs transplantation group. BMSCs were generated from male donor mice, then the mice in the asthma model group and the BMSCs transplantation group were sensitized and challenged with OVA to establish chronic asthmatic mice model. Hematoxylin and eosin staining and Alcian blue-periodic acid-Schiff staining were used to analyze the effects on airway inflammation and airway remodeling after BMSC engraftment. The number of CD4 + CD25 + regulatory T cells in spleen was detected by flow cytometry. Results In lungs of the asthmamodel group, there were intensive inflammatory cells infiltration around airway and blood vessels, goblet cell proliferation, epithelial desquamation, patchy airway occlusion by hyperviscous mucus, and hypertrophy of airway smooth muscle.Airway inflammation and airway remodeling were significantly relieved in the BMSCs transplantation group.There was no obvious inflammatory cells infiltration in the airway and airway remodeling both in the normal control group and the BMSCs control group. The number of CD4 + CD25 + regulatory T cells in spleensignificantly decreased in the asthma model group compared with the two control groups ( P lt; 0. 05) , and significantly increased in the BMSCs transplantation group compared with the asthma model group ( P lt;0. 05) . There was no significant difference in the number of CD4 + CD25 + regulatory T cells in spleen betweenthe control groups and the BMSCs transplantation group. Conclusion BMSCs engraftment can up-regulate CD4 + CD25 + regulatory T cells and relieve airway inflammation and airway remodeling in asthmatic mice.
Objective To evaluate the effects of oxidative stress in the airway inflammation and remodeling of high-fat diet induced obese mice with asthma. Methods Sixty female C57 /6J mice were randomly divided into four groups, ie. an asthma group, an obese group, an obese asthma group, and a control group. The mice in the asthma group were sensitized and challenged with ovalbumin ( OVA) and fed with normal diets. The mice in the obese group were fed with high-fat diets. The mice in the obese asthma group were sensitized and challenged as the asthma group, and fed as the obese group. The mice in the control group were sensitized and challenged with normal saline and fed with normal diets. After 12 weeks, bronchoalveolar lavage fluid ( BALF) were collected for total and differential cell count. IL-6 and 8-iso-prostaglandin F2α ( 8-iso-PGF2α) in lung tissue homognate were detected by ELISA. The pathological changes were observed under light microscope by HE staining. Meanwhile the remodeling indices including total bronchial wall area ( WAt) , smooth muscle area ( WAm) , and bronchial basement membrane perimeter ( Pbm) were measured. Results In comparison with the obese group and the asthma group, the leukocytes and eosinophils in BALF, WAt/ Pbm, and IL-6 in lung tissue increased significantly in the obese asthma group ( P lt; 0. 05) . 8-iso-PGF2αin lung tissue increased in sequence of the control group, the obese group, the asthma group, and the obese asthma group significantly. Pearson correlation analysis showed that leukocyte in BALF, WAt/ Pbm, and IL-6 were in positive correlation with 8-iso-PGF2α( r =0. 828, 0. 863, 0. 891, respectively, P lt;0. 01) . Conclusion Oxidative stress is involved in the airway inflammation and remodeling of obese asthma mice with high-fat diets.
Abstract： Objective To study thoracic bone remodeling and clinical effects after minimally invasive correctionfor pectus excavatum （PE） in children. Methods A retrospective review was conducted of a prospectively gathereddatabase of 74 child patients who underwent minimally invasive repair of PE at General Hospital of Beijing MilitaryDistrict between Apr. 2009 and Sept. 2010. Of the patients, 63 were males and 11 females; the age was（ 11.90±8.50）years, 11 patients ＜ 10-year-old among them. Under general anesthesia, two incisions were made at the side midaxillaryline, and the introducer created a tunnel at the trans-substernum and shaped the thoracic cavity. The bar was then insertedinto the retrosternum by video-assistant thoracoscopic monitoring. All patients were checked by chest computerizedtomography（CT） scan preoperatively and one week after operation, with three-dimensional reconstruction. The sagittalview was by means of the center line of the body of thoracic vertebrae. The distance between the sternum and the frontaledge of the body of thoracic vertebrae was measured and the return of displacement of the heart was observed. ResultsAll 74 operations were successful; there were no deaths. One bar was used for 66 patients （89.19%）, while two barswere used for the other 8 patients （10.81%）. Comparing the results of pre- with post-correction, for patients youngerthan 10 years（n=11） who had one bar placed, the inferior extremity of the manubrium and midsternum displacedforward to 3.76-22.92 mm. For 11-17 year-old patients（n=55） , anterior displacement of only the middle and lowerpart of the midsternum was 2.08-10.42 mm. There was a significant difference between the two groups in the inferiorextremity of the midsternum displaced（t=14.24, P ＜ 0.05）. For those patients with two bars, the inferior extremity ofthe manubrium and the midsternum were each displaced forward 4.19-15.03 mm at 7 d after operation. At 7 d after operation,the cardiac position in 65 patients（ 87.84%） of the all putted back by CT image. The chest shape of patients who received twobars was better than that of patients who received one bar. After 6-23 months of follow-up, it was pre-operative symptomsdisappeared in the patients, chest shape was satiation. Cardiac position in all patients was completely recovered. ConclusionThe thoracic bones of children with PE after minimally invasive repair have favorable remodeling. Older children requiregreater strength of support of the sternum during correction, but still realize a satisfactory therapeutic effect.
Abstract： Objective To investigate the effects of βreceptor blocker on intraventricular pressure gradient and left ventricle remodeling after valve replacement for critical aortic stenosis. Methods Fifty-six patients with critical aortic stenosis underwent aortic valve replacement surgery from January 2008 to January 2010 in the First Affiliated Hospital of Zhengzhou University. Thirtytwo of them who were followed up were selected to be enrolled in this study. The patients were divided into two groups under the same basis of clinical features. Twelve patients in the experimental group received oral βreceptor blocker (Metoprolol, 6.2525.00 mg once, twice daily). The rest 20 patients in the control group had no βreceptor blocker. The various indicators of ultrasound cardiogram (UCG) shortly after operation (within a week) and long after operation (6-24 months) were compared between the two groups. Results No death occurred in both groups, and chest distress, shortness of breath and other symptoms were obviously alleviated. Although left ventricular endsystolic dimension (LVESD) and left ventricular outflow tract dimension (LVOTD) of both groups increased 6-24 months after operation, compared with the early postoperative period, only the increase of LVOTD in the experimental group showed statistical difference (t=-47.937, P=0.001). In both groups, interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), filament band velocity of left ventricular outflow tract (V), intraventricular pressure gradient (G) and left ventricular mass index (LVMI) of the later period after operation were significantly lower than those of the early postoperative period. All these indicators in the experimental group showed significant differences (t=7.781, P=0.001；t=5.749, P=0.001; t=2.637, P=0.023; t=7.167, P=0.001; t=100.061, P0.001), while only V, G， and LVMI showed statistical differences in the control group (t=4.051, P=0.001; t= 4.759, P= 0.001; t=-0.166,P=0.001). EF in the experimental group also indicated significant difference compared with early period after aortic valve replacement (t=-6.621, P=0.001). EF between two groups indicated no significant difference (t=-0.354,P=0.726). But differences between the two groups in LVEDD, IVS, G， and LVMI were all statistically significant in the later period after surgery (t=-2.494, P=0.018; t=-3.434, P=0.002;t=-2.171,P=0.038; t=-2.316, P=0.028). Conclusion β-receptor blocker is a safe and reliable drug for those patients who have undergone aortic valve replacement surgery for critical aortic stenosis, and can decrease significantly the residual intraventricular pressure gradient and accelerate left ventricular cardiac remodeling.
Objective To investigate the dynamic changes of vascular adventitia and collagen distribution in the vein graft restenosis model, and evaluate the effects of adventitia and collagen distribution on intimal hyperplasia and vascular remodeling. Methods The pig autogenous vein grafts restenosis model from 18 longwhite pigs were created. 18 pigs were divided into 3 groups: 7th day group after operation, 30th day group after operation and 45th day group after operation according to animals harvested after surgery. The preoperative graft was as control group. According to HE and Masson staining slices, the vascular thickness, cell density, collagen distribution and vascular remodeling were investigated by histomorphometrical approach. Results In 7th day group after operation, the neointima formed and continuously thickened. The thickness and cell density of adventitia increased gradually, and the collagen of adventitia and neointima gradually increased, the luminal area gradually decreased after operation, but have no significant difference with control group（F=2.03,P=0.091）. The residual restenosis rate increased inversely（F=5.16,P=0.033）. Remodeling index and external elastic lamina area (EELA) slightly increased. In 30th day group after operation, the neointima thickened significantly, the thickness and cell density of adventitia reached the peak. There were a significant increase in the collagen of neointima, and the collagen of adventitia reached maximum. The luminal area and inter elastic lamina area(IELA) reduced distinctly as compared with 7th day group, the residual restenosis rate increased significantly（F=6.63,P=0.018）, but remodeling index and EELA decreased distinctly as compared with 7th day group after operation. In 45th day group after operation, the thicknessof neointima reached maximum, but the cell density of adventitia reduced distinctly compared with 30th day group after operation（F=6.91, P=0.015）. The collagen of neointima reached maximum, but the collagen of adventitia were smaller than those in 30th day group after operation, and there were some local fibrosis in adventitia. The luminal area, remodeling index, IELA and EELA reached minimum, but the residuum restenosis rate reached maximum. Conclusion Vein grafts restenosis is resulted by intimal hyperplasia and vascular remodeling. The thickness and fibrosis of adventitia and rearrangement of collagen are the important factors on intimal hyperplasia and vascular remodeling, which takes part in and accelerate the course of vein restenosis.
Objective Engineer heart tissue (EHT) was constructed with mesenchymal stem cells (MSCs) and poly lacticacidCOglycolic acid (PLGA), and grafted onto the surface of myocardial infarction rats. We hypothesized that great omentum wrapping would increase EHT blood supply and ameliorate EHT microenvironment which is in favor of cardiac collagen remodling and heart function. We hope that omentun wrapped EHT could provide a valuable strategy for surgically myocardial infarction therapy. Methods MSCs were isolated from SD rats.Eight weeks after SD rats were subjected to left anterior descending (LAD) ligation, 18 rats were enrolled and divided into three groups, group A(n=6): great omentum wrapped MSCsPLGA EHT implantation; group B (n=6):MSCsPLGA EHT implantation; control group (n=6): the myocardial infarction; the sham group (n=6): only opened and closed chest, underwent LAD ligation, but no EHT implantation. Four weeks after transplantation, the following variables were evaluated: specimen stained with picrosirius red, left ventricle function evaluated by echocardiography, infarction ventricular wall motion by color kinesis (CK). Results Hearts of group A showed significantly less fibrosis than group B and control group (Plt;0.05). Infarction ventricular wall motion assessed by CK indicated significantly improvement in group A compared with group B and control group (Plt;0.05). Four weeks after transplantation, cardiac echocardiography showed left ventricle ejection fraction was lower in control group and group B compared with group A (Plt;0.05). Conclusion Transplantation of MSCsPLGA EHT with great omentum wrapping ameliorated infarction ventricular collagen remodeling, ameliorated infarction ventricular wall motion and preserved left ventricular function.