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 explore the effects of prolonged Aspergillus fumigatus spores inhalation on airway inflammation and remodeling in rats with chronic obstructive pulmonary disease（COPD）.Methods Fifty Wistar rats were randomly divided into group A，B，C，D and E，(n=10 in each group) and group E was served as normal control.In group A，B，C and D，COPD models were established by intratracheal administration of lipopolysaccharide (LPS) combined with cigarette smoke exposure.The rats in group A，B and C were given intranasal inhalation of 1×106cfu spores，1×103cfu spores and 100 mL saline twice a week for consecutive 5 weeks，respectively，while the rats in group D were given no treatment.Bronchoalveolar lavage fluid(BALF) were collected for total and differential cell count，and interleukin-8（IL-8） and transforming growth factor-b(TGF-b) concentration measurement.The pathologic changes of lung tissue were observed by HE，PAS and Masson stainings.Results Pathological changes characteristic of COPD were found in group D.The total cell count，the percentage of neutrophile and lymphocyte in BALF in group A and B were higher than those in group C and D(all Plt;0.01).IL-8 and TGF-b in BALF in group A and B were higher than those in group C and D(all Plt;0.01).The pathologic score of airway inflammation in group A was higher than those in group B，C and D(all Plt;0.01)：The thickness of airway wall(WAt/Pbm) and airway smooth muscles(WAm/Pbm)，the collagen deposition in the total airway wall(WCt/Pbm) and in the outer airway wall(WCo/Pbm) and the percentage of goblet cells to epithelial cells in group A and B were higher than those in group C and D(all Plt;0.01).In group A and B，IL-8 was positively correlated with the percentage of neutrophile(r=0.856，Plt;0.01)，the pathologic score of airway inflammation(r＝0.884，Plt;0.01)，and the percentage of goblet cells to epithelial cells (r=0.702，Plt;0.05)，respectively.TGF-b was positively correlated with WAt/Pbm，WCt/Pbm，WCo/Pbm and the ratio of goblet cells to epithelial cells (r=0.706，Plt;0.05：r=0.802，Plt;0.01：r=0.876，Plt;0.01：r=0.713，Plt;0.05).Conclusion Prolonged inhalation of Aspergillus fumigatus spores can aggravate the airway inflammation and remodeling in rats with 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.
【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.
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 evaluate the effectiveness and prospect of nontransplantation surgical cardiac remodeling for endstage cardiac valve disease by performing the remodeling operation (including anatomical and functional remodeling) after strict perioperative adjustment for endstage cardiac valve disease. Methods We retrospectively analyzed the clinical data of 31 patients, including 14 males and 17 females, with endstage cardiac valve disease who were treated with surgical cardiac remodeling operation from December 2005 to July 2009 in the 2nd Hospital of Anhui Medical University . Their age ranged from 27 to 74 years with an average age of 40.4 years. Continuous renal replacement therapy (CRRT) was carried out 3 days before surgery in all patients and intraaortic balloon pumping (IABP) was performed 1-3 days before operation in 9 patients. Among the patients, there were 13 patients of mitral valve replacement (MVR), 7 patients of aortic valve replacement (AVR), 4 patients of tricuspid valve replacement (TVR), and 7 patients of double valve replacement (DVR). At the same time, all patients underwent ventricular or atrial volume reduction operation, including 19 patients of left atrial partial excision or plication, 7 patients of partial left ventricular excision, 5 patients of left atrial and left ventricular volume reduction operation, 21 patients of partial right atrial excision, and 3 patients of partial right ventricular excision. Besides, there were 5 patients of De Vega plasty, 14 patients of annuloplasty and3 patients of coronary artery bypass grafting (CABG). The echocardiogram was used to observe the change of heart function, atrium and ventricular in patients on postoperative and follow -up period. Results After surgery, one patient died of low cardiac output syndrome, and one other patient gave -up because of incision and mediastinum infection after reoperation for hemorrhage. Twentynine patients were followed -up for 3 to 12 months with 1 case lost. During the follow- -up, 3 patients died, of whom 2 died of deterioration of heart function and 1 died of sudden stroke. In the 12th month during the follow -up, heart function of all other 25 patients showed obvious improvements with 12 classⅠ, 7 classⅡ, 3 classⅢ and 3 classⅣ heart function according to NYHA classification. At the end of the follow -up, ejection fraction (5400%±800% vs. 2500%±300%) and cardiac index ［3.30±0.50 L/(min·m2) vs. 1.10±0.30 L/(min·m2)］ were significantly higher than those before operation (P＜0.05), whereas left ventricular end diastolic diameter (5200±1000 mm vs. 9500±1200 mm) and left atrial diameter (3900±800 mm vs. 7000±1200 mm) both decreased significantly than those before operation (P＜0.05). Conclusion Cardiac remodeling operation for endstage cardiac valve disease after active adjustment and preparation can achieve similar results to operation for severe valve diseases, providing a new choice for endstage heart disease.
Objective To evaluate the effect of smooth muscle cell transplantation on myocardial interstitial reconstruction shortly after myocardial infarction. Methods A total of 48 female Wister rats were randomly divided into two groups with the random number table, the control group (n=24) and the smooth muscle cell transplantation group (n=24). The left coronary artery was ligated to set up the myocardial infarction animal model. An amount of 05 ml phosphate buffered saline(PBS) containing 1×106 smooth muscle cells or 0.5 ml PBS without cells was injected into the injured myocardium immediately. By immunoblot and reverse transcriptionolymerase china reaction (RT-PCR), we observed the amount of protein and mRNA of matrix metalloproteinase2(MMP-2), matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloprotease-3 (TIMP-3) in the myocardium of the rats. Results The transplanted smooth muscle cells survived well. Compared with the control group, myocardial TIMP3 mRNA (1.06±0.22 vs. 0.81±0.19, t=－2.358, P=0.033) and protein content (3.33±0.53 vs. 1.63±0.47, t=－6.802, Plt;0.001) were significantly increased in the transplantation group. Myocardial MMP-2, MMP-9 mRNA (0.49±0.12 vs. 1.16±0.18, t=8.453, Plt;0.001; 0.45±0.12 vs. 0.80±0.11, t=5.884, Plt;0.001) and protein content (3.98±1.08 vs. 6.05±0.91, t=4.139, P=0.001; 0.39±0.14 vs. 0.57±0.17, t=2.409, P=0.031) [CM(1585mm]were significantly reduced in the transplantation group compared with the control group. Conclusion transplanted smooth muscle cells can survive well in the infarction myocardium and can increase the amount of myocardial TIMP-3 mRNA and protein content and reduce myocardial MMP-2, MMP-9 mRNA and protein content, which is an effective way to prevent harmful cardiac remodeling.
Atrial fibrillation(AF) is the most common disorder of cardiac rhythm. It has a high morbidity, mortality and disability, and serious impact on quality of life of patients. It is demonstrated that atrial remodeling which includes atrial electrical remodeling and structural remodeling,are the central contributors to the development and selfperpetuating of AF. However, The mechanisms that underlie the atrial remodeling process in AF have not yet been completely elucidated. New strategies for the prevention and termination of AF should build on our knowledge of the mechanisms of atrial remodeling. Medication for the reversal of atrial remodeling may be the new target for the treatment of AF. At present, drugs that target atrial remodeling have already obtained fruitful results in the experimental and clinical investigations. Now some recent advancements of this area is reviewed in this article.