1.The effect of Guhong on the capability of brain to resist ischemia
Weihai XUN ; Liying CUI ; Pingping ZUO
Chinese Journal of Practical Internal Medicine 2006;0(20):-
Objective We investigated the effect of Guhong on the capability of brain to resist ischemia.Methods MCAO model was established in SD rats.TTC staining was performed in Guhong group with intraperitoneal injection and routine MCAO model group.Infarction volume was compared.Immunochemistry was performed to observe Caspase 3 expression in peri-infarct cortice of both of the groups.Results Guhong intraperitoneal injection significantly reduced the infarction volume(P﹤0.05).Caspase 3 expression was lower in Guhong group as compared with the model group.Conclusion Guhong may strengthen the capability of brain to resist ischemia.Anti-apoptosisinduced by Guhong may be the one of the underlied mechanisms.
2.An exploration of induction methodology and experimental duration of Graves disease animal model
Liping WU ; Bingyin SHI ; Liru XUN ; Liying GUO ; Jing YANG ; Li XU
Chinese Journal of Internal Medicine 2012;51(10):793-797
Objective To compare the efficacy of Graves disease animal models induced by thyroid stimulating hormone receptor (TSHR) plasmid DNA (pcDNA3.1-TSHR) and by TSHR A subunit recombinant adenovirus(Ad-TSHR289),and to investigate the influence of duration for preparing animal model induced by Ad-TSHR289 on Graves hyperthyroidism and its related indices.Methods The plasmid group and the adenovirus group were set up respectively.The plasmid group:21 female BALB/c mice were randomly divided into model group (n =12) and control group (n =9).The model group were injected intradermally with pcDNA3.1-TSHR 50 μg,once every 3 weeks,totally 3 times.Then 4 weeks after the last immunization,the mice were euthanized to obtain blood for testing TSHR antibody (TRAb),total T4,and thyroid tissue for histological examination.The controls were injected with the same dose of pcDNA3.1 in the same way.The adenovirus group:52 female BALB/c mice were divided into 10-week model group (n =8),14-week model group (n =10) and 18-week model group (n =8),and the respective controls (n =8,n =10,n =8) were set up.All model groups were injected intramuscularly with Ad-TSHR289,three times at three weekly intervals.Then the mice were euthanized at 4,8 and 12 weeks to test TRAb,total T4 level and to observe the change of thyroid histology.The controls were treated with the same dose of Ad-lacz in the same way.Another 8 mice were scheduled to test the dynamic variation of TRAb before and after the 3 times immunization.Results In the plasmid model group,only two of 12 mice developed weak antibody responses against TSHR,and no elevated total T4 level and no hyperplasia changes of thyroid were observed.In the 10-week model group,all mice had high level TRAb [(807.65 ± 136.33)U/L,Six-eighths mice had hyperthyroidism exhibited hyperplasia changes.In the 14-week model group,the TRAb level [(650.12 ± 192.88) U/L]and the incidence of hyperthyroidism (3/10) were lower than those in 10-week group.Histologically,the degree of thyroid hyperplasia lightened to a small extent,but its positive rate did not decline.In the 18-week model group,only 2 of 8 mice displayed slightly elevated TRAb level,and no mice showed increased total T4 level.Additionally,thyroid tissues of 2 mice were mildly abnormal.Compared with the model groups at different time,the change of antibody levels of the mice for TRAb dynamic observation exhibited the similar trend.Conclusions Being good at repeatability and high incidence of hyperthyroidism,the animal model of Graves disease induced by Ad-TSHR289 is still an ideal research tool presently.The duration of model ean be maintained 18 weeks,and 10 weeks is the best period to snstain characteristic of Graves disease.
3.Transplantation of bcl-2 gene-modified bone marrow mesenchymal stem cells improves cardiac function and angiogenesis in rabbit ischemic car-diac insufficiency model
Qing GAO ; Shuren LI ; Liying XUN ; Kexin YUAN ; Yuetao XIE ; Qianhui ZHANG ; Qingqing HAO ; Yi DANG ; Xiaoyong QI
Chinese Journal of Pathophysiology 2015;33(4):640-646
[ ABSTRACT] AIM:To investigate the effects of transplantation of bone marrow mesenchymal stem cells ( BMSCs) modified by bcl-2 gene on myocardial cell apoptosis, angiogenesis and cardiac function in the rabbit after acute myocardial in-farction ( MI) .METHODS:The rabbit BMSCs were isolated, cultured and purified in vitro.The BMSCs were transfected with adenovirus or adenovirus-Bcl-2.The rabbit model of MI was established by ligation of left anterior descending branch. The rabbits were injected with Ad-Bcl-2-BMSCs ( MI+Bcl-2-BMSCs group) , Ad-BMSCs ( MI+BMSCs group) and DMEM ( MI group) in infarction marginal zone 2 weeks after ligation.The cardiac function was evaluated by echocardiography.The apoptosis of myocardial cells was measured by TUNEL.The mRNA expression of VEGF was detected by real-time PCR.The expression of CD31 was examined by immunohistochemical staining, and new blood capillaries were counted at 4 weeks after BMSCs transplantation.The correlation of the above values with cardiac function was analyzed.RESULTS: The cardiac function was better, the apoptotic rate was lower, the mRNA expression of VEGF and the capillary density were higher in both MI+Bcl-2-BMSCs group and the MI+BMSCs group than those in MI group, and those in MI+Bcl-2-BMSCs group in-creased more obviously .The left ventricular ejection fraction ( LVEF) had a negative correlation with the myocardial cell ap-optosis rate.A positive correlation with the mRNA expression level of VEGF and the capillary density was also observed. CONCLUSION:The transplantation of BMSCs modified by bcl-2 gene significantly reduces the myocardial cell apoptosis, promotes angiogenesis, improves heart function of the rabbits with MI.
4.Effects of perindopril at different doses on cardiac function and ACE2/Ang-(1-9)/Ang-(1-7) axis of ischemic cardiac dysfunction rabbits
Xiao HAO ; Shuren LI ; Tiantian MENG ; Qing GAO ; Yi DANG ; Liying XUN ; Kexin YUAN ; Qianhui ZHANG ; Qingqing HAO ; Xiaoyong QI
Chinese Journal of Pathophysiology 2016;32(3):554-557,563
[ ABSTRACT] AIM:To investigate the different dose of perindopril on cardiac function in the rabbits with ische-mic cardiac dysfunction .METHODS:Male rabbits weighing 2.5~3.0 kg ( n=30) were randomly divided into 3 groups (n=10):high dose perindopril group (HD group), low dose perindopril group (LD group) and cardiac dysfunction group (CD group).The Left anterior descending coronary artery of the rabbits was ligatured for model preparation .In HD group, the rabbits were treated with perindopril split normal saline solution (1 g/L)2 mL· kg-1 · d-1 .In LD group, the rabbits were treated with perindopril split normal saline solution (0.33 g/L)2 mL· kg -1 · d-1.In CD group, the rabbits were treated with normal saline solution 2 mL· kg-1 · d-1 .Four weeks after treatment , the cardiac function was measured via echocardiography , the mRNA expression of angiotensin-converting enzyme 2 ( ACE2 ) and angiotensin type 2 receptor (AT2R) was analyzed by real-time PCR, serum angiotensin (Ang)-(1-9) and Ang-(1-7) levels were detected by ELISA. RESULTS:Compared with CD group , the cardiac function of the 2 groups treated with perindopril was significantly im-proved (P<0.01), and more improvement in HD group was observed than LD group (P<0.05).The serum angiotensin ( Ang)-(1-9) and Ang-(1-7) level and the mRNA expression of ACE 2 and AT2R in the 2 groups treated with perindopril were significantly improved (P<0.01).Compared with LD group, the mRNA expression of ACE2 and AT2R and the ser-um levels of Ang-(1-9) in HD group were significant improved (P<0.05), while no difference of serum Ang-(1-7) level was observed.Correlation analysis revealed that the improvement of the cardiac function was associated with serum Ang -(1-9) level, mRNA expression of ACE2 and AT2R (P<0.01), but has no significant correlation with serum Ang-(1-7) lev-el.CONCLUSION:High dose of perindopril may improve more cardiac function in ischemic cardiac dysfunction model in rabbits.The mechanism may relate to increasing serum Ang-(1-7) level to activate AT2R.
5.Influence of early regulating blood lipid on the prognosis and endothelial function in post-PCI acute coronary syndrom patients.
Shuren LI ; Xiaoyong QI ; Jianqing ZHANG ; Tianhong WANG ; Yi DANG ; Fuli HU ; Jie DONG ; Di WU ; Liying XUN ; Xiaoyun ZHAO
Chinese Journal of Practical Internal Medicine 2006;0(S1):-
Objective To investigate the influence of two different dose of atorvastatin on the prognosis and endothelial function in post-PCI acute coronary syndrom patients.Methods 92 post-PCI ACS patients were randomly divided into two groups,atorvastatin 20mg and atorvastatin 10 mg group.In each group the patients were treated with atorvasta- tin 20mg or 10mg respectively.After one month we add or decrease the dose of atorvastatin according to the blood lipid level.After 12 month the blood lipid level、FMD、NO、ET、NOS、UAP、AMI were compared between two groups. Results The clinical setting have no significant association between two groups before treating,After treated 1 and 12 month the TC,LDL-C level were significantly decreased as compared with the base level before treating in each group. After treated 1 month,in atorvastatin 20 mg group the TC,LDL-C level were significantly decreased and NO、NO/ET level were significantly higher than those in atorvastatin 10 mg group.During 12 month follow up the incidence of angina pectoris onset and rehospitalization were significantly higher in atorvastatin 10 mg group(P
6.Improvement of left ventricle remodeling by transplanting various autologous bone marrow stem cells
Shuren LI ; Xiaoyong QI ; Jianqing ZHANG ; Tianhong WANG ; Yi DANG ; Cunliang MENG ; Huiliang LIU ; Yingxiao LI ; Fuli HU ; Di WU ; Jie DONG ; Liying XUN ; Lihui GAO ; Fuchang JIN
Chinese Journal of Tissue Engineering Research 2008;12(47):9371-9377
BACKGROUND:Bone marrow stem cell transplantation can improve heart function and prevent ventricle remodeling.At present,the adult bone marrow stem cells used for transplantation primarily included bone marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs),and endothelial progenitor cells.The curative effects and precise mechanisms of transplantation of various bone marrow stem cells remain unknown.OBJECTIVE:To compare the effects of transplantation of autologous BM-MNCs and MSCs via the coronary artery on ventricle remodeling subsequent to acute myocardial infarction (AMI). DESIGN,TIME AND SETTING:Randomized controlled animal experiment performed at the Center for Clinical Research,Hebei Provincial People's Hospital,Electron Microscope Room,Hebei Medical University between March 2005 and December 2006.MATERIALS:Thirty-six male Jizhong pigs,were randomly divided into 4 groups:control group (n = 6),infarct model group (n = 10),BM-MNC group (n = 10),and MSC group (n = 10).METHODS:Porcine autologous BM-MNCs were isolated by gradient density centrifugation,and MSCs were obtained by adherence method.Prior to transplantation,both BM-MNCs and MSCs were colloidal gold labeled.Except the infract model group,pigs in the other 3 groups were developed into AMI models by oppressing the left anterior descending branch with balloon catheter.Ninety minutes after modeling,(6.0±1.3)×107 autologous BM-MNCs and (4.5±2.1)x 107 MSCs were respectively transplanted into pigs in the BM-MNC group and the MSC group via the coronary artery and cultured for 28 days.MAIN OUTCOME MEASURES:Observation of pathological changes of cardiac muscle tissue by light and electron microscope;Examination of cardiac function by ultrasonograph;Detection of the number of blood vessels and apoptotic myocardial cells,and expression of nuclear factor-κB (NF-κB) and troponin Ⅰ and its correlation to cardiac function by immunohistochemistry;Detection of mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cardiac tissue as well as its correlation to cardiac function by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS:In the MSC group,there was proliferation of a great deal of blood vessels as well as growth of abnormal cell masses around the coronary vessels,while the BM-MNC group exhibited the "budding" of many capillary vessels.Prior to transplantation,cardiac function indices were basically similar among each group (F = 1.550,P>0.05).Twenty-eight days after transplantation,left ventricular ejection fraction was significantly lower in the control,BM-MNC,and MSC groups than in the infarct model group (F = 5.30,P<0.05),while endocardial fractional shortening was significantly higher (F = 10.67,P<0.01).Compared with the infarct model group,the number of blood vessels in the infarct zone and infarct border zone was increased in the BM-MNC group (F=29.56-34.87,P<0.01) and had no apparent change in the MSC group.In the BM-MNC and MSC groups,apoptotic myocardial cells in the infarct zone and infarct border zone were significantly reduced (F=14.31-35.34,P<0.01 ) and troponin I expression rate was significantly increased (F=19.05,P<0.01 ),as compared with the infarct model group.In addition,NF-κB positive rate in the infarct border zone was significantly lower in the BM-MNC and MSC groups than in the infarct model group (F=19.05,P<0.01).VEGF gene expression level in the infarct border zone was significandy higher in the BM-MNC group than in the infarct model group and MSC group (F = 49.41,P<0.01).bFGF gene expression level in the infarct border zone was significantly higher in the MSC group than in the infarct model and BM-MNC groups (F=4.71,P<0.01).LVEF was negatively correlated to myocardial cell apoptosis rate and NF-κB level (r=-0.441 1,P<0.05;r=-0.579 6,P<0.01 ).LVEF was positively correlated to number of blood vessels,VEGF and bFGF expression (r=0.775,P<0.01;r=0.565 1,P<0.05;r=0.573 5,P<0.05).CONCLUSION:Transplantation of both autologous BM-MNC and MSC via coronary artery can improve the condition of left ventricular remodeling subsequent to myocardial infarction.The improvement of cardiac functions is related to the increase of blood vessels,VEGF and bFGF expression,the decrease of myocardial cell apoptosis and NF-κ B level in cardiac muscle tissues after stem cell transplantation.BM-MNC transplantation better promotes blood vessel proliferation and VEGF expression in the cardiac tissue but produces worse effects on bFGF gene expression than MSC transplantation.