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1.
Acta Pharmaceutica Sinica ; (12): 2171-2176, 2022.
Article in Chinese | WPRIM | ID: wpr-936586

ABSTRACT

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

2.
Braz. j. med. biol. res ; 54(10): e10653, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285657

ABSTRACT

Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.


Subject(s)
Humans , Caveolin 1/genetics , Glioma , Cell Line, Tumor , Cell Proliferation , Neovascularization, Pathologic
3.
Acta Pharmaceutica Sinica ; (12): 570-576, 2021.
Article in Chinese | WPRIM | ID: wpr-873779

ABSTRACT

Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.

4.
Herald of Medicine ; (12): 193-197, 2019.
Article in Chinese | WPRIM | ID: wpr-744213

ABSTRACT

Objective According to the clinical medicinal crystal form———form γ of levonorgestrel, to establish the quantitative analysis method for levonorgestrel form γ by powder X-ray diffraction (PXRD) . Methods Firstly, single crystal X-ray diffractometry and powder X-ray diffractometry were used to confirm that the prepared levonorgestrel form γ was 100% polymorphic purity, which provided a standard sample for quantitative analysis by single peak method; then, the standard samples of different quality levonorgestrel form γ for powder X-ray diffraction were weighed, the peak intensity values of characteristic diffraction peaks d = 6.4 , d = 6. 1  and d = 5. 6  of form γ as quantitative parameters selected, a linear relationship between the peak intensity value and the quality of form γ was established; finally, the content of levonorgestrel form γ was quantitatively analyzed. Results The peak intensity values of characteristic diffraction peaks d = 6.4 , d = 6.1  and d = 5.6  of levonorgestrel form γ and the quality showed a good linear relationship.In the range of form γ masses of 5 mg to 50 mg, the regression linear equations wereY = 459.59X+5 536.5, R2 = 0.993 0, Y = 430.03X+6 867.6, R2 = 0.990 5,Y = 615.95X+ 6 209.5, R2 = 0.990 8,respectively. Conclusion The method is simple, rapid, accurate and reliable, it can be used as quality control method for levonorgestrel polymorphs.

5.
Herald of Medicine ; (12): 183-187, 2019.
Article in Chinese | WPRIM | ID: wpr-744211

ABSTRACT

Objective To study the gastrointestinal absorption process of three letrozole polymorphs in rats, and evaluate the different pharmacokinetics parameters of different polymorphs. Methods A total of 18 SD rats were given the different letrozole polymorphs. Then the high-performance liquid chromatographic method was used for the determination of plasma concentration of letrozole in these SD rats.Finally the pharmacokinetic parameters among the different polymorphs were calculated. Results Cmax of letrozole crystal form I, crystal form II and crystal form III were (9.247± 4.612) ,(23.387± 9.049) and (15.682±1.589) mg·L-1, respectively, and AUC0→t were(198.115±47.014) ,(476.641±125.467) and (271.817±41.068) mg·L-1·h,respectively. Conclusion The different crystal forms of letrozole result in different plasma concentration in SD rats. Crystal form II may be its preponderant polymorphs which deserves further research and development.

6.
China Pharmacy ; (12): 1044-1048, 2018.
Article in Chinese | WPRIM | ID: wpr-704732

ABSTRACT

OBJECTIVE:To establish rapid method for content determination of cryptotanshinone in Salvia miltiorrhiza. METHODS:The content of cryptotanshinone in sample was determined by HPLC(as reference value). AOTF-NIDRS combined with PLS was used to establish quantitative correction model for the content of cryptotanshinone in S. miltiorrhiza. According to the results of content determination of cryptotanshinone in samples,35 samples of medicinal material were collected. First-order derivative combined with smoothing filter coefficient method was used to pretreat spectrum,and optimal band range for content determination of cryptotanshinone in sample ranged 1 250-2 150 nm. RESULTS:Methodology validation of content determination of cryptotanshinone in sample was in line with the requirements. Correction mean square deviation of quantitative correction model of cryptotanshinone was 0.014 6,and predicted mean square deviation was 0.022 3,coefficient of association was 0.976 6. The internal verification deviation was 2.41% and the external verification deviation was 4.06%. CONCLUSIONS:This method is rapid,accurate,simple and pollution-free.It can be used for rapid content determination of cryptotanshinone in S.miltiorrhiza.

7.
Acta Pharmaceutica Sinica ; (12): 1918-1923, 2017.
Article in Chinese | WPRIM | ID: wpr-779807

ABSTRACT

Nimodipine is a selective calcium channel antagonist of cerebral vessels smooth muscle and also has polymorphs. It hasn't been reported that different crystal forms influence the metabolism process in huge animals like rhesus monkeys in vivo. This article may provide reference in the control of the quality of nimodipine and quality consistency evaluation. The powder X-ray diffraction (PXRD) method was used to identify different crystal forms and the dissolution test in vitro was used to detect the dissolution. The LC-MS method of assay nimodipine in rhesus monkey plasm was established to determine pharmacokinetics characters of different tablets from different crystal forms in rhesus monkey in vivo. As a result, the tablets inherit difference crystal forms and the dissolution of reference tablets is 1.3% higher than crystal tablets. However, the maximal blood concentration (Cmax) of crystal tablet was 37.3% higher than reference tablet and AUC of crystal tablet was 29.8% higher than reference tablet. After administrated 2.5 mg·kg-1 orally, calculated pharmacokinetics characters were observed as following:Cmax was 381.4 ±327.3 and 178.0 ±214.8 μg·L-1; AUC0-t was 853.1 ±500.7 and 646.5 ±430.3 μg·L-1·h respectively. The serum concentration result of different nimodipine tablets in rhesus monkeys in vivo suggests that polymorphs has a significantly distinction, which points out that controlling the crystal forms of nimodipine is essential to ensure the therapeutic efficacy. It is essential to execute quality consistency evaluation.

8.
Herald of Medicine ; (12): 1225-1230, 2017.
Article in Chinese | WPRIM | ID: wpr-659354

ABSTRACT

Objective To study polymorphism of the free radical scavenger edaravone and to find the one which has good advantages to the clinical medication. Methods Preparation of four forms of edaravone through kinds of physical or chemical methods. These polymorphs were characterized by single crystal X-ray diffraction method (SXRD), powder X-ray diffraction method (PXRD), differential scanning calorimetry method (DSC), infrared spectrum method (IR) and melting point method (MP);a variety of influence factors experiment were used to research the stability of polymorphs. Solid edaravone in different forms were orally administered to SD rats respectively, the plasma concentration of the drug was determined by HPLC, and the pharmacokinetic characteristic of different forms was compared according to the HPLC results. Results Four forms(form A, form B, form C, form D) and the preparation of pure crystal forms were obtained by crystal screening technology. These polymorphs were identified by PXRD, DSC and IR. The edaravone polymorphs have an influence on the stability and pharmacokinetic. Conclusion Edaravone research provideds a variety of crystal material composition, preparation methods, stability, solubility and pharmacokinetic characteristic, and form A has been proved of good advantage one. This research provides data and technology support for choice of preponderant pharmaceutical polymorphs and drug quality standard improvement.

9.
Herald of Medicine ; (12): 1225-1230, 2017.
Article in Chinese | WPRIM | ID: wpr-657366

ABSTRACT

Objective To study polymorphism of the free radical scavenger edaravone and to find the one which has good advantages to the clinical medication. Methods Preparation of four forms of edaravone through kinds of physical or chemical methods. These polymorphs were characterized by single crystal X-ray diffraction method (SXRD), powder X-ray diffraction method (PXRD), differential scanning calorimetry method (DSC), infrared spectrum method (IR) and melting point method (MP);a variety of influence factors experiment were used to research the stability of polymorphs. Solid edaravone in different forms were orally administered to SD rats respectively, the plasma concentration of the drug was determined by HPLC, and the pharmacokinetic characteristic of different forms was compared according to the HPLC results. Results Four forms(form A, form B, form C, form D) and the preparation of pure crystal forms were obtained by crystal screening technology. These polymorphs were identified by PXRD, DSC and IR. The edaravone polymorphs have an influence on the stability and pharmacokinetic. Conclusion Edaravone research provideds a variety of crystal material composition, preparation methods, stability, solubility and pharmacokinetic characteristic, and form A has been proved of good advantage one. This research provides data and technology support for choice of preponderant pharmaceutical polymorphs and drug quality standard improvement.

10.
Herald of Medicine ; (12): 930-934, 2015.
Article in Chinese | WPRIM | ID: wpr-467293

ABSTRACT

Objective To establish a method for qualitative identification of polymorphs in pharmaceutical solid preparations of active pharmaceutical ingredients ( API ) . Methods We obtained the powder diffraction patterns of the polymorphic drug substance like nimodipine and roxithromycin in solid preparation material and completed quantitative identification for polymorphs by the quantitative detection and using PXRD technology, deduction calculation through the powder X-ray diffraction and comparing with standard diagram. Results Through the analysis of nimodipine and roxithromycin which came from 27 batches of solid preparations from 11 different manufacturers, and comparing to the standard patterns of pure polymorphs, the quantitative identification of different crystalline states of API in pharmaceutical preparations had been established. Conclusion The qualitative detection method for polymorphs of API in pharmaceutical preparations by powder X-ray diffraction has wide applicability and high accuracy, which can be used to identify the polymorphism of API in solid preparation,and also used to control the quality of solid preparations commonly as a qualitative analysis method.

11.
Article in Chinese | WPRIM | ID: wpr-463743

ABSTRACT

Objective To evaluate the efficacy and safety of open occluded coronary artery branch through outside stent balloon expansion technique.Methods A retrospective analysis of 26 patients,26 interventional treat-ment of coronary bifurcation lesions were taken.All patients initially used conventional interventional techniques, branch reserve protection guidewire and main branch stent.When branch occlusion occured during operation and failed again through guidewire,small outer diameter of the balloon branch guidewire which was squeezed could be used to branch opening.The blocked branch opening was expanded outside of the stent,and the balloon was expanded after the guide wire enter into branch again.The main branch/branches kissing balloon inflation or main branch /branch double stenting would be used when necessary.Results Among 26 cases of bifurcation branch occlusion,25 cases successfully completed the outer stent balloon,achieved a branch balloon expansion after reentry guidewire,saved blocked branches and the rate of success was 96.2%,and 6 cases of the main branch and the branch kissing balloon dilatation,2 cases of remedial double stenting.Following -up for 1 -12(5.3 ±6.8)months after operation in 25 cases of patients,there was no death and myocardial infarction and other adverse cardiovascular events.Conclusion Out-side stent balloon expansion technique can improve the success rate of coronary occlusion branch opening,and it have fewer complications and worth of clinical application becasuse of its satisfactory results.

12.
Herald of Medicine ; (12): 779-784, 2014.
Article in Chinese | WPRIM | ID: wpr-452079

ABSTRACT

Objective To develop the ribavirin purity certified reference material( CRM ) which has measurement traceability and high accuracy,and establish an effective method of evaluation. Methods The homogeneity and the stability were checked by differential scanning calorimetry(DSC). High performance liquid chromatography(HPLC)and DSC methods were used for purity determination of ribavirin. Results Ribavirin showed satisfactory homogeneity and stability. The certified value of ribavirin was 99. 5%with an uncertainty of 0. 4%(k=2,P=0. 95). Conclusion Ribavirin purity CRM obtained in this paper has been proven to be a national primary CRM with high accuracy and traceability,which can be used to validate analytical methods,improve the accuracy of measurement data,establish meteorological traceability of analytical results as well as control the quality of ribavirin in the pharmaceutical industry.

13.
Journal of Medical Biomechanics ; (6): E447-E453, 2014.
Article in Chinese | WPRIM | ID: wpr-804349

ABSTRACT

Objective To explore the combined effects of mechanical stretch and interleukin-1β (IL-1β) on gene expression of extracellular matrix in rabbit corneal fibroblasts. Methods Isolated rabbit corneal fibroblasts were subjected to 15% equibiaxial stretch at frequency of 0.1 Hz for 12 h, 24 h and 36 h, respectively, in presence of IL-1β. The gene expressions of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases 1 (TIMP-1) and collagen type I alpha 1 (Collagen Iα1) were detected by real-time quantitative PCR. Results The mRNA levels of MMP-1, MMP-3 and MMP-9 could be up-regulated by IL-1β alone. However, MMP-1 and MMP-3 mRNA levels decreased with time, while MMP-9, TIMP-1 and collagen Iα1 increased with time. Compared with corresponding IL-1β treatment with mechanical stretch groups, the mRNA levels of MMP-1, MMP-3 and MMP-9 were increased and the mRNA levels of TIMP-1 and collagen Iα1 were decreased in a time-dependent manner. The mRNA level of Collagen Iα1 was decreased by loading mechanical stretch alone, and would further decrease time-dependently in combination with IL-1β treatment. Conclusions Mechanical stretch combined with IL-1β may facilitate the corneal tissue damage, thereby contribute to the development of keratectasia.

14.
Chinese Pharmaceutical Journal ; (24): 621-628, 2013.
Article in Chinese | WPRIM | ID: wpr-860413

ABSTRACT

OBJECTIVE: To establish the preparation method and detection technology of ribavirin polymorphism, and to estimate the bioavailability differences among the ribavirin polymorphs. METHODS: Through polymorphism screening, ribavirin crystals of the form A, B, C, D were obtained. The crystal forms of ribavirin were characterized by different analysis methods, such as single crystal X-ray diffraction method (SXRD), powder X-ray diffraction method (PXRD), differential scanning calorimetry method (DCS), infrared spectrum method (IR) and melting point method (MP). solid ribavirin in different forms were orally administered to rats, and an HPLC-MS method was established to determine the plasma levels of ribavirin, and the bioavailability was analyzed. RESULTS: Of the four polymorphs of ribavirin, form C and form D were reported for the first time. The four polymorphic forms all could be identified by PXRD, DSC, IR and MP. The ρmax and AUC0-t of form A were superior to those of the other forms. CONCLUSION: Characteristic data for ribavirin polymorphism are obtained; and form A of ribavirin is a suitable medicinal crystal. This study has provided the basis for choice of medicinal crystal and the improvement of quality standards.

15.
Journal of Medical Biomechanics ; (6): E245-E250, 2012.
Article in Chinese | WPRIM | ID: wpr-803972

ABSTRACT

As a new technique of determining the viscoelasticity of soft biomaterials and cell cytoplasm in living cells, particle tracking microrheology (PTM) is mainly applied in the biomechanical research field, such as cell movement, embryo development, laminopathies. PTM has many advantages over the conventional detection methods in cell mechanics. Using this technique, the Brownian motion of probe particles embedded in the medium could be measured by the video-microscopy, and the movement trajectories of the probe could be mathematically transformed into the mean squared displacements (MSDs) thus to extract the parameters such as the frequency-dependent viscoelastic modulus or the creep compliance from the time dependent MSDs of the probes. The basic principles of PTM technique and its application in biomechanics will be reviewed in this paper.

16.
Chinese Medical Journal ; (24): 401-407, 2011.
Article in English | WPRIM | ID: wpr-321494

ABSTRACT

<p><b>BACKGROUND</b>Mesenchymal stem cells (MSCs) transplantation may partially restore heart function in the treatment of acute myocardial infarction (AMI). The aim of this study was to explore the beneficial effects of MSCs modified with heme xygenase-1 (HO-1) on post-infarct swine hearts to determine whether the induction of therapeutic angiogenesis is modified by the angiogenic cytokines released from the implanted cells.</p><p><b>METHODS</b>In vitro, MSCs were divided into four groups: (1) non-transfected MSCs (MSCs group), (2) MSCs transfected with the pcDNA3.1-Lacz plasmid (Lacz-MSCs group), (3) MSCs transfected with pcDNA3.1-hHO-1 (HO-1-MSCs group), and (4) MSCs transfected with pcDNA3.1-hHO-1 and pretreatment with an HO inhibitor, tin protoporphyrin (SnPP) (HO-1-MSCs + SnPP group). Cells were cultured in an airtight incubation bottle for 24 hours, in which the oxygen concentration was maintained at < 1%, followed by 12 hours of reoxygenation. After hypoxia/reoxygen treatment, ELISA was used to measure transforming growth factor (TGF-β) and fibroblast growth factor (FGF-2) in the supernatant. In vivo, 28 Chinese mini-pigs were randomly allocated to the following treatment groups: (1) control group (saline), (2) Lacz-MSCs group, (3) HO-1-MSCs group, and (4) HO-1-MSCs + SnPP group. About 1 × 10(7) of autologous stem cells or an identical volume of saline was injected intracoronary into porcine hearts 1 hour after MI. Magnetic resonance imaging (MRI) assay and postmortem analysis were assessed four weeks after stem cell transplantation.</p><p><b>RESULTS</b>Post hypoxia/reoxygenation in vitro, TGF-β in the supernatant was significantly increased in the HO-1-MSCs ((874.88 ± 68.23) pg/ml) compared with Lacz-MSCs ((687.81 ± 57.64) pg/ml, P < 0.001). FGF-2 was also significantly increased in the HO-1-MSCs ((1106.48 ± 107.06) pg/ml) compared with the Lacz-MSCs ((853.85 ± 74.44) pg/ml, P < 0.001). In vivo, at four weeks after transplantation, HO-1 gene transfer increased the capillary density in the peri-infarct area compared with the Lacz-MSCs group (14.24 ± 1.66/HPFs vs. 11.51 ± 1.34/HPFs, P < 0.001). Arteriolar density was also significantly higher in HO-1-MSCs group than in the Lacz-MSCs group (7.86 ± 2.00/HPFs vs. 6.45 ± 1.74/HPFs, P = 0.001). At the same time, the cardiac function was significantly improved in the HO-1-MSCs group compared with the Lacz-MSCs group ((53.17 ± 3.55)% vs. (48.82 ± 2.98)%, P < 0.05). However, all these effects were significantly abrogated by SnPP.</p><p><b>CONCLUSION</b>MSCs provided a beneficial effect on cardiac function after ischemia/reperfusion by the induction of therapeutic angiogenesis, and this effect was amplified by HO-1 overexpression.</p>


Subject(s)
Animals , Blotting, Western , Cell Differentiation , Genetics , Physiology , Heme Oxygenase-1 , Genetics , Metabolism , Magnetic Resonance Imaging , Mesenchymal Stem Cells , Cell Biology , Metabolism , Myocardial Reperfusion Injury , Metabolism , Swine , Swine, Miniature
17.
Chinese Medical Journal ; (24): 1199-1204, 2011.
Article in English | WPRIM | ID: wpr-239867

ABSTRACT

<p><b>BACKGROUND</b>Superparamagnetic iron oxide (SPIO) particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging (MRI). Micrometer-sized superparamagnetic iron oxide (MPIO) particles and nanometer-sized ultrasmall superparamagnetic iron oxide (USPIO) are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction (AMI).</p><p><b>METHODS</b>An AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 10(7) magnetically labeled mesenchymal stem cells (MR-MSCs). The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.</p><p><b>RESULTS</b>MR-MSCs appeared as a local hypointense signal on T₂*-weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T₂*-weighted MRI, contrast to noise ratio (CNR) decreased in the MPIO-labeled group (16.07 ± 5.85 vs. 10.96 ± 1.34) and USPIO-labeled group (11.72 ± 1.27 vs. 10.03 ± 0.96) from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.</p><p><b>CONCLUSIONS</b>We demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability. USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.</p>


Subject(s)
Animals , Cell Survival , Contrast Media , Ferric Compounds , Magnetic Resonance Imaging , Methods , Male , Myocardial Infarction , Diagnosis , Pathology , Stem Cells , Cell Biology , Swine
18.
Chinese Journal of Cardiology ; (12): 692-695, 2009.
Article in Chinese | WPRIM | ID: wpr-236424

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of intracoronary transfer of autologous HO-1 overexpressed MSCs in porcine model of myocardial ischemia (1 h)/reperfusion.</p><p><b>METHODS</b>Apoptosis was assayed and cytokine concentrations in supernatant were measured in cells exposed to hypoxia-reoxygen in vitro. In vivo, Chinese male mini-pigs were allocated to the following treatment groups: control group (saline), MSCs group (MSCs), MSCs transfected with pcDNA3.1-nHO-1 (HO-1-MSCs). 1 x 10(7) of autologous stem cells or identical volume of saline was injected intracoronary into porcine hearts 1 h after ischemia. MRI assay and postmortem analysis were assessed 3 months after stem cell transplantation.</p><p><b>RESULTS</b>In vitro, cell apoptosis rate post hypoxia-reoxygen was significantly reduced in HO-1-MSCs group (30.30% +/- 7.64%) compared with that in MSCs group (56.93% +/- 4.68%, P < 0.001) and LacZ-MSCs group (55.88% +/- 4.38%, P < 0.001), VEGF was also significantly upregulated in HO-1-MSCs group [(768.44 +/- 78.38) pg/ml] compared with that in MSCs group [(555.27 +/- 67.67) pg/ml, P < 0.001] and LacZ-MSCs group [(522.97 +/- 71.45) pg/ml, P < 0.001]. In vivo, cardiac function was significantly improved in both MSCs transplantation groups compared to saline group (all P < 0.05 vs.saline) and the left ventricular ejection fraction was significantly higher in HO-1-MSCs group compared with that in MSCs group at 3 months after transplantation (53.50% +/- 2.09% vs. 49.54% +/- 2.74%, P = 0.017), capillary density in the peri-infarct area was also significantly higher in HO-1-MSC group than that in MSCs group [(14.59 +/- 2.39)/HPF vs. (11.78 +/- 2.48)/HPF, P = 0.033].</p><p><b>CONCLUSIONS</b>Efficacy of HO-1 overexpressed MSCs on improving cardiac function and promoting angiogenesis was greater than those by MSCs in this porcine ischemia/reperfusion model.</p>


Subject(s)
Animals , Apoptosis , Cells, Cultured , Genetic Vectors , Heme Oxygenase-1 , Genetics , Male , Mesenchymal Stem Cell Transplantation , Myocardial Infarction , Therapeutics , Myocardial Ischemia , Therapeutics , Swine , Swine, Miniature , Transfection
19.
Chinese Medical Journal ; (24): 544-550, 2008.
Article in English | WPRIM | ID: wpr-287695

ABSTRACT

<p><b>BACKGROUND</b>Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging.</p><p><b>METHODS</b>Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01).</p><p><b>RESULTS</b>A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (10(7) cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87+/-2.45)% vs (39.04+/-2.80)%, P>0.05), but significantly improved in the MR-MSCs group ((56.85+/-1.29)% vs (40.67+/-2.00)%, P<0.05) and unlabeled group ((55.38+/-1.07)% vs (41.78+/-2.08)%, P<0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group.</p><p><b>CONCLUSION</b>Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.</p>


Subject(s)
Animals , Blotting, Western , Cell Survival , Disease Models, Animal , Magnetic Resonance Imaging , Magnetics , Mesenchymal Stem Cell Transplantation , Myocardial Infarction , Therapeutics , Swine , Ventricular Function, Left
20.
Chinese Journal of Cardiology ; (12): 1004-1008, 2008.
Article in Chinese | WPRIM | ID: wpr-355844

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of magnetically labeled mononuclear stem cells (MR-MNC) and mesenchymal stem cells (MR-MSC) transplantation in a swine acute myocardial infarction (AMI) model by MR imaging.</p><p><b>METHODS</b>AMI model was established in swines by balloon occlusion of the left anterior descending coronary artery, 10(7) autologous MR-MSC (n = 7), MR-MNC (n = 6) or PBS (n = 6) were delivered via intracoronary infusion within 1 week after AMI [(4.8 +/- 1.3) days]. Changes of infarct size and cardiac function were assessed with the use of 3.0T MR scanner before AMI, at 1 and 8 weeks post AMI.</p><p><b>RESULTS</b>Magnetically labeled stem cells could be identified in the region of AMI by cardiac MR imaging. Eight weeks post transplantation, infarct size was significantly reduced in MR-MSC transplantation group (8.5% +/- 0.5% vs. 24.7% +/- 3.1%, P < 0.05) and in MR-MNC transplantation (12.3% +/- 1.5% vs. 26.1% +/- 1.5%, P < 0.05) while infarct size remained unchanged in PBS group (P > 0.05) compared to values at 1 week post AMI, left ventricular ejection fraction (LVEF) was also significantly higher in MR-MSC transplantation group (56.9% +/- 1.3% vs. 40.7% +/- 2.0%, P < 0.05) and MR-MNC transplantation group (52.8% +/- 1.4% vs. 41.9% +/- 3.3%, P < 0.05) compared to LVEF at 1 week post AMI. LVEF increase was more significant in swines received MR-MSC transplantation than MR-MNC transplantation (16.2% +/- 1.2% vs. 10.9% +/- 3.0%, P < 0.05). Prussian blue staining identified stem cells in corresponding myocardial regions with as by MRI. Western blot analysis demonstrated that cardiac expressions of myosin heavy chain (MHC) in MR-MSC group (100.3 +/- 5.5) and in MR-MNCs group (95.5 +/- 4.2) were significantly higher than that in PBS group (75.7 +/- 5.7, P < 0.05), myocardial troponin T (cTNT) expression in MR-MSC group (124.0 +/- 5.8) and MR-MNC group (118.4 +/- 4.4) were also significantly higher than in PBS group (93.3 +/- 3.9, P < 0.05) while MMP2/TIMP1 ratios in MR-MSC group (0.6 +/- 0.1) and MR-MNC group (0.6 +/- 0.1) were significantly lower than that in PBS group (4.2 +/- 0.2, P < 0.05).</p><p><b>CONCLUSIONS</b>Magnetically labeled MR-MSC and MR-MNC homed to heart post myocardial infarction and reduced infarct size, improved cardiac function. MR-MSC is superior to MR-MNC on improving cardiac function.</p>


Subject(s)
Animals , Disease Models, Animal , Magnetic Resonance Imaging , Male , Mesenchymal Stem Cell Transplantation , Myocardial Infarction , Therapeutics , Swine , Swine, Miniature , Treatment Outcome
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