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1.
China Journal of Chinese Materia Medica ; (24): 2174-2179, 2015.
Article in Chinese | WPRIM | ID: wpr-337964

ABSTRACT

There have been very few studies on the effect of Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction in inhibiting apoptosis in myocardial ischemial injury caused by coronary heart disease. In this experiment, Gualou Xiebai Banxia decoction combined with-Xuefu Zhuyu decoction were used to intervene the miniature swine phlegm and blood stasis type coronary heart disease model, in order to observe the effect of the combined prescription on the myocardial apoptosis and the expressions of Bcl-2, Bax, Caspase-3, Caspase-9 in the model. Totally 15 Chinese experimental miniature swine were adopted and randomly divided into the control group, the model group and the phlegm and stasis-treating group. The model group and the stasis-treating group were fed with high fat diets for two weeks, intervened with the coronary artery injury and then given drugs and high fat diets for eight weeks. The control group was fed with ordinary diets for 10 weeks, without the coronary artery injury. After the experiment, myocardia at the juncture of infracted areas were collected and made into formalin-fixed paraffin sections. The TDT-mediate dUTP nick end labeling (TUNEL) assay was used to detect the myocardial apoptosis. The immunohistochemistry (IHC) technique was applied to detect Bcl-2, Bax, Caspase-3, Caspase-9 levels in myocardial tissues. According to the findings, the apoptosis indexes (AI) for the control group, the model group and the phlegm and stasis-treating group were 0.92%, 27.68%, 17.28%, respectively. The AI of the phlegm and stasis-treating group was significantly lower than that of the model group (P < 0.01). Compared with the model group, the phlegm and stasis-treating group showed significantly higher Bcl-2 protein expression (P < 0.01) and lower Bax, Caspase-3 and Caspase-9 protein expressions (P < 0.01). In conclusion, Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction have a significant protective effect against the myocardial apoptosis in miniature swine phlegm and blood stasis type coronary heart disease model.


Subject(s)
Animals , Female , Male , Apoptosis , Caspases , Metabolism , Coronary Disease , Drug Therapy , Disease Models, Animal , Drug Therapy, Combination , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Myocardium , Pathology , Phytotherapy , Proto-Oncogene Proteins c-bcl-2 , Swine , Swine, Miniature , bcl-2-Associated X Protein
2.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 482-490, 2014.
Article in English | WPRIM | ID: wpr-351052

ABSTRACT

Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery (BA) of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows: (1) The diameters of BA and middle cerebral artery (MCA) were 314.5±15.7 μm (n=15) and 233.3±10.1 μm (n=12) at 10 mmHg working pressure (P<0.05), respectively. Pressure-induced vasomotion occurred in BA (22/28, 78.6%), but not in MCA (4/31, 12.9%) from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; (2) The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic contractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7±4.7 (n=13) per 10 min at 60 mmHg working pressure; (3) The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 18β-GA, TEA or in Ca(2+)-free medium. Nifedipine, NFA, 18β-GA or Ca(2+)-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results suggest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca(2+)-activated Cl(-) channels (CaCCs) currents and K(Ca) currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells (VSMCs) to activate CaCCs. Depolarization in turn activates voltage-dependent Ca(2+) channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calcium-induced calcium release from ryanodine-sensitive stores activates K(Ca) channels and hyperpolarizes VSMCs, which provides a negative feedback loop for regenerating the contractile cycle.


Subject(s)
Animals , Female , Male , Rats , Basilar Artery , Cell Biology , Metabolism , Physiology , Chloride Channels , Metabolism , Membrane Potentials , Physiology , Muscle, Smooth, Vascular , Cell Biology , Metabolism , Myocytes, Smooth Muscle , Cell Biology , Metabolism , Potassium Channels, Calcium-Activated , Metabolism , Rats, Wistar , Vasoconstriction , Physiology , Vasodilation , Physiology
3.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 482-90, 2014.
Article in English | WPRIM | ID: wpr-636711

ABSTRACT

Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery (BA) of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows: (1) The diameters of BA and middle cerebral artery (MCA) were 314.5±15.7 μm (n=15) and 233.3±10.1 μm (n=12) at 10 mmHg working pressure (P<0.05), respectively. Pressure-induced vasomotion occurred in BA (22/28, 78.6%), but not in MCA (4/31, 12.9%) from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; (2) The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic contractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7±4.7 (n=13) per 10 min at 60 mmHg working pressure; (3) The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 18β-GA, TEA or in Ca(2+)-free medium. Nifedipine, NFA, 18β-GA or Ca(2+)-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results suggest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca(2+)-activated Cl(-) channels (CaCCs) currents and K(Ca) currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells (VSMCs) to activate CaCCs. Depolarization in turn activates voltage-dependent Ca(2+) channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calcium-induced calcium release from ryanodine-sensitive stores activates K(Ca) channels and hyperpolarizes VSMCs, which provides a negative feedback loop for regenerating the contractile cycle.

4.
Chinese Journal of Applied Physiology ; (6): 25-28, 2013.
Article in Chinese | WPRIM | ID: wpr-358688

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the difference in membrane current of vascular smooth muscle cells (VSMCs) in brain artery (BA) of spontaneously hypertensive rats (SHR) and Wistar rats.</p><p><b>METHODS</b>We compared the properties of spontaneous transient outward K+ currents (STOCs), the density and composition of current of VSMCs in BA of SHR and Wistar rats by whole-cell patch clamp technique.</p><p><b>RESULTS</b>(1) When the command voltage was 0, + 20, + 40 and + 60 mV respectively, the current densities of VSMCs in BA of SHR and Wistar rats were significant different (P < 0.01). (2) The whole-cell current of VSMCs was partly inhibited by 1 mmol/L4-AP (voltage-gated K+ channel blocker) or 1 mmol/L TEA (big conductance Ca(2+)-activated K+ channel blocker) respectively. (3) The frequency and amplitude of STOCs in SHR were faster and bigger than those in Wistar rats. 1 mmol/L TEA almostly inhibited the STOCs, but not by 4-AP.</p><p><b>CONCLUSION</b>These results suggest that the current densities of VSMCs in BA of SHR and Wistar rats are significant different, the outward current of VSMCs in BA of SHR and Wistar rats are composed by Kv and BK(Ca). SHR express more STOCs mediated by BK(Ca), than Wistar rats.</p>


Subject(s)
Animals , Rats , Cerebral Arteries , Cell Biology , Physiology , Membrane Potentials , Physiology , Muscle, Smooth, Vascular , Cell Biology , Physiology , Myocytes, Smooth Muscle , Physiology , Patch-Clamp Techniques , Potassium Channels, Calcium-Activated , Physiology , Potassium Channels, Voltage-Gated , Physiology , Rats, Inbred SHR , Rats, Wistar
5.
Chinese journal of integrative medicine ; (12): 771-776, 2013.
Article in English | WPRIM | ID: wpr-267206

ABSTRACT

<p><b>OBJECTIVE</b>To examine the effect of the zedoary essential component-eluting stent (ZES) on a porcine coronary neointimal formation.</p><p><b>METHODS</b>ZES, sirolimus-eluting stents (SES), and bare metal stents (BMS) were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperplasia effects.</p><p><b>RESULTS</b>ZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES (P<0.05). Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69 ± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups (both were 3.00 ± 0.00 at either 30 or 90 days, P<0.05). Well developed endothelium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group.</p><p><b>CONCLUSION</b>The ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.</p>


Subject(s)
Animals , Coated Materials, Biocompatible , Pharmacology , Coronary Stenosis , Pathology , Coronary Vessels , Pathology , Curcuma , Chemistry , Endothelium, Vascular , Pathology , Inflammation , Pathology , Microscopy, Electron, Scanning , Neointima , Pathology , Prosthesis Implantation , Stents , Sus scrofa , Time Factors
6.
Chinese journal of integrative medicine ; (12): 582-588, 2013.
Article in English | WPRIM | ID: wpr-293333

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects and mechanisms of hawthorn leaves flavonoids (HLF) on acute myocardial ischemia/reperfusion in anesthetized dogs.</p><p><b>METHODS</b>The acute ischemia models were prepared by ligating left anterior descending (LAD) artery for 60 min. Qualified 15 male dogs were randomly divided into 3 groups with 5 in each group: blank control (treated with normal saline 3 mL/kg) group, HLF low dosage (5 mg/kg) group and high dosage (10 mg/kg) group, with an once injection through a femoral vein 5 min before reperfusion. Epicardial electrocardiogram was adopted to measure the scope and degree of myocardial ischemia. Simultaneously, neutrophil infiltration in infarct (Inf) and remote site (RS) of myocardial tissue was measured by myeloperoxidase (MPO) activity assay. The serum interleukin-1 (IL-1) and tumor necrosis factorα (TNF-α) content were quantified by radioimmuno-assay. Furthermore, expression of G protein-coupled receptor kinase 2 (GRK2) and nuclear factor κB (NF-κB) in Inf and RS tissue were detected by Western blotting technique.</p><p><b>RESULTS</b>Ischemia and reperfusion increased the MPO activity and IL-1 and TNF-α content. HLF (10 and 5 mg/kg) could significantly decrease the degree and scope of myocardial ischemia; markedly inhibit the increase of MPO activity, and IL-1 and TNF-α content induced by myocardial ischemia/infarction. Furthermore, HLF increased GRK2 expression and inhibited NF-κB expression in Inf tissue.</p><p><b>CONCLUSION</b>HLF could improve the situation of acute myocardial ischemia and inhibit the inflammation in anesthetized dogs, which might be due to its increasing effect on the GRK2 and NF-κB expressions.</p>


Subject(s)
Animals , Dogs , Male , Anesthesia , Crataegus , Chemistry , Drug Evaluation, Preclinical , Flavonoids , Pharmacology , Therapeutic Uses , Inflammation , Myocardial Ischemia , Drug Therapy , Pathology , Myocardial Reperfusion Injury , Drug Therapy , Neutrophil Infiltration , Plant Extracts , Pharmacology , Therapeutic Uses , Plant Leaves , Chemistry , Random Allocation
7.
Chinese Journal of Applied Physiology ; (6): 128-132, 2012.
Article in Chinese | WPRIM | ID: wpr-329928

ABSTRACT

<p><b>OBJECTIVE</b>A variety of inner ear disease is related to microcirculation disturbance of inner ear, but smooth muscle cells (SMC) and endothelial cells (EC) of the spiral modiolar artery (SMA), which is the main blood supply to the inner ear, physiological feature is not very clear.</p><p><b>METHODS</b>In this study, two-intracellular microelectrode recording technique and cell staining techniques to study the SMC and EC resting membrane potential characteristics and communication links between cells of SMA.</p><p><b>RESULTS</b>Study found that SMC and EC have high and low resting membrane potential state, two state of the resting membrane potential of cells to ACh and high K+ response is completely different. The different types of cells, EC-EC, SMC-SMC and SMC-EC, can simultaneously record by two-microelectrode, two cell resting membrane potential can also be a double-high RP, double-low RP and one high- and one low- RP. Experiment recorded in one high- and one low- RP are the SMC-EC types, and ECs initial membrane potential are high potential, SMCs membrane potential are low initial potential. The double-high and double-low RP can be SMC-SMC or EC-EC or SMC-EC types.</p><p><b>CONCLUSION</b>The results show that SMC and EC in the 0.3 - 0.5 mm range, similar type of cells have very good communication, can function together to maintain good and consistent, heterogeneous cell performance is more different.</p>


Subject(s)
Animals , Arteries , Cell Biology , Cochlea , Physiology , Endothelial Cells , Physiology , Guinea Pigs , Membrane Potentials , Physiology , Myocytes, Smooth Muscle , Physiology
8.
Acta Physiologica Sinica ; (6): 533-539, 2011.
Article in Chinese | WPRIM | ID: wpr-335958

ABSTRACT

The aim of the present study was to investigate the effects of acute hypoxia on the electrophysiological properties of vascular smooth muscle cells (VSMCs) in arteriole. Guinea-pig anterior inferior cerebellar artery (AICA) segments were isolated, and outer layer connective tissue was removed by collagenase A digestion and microforceps. By perfusion with physical saline solution containing no glucose and low oxygen, VSMC model of acute hypoxia was established. The model was studied by whole-cell patch clamp recording technique. Results were shown as below: (1) Acute hypoxia induced an outward current with amplitude of (36.4 ± 9.2) pA at holding potential of -40 mV, and the rest potential (RP) of the VSMCs was hyperpolarized from (-33.2 ± 1.9) mV to (-38.4 ± 1.5) mV. Acute hypoxia increased the outward current of VSMCs in a voltage-dependent manner, this enhancing effect being more pronounced at potentials ranging from 0 to +40 mV. The whole-cell membrane current of VSMCs induced by step command (+40 mV) increased from (650 ± 113) pA to (1 900 ± 197) pA. In the presence of 1 mmol/L tetraethylammonium (TEA), the enhancement of the VSMC membrane current by acute hypoxia was significantly reduced. (2) Acute hypoxia increased the membrane resistance (R(input)) of the VSMCs in AICA from (234 ± 63) MΩ to (1 211 ± 201) MΩ, and decreased the membrane capacitance (C(input)) from (279.3 ± 83.2) pF to (25.4 ± 1.9) pF. In the presence of 30 μmol/L 18β-glycyrrhetinic acid (18βGA) and 10 mmol/L TEA, the effects of acute hypoxia on the membrane current of VSMCs were nearly abolished. These results suggest that acute hypoxia causes vascular hyperpolarization and vasodilation, possibly by activating big conductance Ca(2+)-activated K(+) channels (BK(Ca)) of the VSMCs, and inhibits gap junctions between VSMCs, thus improving microcirculation and localizing the hypoxia-induced damage.


Subject(s)
Animals , Female , Male , Arteries , Cerebellum , Gap Junctions , Metabolism , Physiology , Guinea Pigs , Hypoxia , In Vitro Techniques , Muscle, Smooth, Vascular , Cell Biology , Metabolism , Physiology , Myocytes, Smooth Muscle , Metabolism , Physiology , Patch-Clamp Techniques , Potassium Channels , Physiology
9.
Acta Physiologica Sinica ; (6): 549-554, 2011.
Article in Chinese | WPRIM | ID: wpr-335956

ABSTRACT

The aim of the present study was to investigate the effect of 18β-glycyrrhetinic acid (18βGA) on the membrane current of vascular smooth muscle cells (VSMCs) in arteriole. Guinea pig anterior inferior cerebellar artery (AICA) and mesenteric artery (MA) were isolated, and single VSMCs were harvested using digestion with papain and collagenase IA. Outward currents of the VSMCs were recorded by whole-cell patch clamp technique. Results were shown as below: (1) 1 mmol/L 4-AP and 1 mmol/L TEA both could partially inhibit the whole-cell current of VSMCs in arterioles. (2) 18βGA inhibited the outward current of VSMCs in a concentration-dependent manner. The inhibitory rates of 10, 30 and 100 μmol/L 18βGA on the membrane current of VSMCs (+40 mV) were (25.3 ± 7.1)%, (43.1 ± 10.4)% and (68.4 ± 3.9)% respectively in AICA, and (13.2 ± 5.6)%, (34.2 ± 4.0)% and (59.3 ± 7.3)% respectively in MA. There was no significant difference between the inhibitory effects of 18βGA on AICA and MA. 18βGA also inhibited the outward current of VSMCs in a voltage-dependent manner. 18βGA induced a more pronounced inhibition of the outward current from 0 to +40 mV, especially at +40 mV. (3) With the pretreatment of 10 mmol/L TEA, the inhibitory effect of 18βGA on the membrane current of VSMCs was significantly abolished. These results suggest that the outward current of VSMCs in arterioles is mediated by voltage-dependent K(+) channels (K(v)) and big conductance calcium-activated K(+) channels (BK(Ca)), which can be inhibited by 18βGA in concentration- and voltage-dependent way.


Subject(s)
Animals , Female , Male , Arterioles , Physiology , Cerebellum , Gap Junctions , Physiology , Glycyrrhetinic Acid , Pharmacology , Guinea Pigs , In Vitro Techniques , Membrane Potentials , Mesenteric Arteries , Cell Biology , Physiology , Muscle, Smooth, Vascular , Cell Biology , Physiology , Myocytes, Smooth Muscle , Physiology , Patch-Clamp Techniques , Potassium Channels, Calcium-Activated , Physiology , Potassium Channels, Voltage-Gated , Physiology
10.
Chinese Journal of Applied Physiology ; (6): 140-143, 2011.
Article in Chinese | WPRIM | ID: wpr-301481

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the distribution and mechanism of coronary arteriole (CA) cell resting membrane potential (RP) in guinea pigs.</p><p><b>METHODS</b>Cell RP was recorded by intracellular microelectrode in isolated guinea pig coronary arteriole (diameter < 100 microm).</p><p><b>RESULTS</b>(1) Experiments were carried out in 112 cells with a mean RP of (-65 +/- 4.2)mV, the distribution of coronary arteriole cell RP fitted by Gaussian function was bimodal, one peak was -43 mV termed high RP, the other was -74 mV termed low RP. 10 mmol/L K+ and 3 micromol/ L acetylcholine(ACh) induced hyperpolarization in high-RP cells with (-7.4 +/- 0.87) mV (n = 13) and (-15 +/- 1.24) mV (n = 16) respectively, and induced depolarization in low-RP cells with (9.6 +/- 1.2) mV (n = 23) and (8.7 +/- 0.69) mV (n = 15) respectively. (2) The inward rectifier K+ channel (K(ir)) blocker Ba2+ caused concentration-dependent depolarization in low-RP cells with an EC50 of 120 micromol/L 100 micromol/L Ba2+ or higher could shift low-RP cells to high-RP state, the response of these cells to high K+ and ACh became a hyperpolarization.</p><p><b>CONCLUSION</b>The distribution of coronary vascular cell RP is bimodal, high K+ and ACh induce different responses in low and high RP cells. The two RP states are exchangeable mainly due to all-or-none conductance changes of K(ir).</p>


Subject(s)
Animals , Female , Male , Acetylcholine , Metabolism , Arterioles , Cell Biology , Coronary Vessels , Cell Biology , Physiology , Guinea Pigs , Membrane Potentials , Physiology , Microelectrodes , Myocardium , Metabolism , Potassium Channels, Inwardly Rectifying , Physiology
11.
Acta Physiologica Sinica ; (6): 421-426, 2010.
Article in Chinese | WPRIM | ID: wpr-337731

ABSTRACT

Arterioles are major contributors to the control of systemic blood pressure and local blood flow. In this study, we compared electrophysiological properties of vascular smooth muscle cells (VSMCs) in anterior inferior cerebellar artery (AICA), mesenteric artery (MA) and spiral modiolar artery (SMA) by intracellular microelectrode recording and whole-cell patch clamp recording techniques. Results were shown as below: (1) Intracellular microelectrode recordings were made from VSMCs in AICA, MA and SMA with resting potentials of (-68±1.8) (n=65), (-71±2.4) (n=80) and (-66±2.9) mV (n=58), respectively. There was no significant difference in resting potentials among arterioles. (2) The membrane capacitance and membrane conductance in situ cells were much larger than those in dispersed smooth muscle cells by whole-cell recording techniques, and there was significant difference among arterioles, which were in the order: MA>AICA>SMA. After application of gap junction blocker 2-APB (100 μmol/L), the membrane capacitance and membrane conductance in situ cells were very close with those in single smooth muscle cells. (3) The I/V relation of whole-cell current of dissociated smooth muscle cells (AICA, MA and SMA) showed a prominent outward rectification, and the currents were substantially inhibited by 1 mmol/L 4-AP or 10 mmol/L TEA. When the command voltage was +40 mV, the current densities of VSMCs in AICA, MA and SMA were (26±2.0), (24±1.7) and (18±1.3) pA/pF respectively. SMA showed significant difference in the current density from AICA and MA respectively. These results suggest that the electrophysiological properties of coupling strength of gap junction and current density of smooth muscle cells are different among arterioles in the guinea pig.


Subject(s)
Animals , Female , Male , Arterioles , Cell Biology , Physiology , Cerebellum , Cochlea , Electrophysiological Phenomena , Guinea Pigs , Mesenteric Arteries , Cell Biology , Muscle, Smooth, Vascular , Cell Biology , Physiology
12.
Chinese journal of integrative medicine ; (12): 145-150, 2010.
Article in English | WPRIM | ID: wpr-344934

ABSTRACT

<p><b>OBJECTIVE</b>To study the effects of the Weinaokang (WNK), the active compounds extracted from Ginkgo, Ginseng, and saffron, on ischemia/reperfusion (I/R)-induced vascular injury to cerebral microvessels after global cerebral ischemia.</p><p><b>METHODS</b>Male C57BL/6J mice were randomly divided into 5 groups (10 animals/group): the sham group (0.5% CMC-Na, 20 mL/kg), the I/R model group (0.5% CMCNa, 20 mL/kg), the I/R+Crocin control group (20 mg/kg), the I/R+high dose WNK group (20 mg/kg), and the I/R+low dose WNK group (10 mg/kg). Bilateral common carotid artery occlusion (BCCAO, 20 min) in mice, followed by 24 h reperfusion, was built. The generation of nitric oxide (NO), the activity of nitric oxide synthase (NOS), the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), and the expression of matrix metalloproteinases-9 (MMP-9) and G protein-coupled receptor kinase 2 (GRK2) in cortical microvascular homogenates were evaluated. The ultrastructural morphology of cortical microvascular endothelial cells (CMEC) was observed.</p><p><b>RESULTS</b>The transient global cerebral ischemia (20 min), followed by 24 h of reperfusion, significantly promoted the generation of NO and the activity of NOS. The reperfusion led to serious edema with mitochondrial injuries in the cortical CMEC, as well as enhanced membrane GRK2 expression and reduced cytosol GRK2 expression. Furthermore, enhanced phosphorylation of ERK1/2 and decreased expression of MMP-9 were detected in cortical microvessels after I/R (20 min/24 h). As well as the positive control Crocin (20 mg/kg, 21days), pre-treatment with WNK (20, 10 mg/kg, 21 days) markedly inhibited nitrative injury and modulated the ultrastructure of CMEC. Furthermore, WNK inhibited GRK2 translocation from cytosol to the membrane (at 20 mg/kg) and reduced ERK1/2 phosphorylation and MMP-9 expression in cortical microvessels.</p><p><b>CONCLUSION</b>WNK and its active compounds (Crocin) are effective to suppress I/R-induced vascular injury to cerebral microvessels after global cerebral ischemia with the target on GRK2 pathways.</p>


Subject(s)
Animals , Male , Mice , Brain Ischemia , Drug Therapy , Metabolism , Cerebral Cortex , Metabolism , Drug Evaluation, Preclinical , Drugs, Chinese Herbal , Pharmacology , Extracellular Signal-Regulated MAP Kinases , Metabolism , G-Protein-Coupled Receptor Kinase 2 , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Mice, Inbred C57BL , Microvessels , Metabolism , Pathology , Nitric Oxide , Metabolism , Nitric Oxide Synthase , Metabolism , Phosphorylation , Reperfusion Injury , Drug Therapy , Metabolism , Signal Transduction , Tissue Distribution
13.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 228-232, 2009.
Article in Chinese | WPRIM | ID: wpr-273701

ABSTRACT

<p><b>OBJECTIVE</b>To establish a disease-syndrome conjugated animal model, the mini-swine coronary heart disease (CHD) model of phlegm-stasis cementation syndrome type, by high fat diet feeding and coronary artery balloon injury.</p><p><b>METHODS</b>Mini-swine were randomly divided into the control group and the model group, 6 in each group. They were fed with common forage and high fat forage respectively for 10 weeks and the coronary left anterior descending branch in the model group was injured by balloon intervention technique after 2-week feeding to establish CHD model. The model establishment and its physiopathological indices were evaluated by examinations on body mass index (BMI), blood levels of lipid, high-sensitivity C-reactive protein (hs-CRP), body surface electrocardiograph (BS-ECG), coronary angiography and pathological indices.</p><p><b>RESULTS</b>BMI, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), hs-CRP, sigma-ST and N-ST indicated by BS-ECG in the model group were all higher than those in the control group respectively (P < 0.05 or P < 0.01). Coronary angiography showed coronary lumen narrowed with apparent lumen loss, showing a significant difference as compared with the control group (P < 0.01). In EVG staining, the diameters of lumen in the model group was obviously narrow with intima proliferation, also significantly different to those in the control group (P < 0.01).</p><p><b>CONCLUSION</b>Disease-syndrome combined model for coronary heart disease of phlegm-stasis cementation syndrome type in mini-swine could be established by high fat diet feeding with coronary arterial injury.</p>


Subject(s)
Animals , Female , Male , Coronary Disease , Diagnosis, Differential , Dietary Fats , Disease Models, Animal , Medicine, Chinese Traditional , Methods , Random Allocation , Swine , Swine, Miniature , Syndrome
14.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 716-720, 2008.
Article in Chinese | WPRIM | ID: wpr-360589

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect and molecular mechanism of two haw leaf extracts, Vitexin-rhamnoside (VR) and Vitexin-glucoside (VG), and their preparation, Aoshaen injection (AI), on the polymorphonuclear leucocyte (PMN) adhesion during human umbilical vein endothelial cell (HUVEC) anoxia/reoxygenation (A/R) injury.</p><p><b>METHODS</b>The cell model of A/R injury duplicated by breaking off the oxygen supplying of HUVEC for 60 min followed with reoxygenating for 30 min (phase 1) or 240 min (phase 2) was taken as the experimental objective. The effects of testing drugs (VR, VG and AI) on PMN adhesion in the model cells were measured by enzyme immunoassay, and their effects on PMN superficial adhesion molecule CD11/CD18 expression were measured by flow cytometer respectively.</p><p><b>RESULTS</b>After 60 min of anoxia, HUVEC was shrunk and deformed. The adhesion between PMN and HUVEC significantly revealed at phase 1 in the model group, but it was fewer in the normal cell group, and also lesser in the groups treated with various drugs. The condition of cell adhesion revealed at phase 2 was the similar to that at phase 1. All testing drugs, VR, VG and AI, showed inhibitory effect on the cell adhesion at either phase 1 or phase 2, showing a certain dose-effect relationship. The expression of CD11/ CD18 was also inhibited by the testing drugs, and a good dose-effect relation was shown by VG and AI.</p><p><b>CONCLUSION</b>At the resting condition, there are almost no expression of CD11/CD18 molecule, but it could be enhanced by incubating PMN with supernate of A/R injured HUVEC culture, and more marked at phase 1. Adding the test drugs into the supernate could inhibit the enhancing of CD11/CD18 molecule expression and reduce the PMN-HUVEC adhesion, which may be one of the molecular mechanisms of haw leaf extracts and their preparation in protecting heart against A/R injury.</p>


Subject(s)
Female , Humans , Pregnancy , Cell Adhesion , Cell Hypoxia , Cells, Cultured , Crataegus , Chemistry , Hypoxia , Drug Therapy , Neutrophils , Physiology , Oxygen , Metabolism , Plant Extracts , Pharmacology , Plant Leaves , Chemistry , Umbilical Veins , Cell Biology
15.
China Journal of Chinese Materia Medica ; (24): 1772-1776, 2008.
Article in Chinese | WPRIM | ID: wpr-252228

ABSTRACT

On the base of reviewing the current literatures concerning the animal models with syndromes of Chinese medicine and investigating thee present state of the syndrome models, the authors have put forward a definition that research of animal models with the syndromes of Chinese medicine should be combined with clinical methods, and commented the potential application. Further it was suggested that clinical methods should be used in the exploration of scientific principles and the progresses on syndromes of Chinese medicine. In addition, intervene and evaluation of Chinese herbal medicine in animal model with integrated diseases and syndromes should be emphasized to establish a platform with special properties of TCM.


Subject(s)
Animals , Disease Models, Animal , Medicine, Chinese Traditional , Methods , Syndrome
16.
Chinese journal of integrative medicine ; (12): 206-210, 2007.
Article in English | WPRIM | ID: wpr-282409

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of Corocalm (shuguan capsule) on acute myocardial ischemia in anesthetized dogs and its possible therapeutic mechanism.</p><p><b>METHODS</b>The acute ischemia model was established by ligating the left anterior descending (LAD) artery. Twenty-five dogs were randomly divided into 5 groups (5 dogs in each group): the control group (treated with normal saline 3 mL/kg), the refined Guanxin Capsule group (GXC 200 mg/kg), high and low dose Corocalm groups (48.5 mg/kg for low dose group and 194.0 mg/kg for high dose group) and the Diltiazem group (5 mg/kg). The animals were treated via a single duodenal administration after the model was established. The experiments used epicardial electrocardiogram (EECG) to measure the scope and degree of myocardial ischemia. Simultaneously, the coronary blood flow (CBF) and serum activity levels of creatine phosphokinase (CK) and lactate dehydrogenase (LDH) were measured by electromagnetic flow meter and automatic biochemical analyzer respectively. The plasma endothelin (ET) content was quantified by radioimmunoassay.</p><p><b>RESULTS</b>Corocalm (48.5 mg/kg and 194.0 mg/kg) significantly decreased the degree and scope of myocardial ischemia, reduced the infarct area, markedly increased the CBF, and inhibited the increase of CK and LDH activities and ET levels induced by myocardial ischemia/infarction.</p><p><b>CONCLUSION</b>Corocalm could improve the state of acute myocardial ischemia and infarction in dogs. The mechanism of action might be correlated to increasing CBF, inhibiting CK and LDH activities and preventing ET release.</p>


Subject(s)
Animals , Dogs , Female , Male , Anesthesia , Capsules , Coronary Circulation , Creatine Kinase , Blood , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Endothelins , Blood , L-Lactate Dehydrogenase , Blood , Myocardial Ischemia , Drug Therapy , Pathology
17.
China Journal of Chinese Materia Medica ; (24): 1695-1699, 2007.
Article in Chinese | WPRIM | ID: wpr-287862

ABSTRACT

<p><b>OBJECTIVE</b>To study the therapeutical effects of Shuangshen Ningxin capsule on miniature swine after myocardial ischemia by intervention.</p><p><b>METHOD</b>Myocardial ischemic model miniature swine induced by self-thrombus via cardiac catheter in left anteriar descending coronary artery (LAD), were administrated Shuangshen Ningxin capsule for 6 days. The changes of coronary arteriography, hemodynamics, biochemistry and pathohistology were observed.</p><p><b>RESULT</b>6 days after modeling, LAD in myocardial ischemic miniature swine was basically embolized, cardiac output (CO), cardiac index (CI), left cardiac work (LCW) and left cardiac work index (LCWI) obviously lowed, and pathohistological analysis revealed myocardial degeneration, necrosis, fibrosis and inflammatory cell infiltration. After being administered with shuangshen Ningxin capsule 6 days, the degree of self-thrombus blocked LAD reduced, hemodynamic indexes of CO, CI, LCW, LCWI and blood plasm superoxide dismutase (SOD) activity increased, and systemic vascular resistance (SVR), systemic vascular resistance index (SVRI) and malondialdehyde (MDA) content were lowed. on the same time, pathohistological degeneration and necrosis reduced.</p><p><b>CONCLUSION</b>Shuangshen Ningxin capsule has anti-myocardial ischemia effect by improving cardiac muscle systolic function, increasing left cardiac work, inhibiting cardiac muscle cellular membrane lipid peroxidation.</p>


Subject(s)
Animals , Female , Male , Capsules , Cardiac Output , Cardiotonic Agents , Pharmacology , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Hemodynamics , Malondialdehyde , Blood , Myocardial Contraction , Myocardial Ischemia , Blood , Myocardium , Pathology , Panax , Chemistry , Plants, Medicinal , Chemistry , Salvia miltiorrhiza , Chemistry , Superoxide Dismutase , Blood , Swine , Swine, Miniature , Vascular Resistance
18.
China Journal of Chinese Materia Medica ; (24): 62-65, 2006.
Article in Chinese | WPRIM | ID: wpr-351005

ABSTRACT

<p><b>OBJECTIVE</b>To study the protective effects of saponines of stem and leaf of Panax notoginseng (PNSSL) on acute myocardial ischemia in anaesthetic dogs.</p><p><b>METHOD</b>The acute ischemia models were made by ligation of left anterior descending (LAD) artery. The myocardial blood flow (MBF) was determined by ultrasonic doppler. The experiments adopted epicardiogram mapping to measure the scope and degree of myocardial ischemia, quantitative histologic assay (nitroblue tetrazolium, N-BT stain) to determine the size of myocardial infarction. And the endothelin (ET) and thromboxane B2 (TXB2) were measured by radioimmunological assay.</p><p><b>RESULT</b>PNSSL was showed to obviously alleviate the degree of myocardial ischemia (sigma-ST) and narrow the ischemic area indicated by N-BT staining. In addition, PNSSL could increase the MBF of ischemia section. And the treatment could inhibit the ET and TXB2 release induced by ischemia and infarction.</p><p><b>CONCLUSION</b>PNSSL demonstrated to attenuate the damage subjected to myocardial ischemia and infarction, which may be due to its function of inhibiting the ET and TXA2 release, increasing the MBF, and then improving the damaged cardiac function.</p>


Subject(s)
Animals , Dogs , Female , Male , Coronary Circulation , Endothelins , Blood , Ginsenosides , Pharmacology , Myocardial Infarction , Drug Therapy , Panax , Chemistry , Plant Leaves , Chemistry , Plant Stems , Chemistry , Plants, Medicinal , Chemistry , Protective Agents , Pharmacology , Random Allocation , Thromboxane B2 , Blood
19.
Chinese journal of integrative medicine ; (12): 199-202, 2006.
Article in English | WPRIM | ID: wpr-314059

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the cardio-protective effects of Corocalm on acute myocardial ischemia in rats, and to explore its possible therapeutic mechanisms.</p><p><b>METHODS</b>The acute ischemic model was prepared by ligating the left anterior descending (LAD) coronary artery in rats. The animals were divided into 6 groups, 8 in each group. The sham operated group underwent heart exposure without ligation and were treated with normal saline 3 ml/kg, while the other 5 groups, the model groups, consisted of acceptable acute ischemic model rats and were also treated with normal saline, with the Guanxin Capsule (GXC) group treated with refined GXC, 600 mg/kg, the low and high dose Corocalm groups treated with 85 mg/kg and 340 mg/kg of Corocalm respectively, and the Diltiazem group, treated with Diltiazem 5 mg/kg, with all the tested drugs prepared with normal saline into equal volume (3 ml/kg) and administrated once via duodenum 10 min before ligation. Myocardial infarction area was determined by the quantitative histological assay with nitroblue tetrazolium (N-BT) stain. And the levels of creatine phosphokinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) content, and the activity of superoxide dismutase (SOD) in serum were measured by biochemical assay and spectrophotometry respectively. Besides, the blood viscosity in another 50 rats was determined, who received for 7 successive days oral administration with different concentration of Corocalm or aspirin.</p><p><b>RESULTS</b>It showed that low and high dose Corocalm could significantly reduce the infarction area, inhibit the increase of serum CK, LDH activity and MDA content, and enhance the SOD activity after ischemia/reperfusion. The whole blood viscosity at different shear rates in rats treated with high dose Corocalm was significantly lower than those treated with normal saline (P < 0.05).</p><p><b>CONCLUSION</b>Corocalm has favourable protective effects on heart in ischemic condition, the effect of which might be through its actions in inhibiting CK and LDH activity, scavenging oxygen free radicals, and lowering blood viscosity.</p>


Subject(s)
Animals , Male , Rats , Acute Disease , Blood Viscosity , Cardiotonic Agents , Pharmacology , Creatine Kinase , Blood , Drugs, Chinese Herbal , Pharmacology , L-Lactate Dehydrogenase , Blood , Malondialdehyde , Blood , Myocardial Infarction , Drug Therapy , Metabolism , Pathology , Myocardial Reperfusion Injury , Drug Therapy , Metabolism , Pathology , Rats, Wistar , Reactive Oxygen Species , Metabolism , Superoxide Dismutase , Blood
20.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 728-731, 2006.
Article in Chinese | WPRIM | ID: wpr-230166

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the establishment of mini-porcine myocardial ischemia (MI) model induced by thrombosis via cardiac catheterization intervention, and observe the anti-MI action of Shuangshen Ningxin Capsule (SNC).</p><p><b>METHODS</b>MI model of Chinese mini-porcine was established by injection of self-thrombus in left anterior descending coronary artery (LAD) with guiding catheter through carotid artery. The effect of SNC on MI was evaluated comprehensively by analyzing the parameters as coronary embolism, 30 dots surface mapping electrocardiogram and quantitative histology, etc.</p><p><b>RESULTS</b>LAD in the model animals was basically embolized 6 days after modeling, showing increase of amplitude and dot of ST segment elevation. After being administered with SNC for 6 days, the self-thrombus blocked LAD was recanalized and the degree and extent of MI reduced.</p><p><b>CONCLUSION</b>It is the first time to successfully establish MI model of Chinese mini-procine by thrombosis via cardiac catheterization intervention. SNC has anti-MI effect.</p>


Subject(s)
Animals , Female , Male , Capsules , Disease Models, Animal , Drugs, Chinese Herbal , Therapeutic Uses , Myocardial Ischemia , Drug Therapy , Phytotherapy , Swine , Swine, Miniature
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