[Ti-AI intermetallic compound membrane refining Chinese medicinal materials extract].

OBJECTIVE: To preliminarily evaluate the refining effect on Chinese medicinal materials extract using the microfiltration membrane of Ti-A1 intermetallic compound. METHODS: Conduct a series of microfiltration experiments on the extract of several commonly used Chinese medicinal materials (Nelumubinis Plumula and Eucommiae Folium)and compound preparation of Baihuasandi. Then, analyze the changes of traits, total solid and index components before and after filtring. RESULTS: After two stages (10 microm and 30 microm) of membrane micro-filtring, the total solid removal rates of Nelumubinis Plumula were 1.2% and 22.66%, and the remaining rates of neferine were 97.56% and 95.12%; The total solid removal rates of Eucommiae Folium were 1.2% and 22.66%, and the remaining rates of caffeotannic acid were 95.50% and 87.28%; The totalsolid removal rates of Baihuasandi were 11.09% and 14.29%, and the remaining rates of quercetin were 98.58% and 95.43%, respectively. CONCLUSION: Microfiltration membrane technique utilizing the Ti-Al intermetallic compound has a good effect in refining Chinese medicinal materials extract.

Lgr4 is a key regulator of prostate development and prostate stem cell differentiation.

Mechanisms modulating prostate cell fate determination remain unexplored. The leucine-rich repeat containing G-protein-coupled receptors (Lgr) have been identified as important stem cell markers in various tissues. Here, we investigated the roles of Lgr4/Gpr48 in prostate stem cells (PSCs) and development. Lgr4 was ubiquitously expressed during early prostate development prior to lineage specification, with adult expression restricted to a few basal cells (principally Lin(-)Sca1(+)CD49f(+)). Lgr4(-/-) mice had compromised branching morphogenesis and delayed epithelial differentiation, leading to decreased prostate size and impaired luminal cell function. In vitro prostate sphere culture revealed that Lgr4(-/-) Lin(-)/Sca1(+)/CD49f(+) cells failed to generate p63(low) cells, indicating a differentiation deficiency. Furthermore, Lgr4 ablation arrested PSC differentiation of in vivo kidney capsule prostate grafts, suggesting that Lgr4 modulates PSC properties independent of hormonal and mesenchymal effects. Analysis of neonatal prostates and prostate spheres revealed a decrease in Wnt, Sonic Hedgehog, and Notch1 expression in Lgr4(-/-) cells. Lgr4 loss blocked differentiation of prostate sphere p63(hi) cells to p63(low). Treatment with exogenous Sonic Hedgehog partially restored the differentiation of p63(hi) cells in Lgr4(-/-) spheres. Taken together, our data revealed the roles of Lgr4 in early prostate development and in stem cell differentiation through regulation of the Wnt, Notch, and Sonic Hedgehog signaling pathways.

[Cardiac metallothionein overexpression improves cardiac contractile function and attenuates oxidative stress in lipopolysaccharide-treated mice].

OBJECTIVE: This study was designed to examine the impact of the antioxidant metallothionein (MT) on cardiac contractile, intracellular Ca(2+) function and oxidative stress in lipopolysaccharide (LPS)-treated mice. METHODS: Weight and age matched adult male FVB and cardiac-specific MT-overexpressing transgenic mice were injected intraperitoneally with 4 mg/kg Escherichia Coli LPS dissolved in sterile saline or an equivalent volume of pathogen-free saline (control groups). Six hours following LPS or saline injection, cardiac geometry and function were evaluated in anesthetized mice using the 2-D guided M-mode echocardiography. Mechanical and intracellular Ca(2+) properties were examined in hearts. Cell shortening and relengthening were assessed using the following indices: peak shortening (PS)-indicative of the amplitude a cell can shorten during contraction; maximal velocities of cell shortening and relengthening (± dl/dt)-indicative of peak ventricular contractility; time-to-PS (TPS)-indicative of systolic duration; time-to-90% relengthening (TR(90))-indicative of diastolic duration (90% rather 100% relengthening was used to avoid noisy signal at baseline concentration). The 360 nm excitation scan was repeated at the end of the protocol and qualitative changes in intracellular Ca(2+) concentration were inferred from the ratio of fura-2 fluorescence intensity (FFI) at two wavelengths (360/380). Fluorescence decay time was measured as an indicator of the intracellular Ca(2+) clearing rate. Glutathione/glutathione disulfide ratio and ROS generation were detected as the markers of oxidative stress. RESULTS: Heart rate was increased while EF was reduced in LPS-FVB mice and heart rate was reduced and EF increased in MT-LPS transgenic mice [(528 ± 72) beats/min vs (557 ± 69) beats/min, (66 ± 14)% vs (42 ± 10)%, P < 0.05]. Cardiomyocytes from the LPS treated FVB mice displayed significantly reduced peak shortening (PS) and maximal velocity of shortening/relengthening (±dl/dt) associated with prolonged time-to-90% relengthening (TR(90)), these effects were attenuated in cardiomyocytes from the MT-LPS mice [PS(5 ± 1.1)% vs (7.2 ± 0.8)%, dl/dt(160 ± 15) µm/s vs (212 ± 36) µm/s, -dl/dt (175 ± 32) µm/s vs (208 ± 29) µm/s, TR(90) (0.24 ± 0.03)s vs (0.19 ± 0.02)s, P < 0.05]. LPS treated mice showed significantly reduced peak intracellular Ca(2+) and electrically-stimulated rise in intracellular Ca(2+) as well as prolonged intracellular Ca(2+) decay rate without affecting the basal intracellular Ca(2+) levels, again, these effects were significantly attenuated in MT-LPS transgenic mice. Metallothionein overexpression also ablated oxidative stress [reduced ROS generation and increased glutathione/glutathione disulfide ratio, ROS (0.35 ± 0.08) A/µg protein vs (0.24 ± 0.03) A/µg protein]. GSH/GSSG 2.1 ± 0.2 vs 2.6 ± 0.4, P < 0.05. CONCLUSION: MT overexpression improved cardiac function and ablated oxidative stress in LPS treated mice.

The aqueous extract of Asparagus officinalis L. by-product exerts hypoglycaemic activity in streptozotocin-induced diabetic rats.

BACKGROUND: The inedible bottom part of asparagus (Asparagus officinalis L.) spears, around one-third to one-half of the total length, is always discarded as by-product. Since it still contains various bioactive substances, this by-product might have potential usage in food supplements for its therapeutic effects. In this study the hypoglycaemic effect of the aqueous extract of asparagus by-product (AEA) was evaluated in a streptozotocin (STZ)-induced diabetic rat model. RESULTS: Continuous administration of AEA for 21 days significantly decreased fasting serum glucose and triglyceride levels but markedly increased body weight and hepatic glycogen level in diabetic rats. In an oral glucose tolerance test, both the blood glucose level measured at 30, 60 and 120 min after glucose loading and the area under the glucose curve showed a significant decrease after AEA treatment. CONCLUSION: The results of this study demonstrate that AEA has hypoglycaemic and hypotriglyceridaemic functions, suggesting that it might be useful in preventing diabetic complications associated with hyperglycaemia and hyperlipidaemia.

Hypolipidaemic and hypoglycaemic effects of total flavonoids from seed residues of Hippophae rhamnoides L. in mice fed a high-fat diet.

BACKGROUND: The present study was designed to investigate the hypolipidaemic and hypoglycaemic effects of total flavonoids from seed residues of Hippophae rhamnoides L. (FSH) in a high-fat diet fed mouse model. Consumption of a high-fat diet (HFD) for 4 weeks caused a significant rise of serum total cholesterol in mice. These hypercholesterolaemic mice then were orally administrated with different doses of FSH (50, 100 and 150 mg kg⁻¹ body weight) and simvastatin (20 mg kg⁻¹ body weight) for another 12 weeks under continuous HFD feeding. RESULTS: FSH administration markedly reduced total mouse body, liver, and epididymal fat pad weights. Serum total cholesterol and low density of lipoprotein-cholesterol levels were also significantly decreased by FSH treatment. Additionally, FSH significantly lowered total cholesterol and triglyceride concentrations in liver, and the results were corroborated by transmission electron microscope findings. The rise in serum glucose was significantly suppressed by FSH treatment while improving impaired glucose tolerance. CONCLUSION: These results suggest that FSH possesses hypolipidaemic and hypoglycaemic properties in mice fed a high-fat diet and could be developed as a supplement in healthcare foods and drugs.

Hypolipidemic effect of n-butanol Extract from Asparagus officinalis L. in mice fed a high-fat diet.

During industrial processing of Asparagus (Asparagus officinalis L.), around half of each spear is discarded. However, these discarded asparagus (by-products) might be used as food supplements for their potential therapeutic effects. This study evaluated the hypolipidemic effect of n-butanol extract (BEA) from asparagus by-products in mice fed a high-fat diet (HFD). Continuous HFD feeding caused hyperlipidemia, oxidative stress and liver damage in mice. Interestingly, while BEA significantly decreased the levels of body weight gain, serum total cholesterol and low density lipoprotein cholesterol, it dramatically increased the high density lipoprotein level when administered at three different doses (40, 80 or 160 mg/kg body weight) for 8 weeks in hyperlipidemic mice. In addition, BEA decreased the levels of alanine transaminase, aspartate transaminase and alkaline phosphatase in serum. Finally, superoxide dismutase activity and the total antioxidation capacity were evidently increased, while the malondialdehyde level and the distribution of lipid droplets were reduced in liver cells of BEA-treated mice. Taken together, the findings of this study suggested that BEA had a strong hypolipidemic function and could be used as a supplement in healthcare foods and drugs or in combination with other hypolipidemic drugs.

Hypolipidaemic and hepatoprotective effects of ethanolic and aqueous extracts from Asparagus officinalis L. by-products in mice fed a high-fat diet.

BACKGROUND: Asparagus (Asparagus officinalis L.) by-products, i.e. the parts of the spears discarded during industrial processing, might have potential use as food supplements for their therapeutic effects. In this study the hypolipidaemic and hepatoprotective effects of ethanolic (EEA) and aqueous (AEA) extracts from asparagus by-products were evaluated in mice fed a high-fat diet (HFD). RESULTS: Continuous HFD feeding caused obvious hyperlipidaemia and liver damage in mice. However, both EEA and AEA significantly decreased the levels of body weight gain, serum total cholesterol and serum low-density lipoprotein cholesterol in hyperlipidaemic mice when administered at a daily dose of 200 mg kg(-1) for 8 weeks. Also, serum high-density lipoprotein cholesterol levels were evidently increased in the AEA-treated group. Moreover, both EEA and AEA dramatically decreased the activities of alanine and aspartate transaminases in serum. Finally, superoxide dismutase activity and total antioxidant capacity were increased and malondialdehyde level and the distribution of lipid droplets decreased in liver cells of both EEA- and AEA-treated mice. CONCLUSION: The findings of this study suggest that both EEA and AEA have strong hypolipidaemic and hepatoprotective properties and could be used as supplements in healthcare foods and drugs or in combination with other hypolipidaemic drugs.

Effects of clopidogrel on vascular proliferation and apoptosis in an atherosclerotic rabbit model.

Inflammation, vascular proliferation. and apoptosis contribute to the process of atherosclerosis. Clopidogrel has been used to treat atherosclerosis; however, the mechanism is not entirely known. Compared with those of atorvastatin, we determined effects of clopidogrel on inflammatory factors, vascular proliferation, and apoptosis in an atherosclerosis rabbit model. New Zealand white rabbits were fed a normal diet or a high cholesterol diet for 7 weeks. The right iliac artery of animals except those in the negative control group were balloon-injured 1 week after initiation of the diet, and groups of animals were treated with clopidogrel (4 mg/kg per day), atorvastatin (2.5 mg/kg per day), or placebo (positive control group) for 6 weeks. We found that the placebo group had significant progression of atherosclerosis compared with the negative control group. In contrast, clopidogrel- or atorvastatin-treated rabbits showed a significant reduction in progression of atherosclerosis, including a low expression of high sensitivity C-reactive protein and platelet-derived growth factor, a reduced intima thickness, and reduced ratio of bcl-2/bax in the vascular wall. These results suggest that clopidogrel can retard the progression of established lesions that is related to inhibiting inflammation, cell proliferation, and promotion of cell apoptosis.

Hypoglycemic effect of aqueous extract of seabuckthorn (Hippophae rhamnoides L.) seed residues in streptozotocin-induced diabetic rats.

An extract of seabuckthorn (Hippophae rhamnoides L.) seed residues has been shown to possess hypoglycemic and hypolipidemic properties in normal mice. The present study investigated the effects of an aqueous extract of seabuckthorn seed residues (ASSR) on serum glucose, lipid profiles and antioxidant parameters in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into four groups: a normal control group; diabetic control group; diabetic groups supplemented with 5 mg/kg body weight glibenclamide (reference drug) and 400 mg/kg body weight ASSR. Diabetes in rats was induced by intraperitoneal injection of streptozotocin (45 mg/kg body weight). Vehicle (distilled water), glibenclamide and ASSR were administered orally to normal and diabetic rats once a day lasting for 4 weeks. The data showed that administration of ASSR significantly lowered the serum glucose, triglyceride and nitric oxide levels in diabetic rats. Moreover, ASSR treatment also increased serum superoxide dismutase activity and glutathione level markedly. These results show that ASSR has hypoglycemic, hypotriglyceridemic and antioxidant effects in streptozotocin-induced diabetic rats, suggesting that ASSR supplementation can be useful in preventing diabetic complications associated with hyperlipidemia and oxidative stress.

Effects of angiotensin-II receptor blockers on experimental autoimmune myocarditis.

BACKGROUND: The effects of angiotensin-II type 1 receptor blockers (ARBs) on the treatment of hypertension, heart failure, and other cardiovascular diseases have been confirmed extensively. However, recent studies have emphasized the nonhemodynamic effects of these drugs. The purpose of this study was to investigate the effects of ARBs on the development of experimental autoimmune myocarditis (EAM), and to clarify the mechanisms involved. METHODS: EAM model was induced in Lewis rats by injection of porcine cardiac myosin subcutaneously. We administered valsartan (a new ARB) to rats with EAM and measured blood pressure regularly. Echocardiography was performed to examine the cardiac function and heart structure of the rats. The severity of myocarditis was detected by histopathological evaluation. We evaluated antigen-specific T-cell proliferation responses to cardiac myosin by the lymphocyte proliferation assay and measured serum levels of Th1 and Th2 cytokines by enzyme-linked immunosorbent assay. RESULTS: There was no significant difference in the blood pressure (BP) level between the groups and cardiac function of valsartan-treated rats was significantly improved compared with untreated rats. Valsartan markedly reduced the severity of myocardial lesions and suppressed lymphocyte proliferation in rats immunized with myosin. After drug administration, Th1 cytokines (IFN-gamma and IL-2) were significantly down-regulated, while Th2 cytokines (IL-4 and IL-10) were detected to undergo up-regulation. CONCLUSIONS: The results suggest that valsartan can ameliorate EAM independent of BP-lowering effects. Some of the beneficial effects of ARBs may be due to their immunomodulatory reactions in the modification of helper T-cell balance.

Deficiency in TLR4 signal transduction ameliorates cardiac injury and cardiomyocyte contractile dysfunction during ischemia.

Toll-like receptor 4 (TLR4), a proximal signalling receptor in innate immune responses to lipopolysaccharide of gram-negative pathogens, is expressed in the heart. Accumulating evidence have consolidated the notion that TLR4 plays an essential role in the pathogenesis of cardiac dysfunction. However, the molecular mechanisms of TLR4 responsible for ischemia-induced cardiac dysfunction remain unclear. To address the signalling mechanisms of TLR4-deficiency cardioprotection against ischemic injury, in vivo regional ischemia was induced by occlusion of the left anterior descending coronary artery in wild-type (WT) C3H/HeN and TLR4-mutated C3H/HeJ mice. The results demonstrated that blunted ischemic activation of p38 mitogen-activated protein kinase and JNK signalling occurred in C3H/HeJ hearts versus C3H/HeN hearts, while ERK and AMP-activated protein kinase (AMPK) signalling pathways were augmented during ischemia in C3H/HeJ hearts versus C3H/HeN hearts. Intriguingly, ischemia-stimulated endoplasmic reticulum stress was higher in C3H/HeN hearts than that in C3H/HeJ as demonstrated by up-regulation of Grp78/BiP, Gadd153/CHOP and IRE-1alpha. Myocardial infarct, caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining demonstrated that C3H/HeN hearts suffered more damage than those of C3H/HeJ hearts during ischemia. Moreover, isolated cardiomyocytes from C3H/HeJ hearts showed resistance to hypoxia-induced contractile dysfunction compared to those from C3H/HeN hearts, which are associated with greater hypoxic activation of AMPK and ERK signalling, better intracellular Ca(2+) handling in C3H/HeJ versus C3H/HeN cardiomyocytes. These findings suggest that the cardioprotective effects against ischemic injury of hearts with deficiency in TLR4 signalling may be mediated through modulating AMPK and ERK signalling pathway during ischemia.

Cardiac-specific overexpression of insulin-like growth factor I (IGF-1) rescues lipopolysaccharide-induced cardiac dysfunction and activation of stress signaling in murine cardiomyocytes.

Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, plays a key role in cardiac dysfunction in sepsis. Low circulating levels of insulin-like growth factor 1 (IGF-1) are found in sepsis, although the influence of IGF-1 on septic cardiac defect is unknown. This study was designed to examine the impact of IGF-1 on LPS-induced cardiac contractile and intracellular Ca2+ dysfunction, activation of stress signal and endoplasmic reticulum (ER) stress. Mechanical and intracellular Ca2+ properties were examined in cardiomyocytes from Fast Violet B and cardiac-specific IGF-1 overexpression mice treated with or without LPS (4 mg kg(-1), 6 h). Reactive oxygen species (ROS), protein carbonyl formation and apoptosis were measured. Activation of mitogen-activated protein kinase pathways (p38, c-jun N-terminal kinase [JNK] and extracellular signal-related kinase [ERK]), ER stress and apoptotic markers were evaluated using Western blot analysis. Our results revealed decreased peak shortening and maximal velocity of shortening/relengthening and prolonged duration of relengthening in LPS-treated Fast Violet B cardiomyocytes associated with reduced intracellular Ca2+ decay. Accumulation of ROS protein carbonyl and apoptosis were elevated after LPS treatment. Western blot analysis revealed activated p38 and JNK, up-regulated Bax, and the ER stress markers GRP78 and Gadd153 in LPS-treated mouse hearts without any change in ERK and Bcl-2. Total protein expression of p38, JNK, and ERK was unaffected by either LPS or IGF-1. Interestingly, these LPS-induced changes in mechanical and intracellular Ca2+ properties, ROS, protein carbonyl, apoptosis, stress signal activation, and ER stress markers were effectively ablated by IGF-1. In vitro LPS exposure (1 microg mL(-1)) produced cardiomyocyte mechanical dysfunction reminiscent of the in vivo setting, which was alleviated by exogenous IGF-1 (50 nM). These data collectively suggested a beneficial of IGF-1 in the management of cardiac dysfunction under sepsis.

Chinese medicinal herb Radix Astragali suppresses cardiac contractile dysfunction and inflammation in a rat model of autoimmune myocarditis.

Radix Astragali, a Chinese medicinal herb, consists of polysaccharides and flavonoids as its main active ingredients. It has been widely used for treatment of cardiovascular diseases such as heart failure, angina pectoris, myocardial infarction and stroke in Asian countries. This study was designed to evaluate the effect of Radix Astragali on myocardial dysfunction, cardiac remodeling and morphological alteration in an experimental model of autoimmune myocarditis, a clinical condition often resulting in dilated cardiomyopathy. Experimental autoimmune myocarditis was established with a subcutaneous injection of porcine cardiac myosin into rear footpad in Lewis rats. Radix Astragali treatment was delivered via an intravenous injection (0.2 ml/100g body weight, daily) for 3 weeks. Results from transthoracic echocardiography indicated that experimental autoimmune myocarditis led to impaired myocardial contractile function which was reconciled by Radix Astragali. The experimental autoimmune myocarditis triggered profound inflammation and fibrosis in myocardium as assessed by hematoxylin and eosin (H and E) and Masson's trichrome staining. Interestingly, Radix Astragali significantly attenuated autoimmune myocarditis-induced myocardial inflammation and fibrosis. Similarly, Radix Astragali treatment alleviated autoimmune myocarditis-triggered overt lymphocyte proliferation. Furthermore, Radix Astragali significantly attenuated elevated levels of the Th1 cytokines (IFN-gamma and IL-2), and increased the Th2 cytokines (IL-4 and IL-10) in autoimmune myocarditis. Collectively, our data revealed that Radix Astragali effectively protected against cardiac functional and morphological aberrations in experimental autoimmune myocarditis.

c-Jun inhibits thapsigargin-induced ER stress through up-regulation of DSCR1/Adapt78.

The endoplasmic reticulum (ER) is exquisitely sensitive to changes in its internal environment. Various conditions, collectively termed "ER stress", can perturb ER function, leading to the activation of a complex response known as the unfolded protein response (UPR). Although c-Jun N-terminal kinase (JNK) activation is nearly always associated with cell death by various stimuli, the functional role of JNK in ER stress-induced cell death remains unclear. JNK regulates gene expression through the phosphorylation and activation of transcription factors, such as c-Jun. Here, we investigated the role of c-Jun in the regulation of ER stress-related genes. c-Jun expression levels determined the response of mouse fibroblasts to ER stress induced by thapsigargin (TG, an inhibitor of sarco/endoplasmic reticulum Ca(2+) ATPase). c-jun(-/-) mouse fibroblast cells were more sensitive to TG-induced cell death compared to wild-type mouse fibroblasts, while reconstitution of c-Jun expression in c-jun(-/-) cells (c-Jun Re) enhanced resistance to TG-induced cell death. The expression levels of ER chaperones Grp78 and Gadd153 induced by TG were lower in c-Jun Re than in c-jun(-/-) cells. Moreover, TG treatment significantly increased calcineurin activity in c-jun(-/-) cells, but not in c-Jun Re cells. In c-Jun Re cells, TG induced the expression of Adapt78, also known as the Down syndrome critical region 1 (DSCR1), which is known to block calcineurin activity. Taken together, our findings suggest that c-Jun, a transcription factor downstream of the JNK signaling pathway, up-regulates Adapt78 expression in response to TG-induced ER stress and contributes to protection against TG-induced cell death.

Relation of corrected thrombolysis in myocardial infarction frame count and ST-segment resolution to myocardial tissue perfusion after acute myocardial infarction.

OBJECTIVES: To evaluate myocardial tissue perfusion by corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and ST-segment resolution after successful percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). BACKGROUND: Early and sustained potency of infarct-related artery (IRA) has become the main goal of reperfusion therapy in patients with AMI. However, myocardial tissue perfusion may remain impaired even after the achievement of TIMI grade 3 flow of the epicardial artery without residual stenosis. METHODS: CTFC was measured after successful PCI in 63 patients with first AMI. The extent of ST-segment resolution was recorded 1 hr after reperfusion therapy. The wall motion score index (WMSI) was assessed before and 1 month after PCI. Then we studied the correlation between CTFC, ST-segment resolution, and WMSI. RESULTS: According to CTFC, the patients with TIMI grade 3 flow after PCI were divided into two groups: CTFC fast group and CTFC slow group. CTFC fast group had higher percentage of complete ST resolution (54.1% vs. 25.0%, P < 0.05) and lower percentage of no ST resolution (2.6% vs. 29.2%, P < 0.05). Improvement of WMSI in the CTFC fast group was significantly greater than that of the CTFC slow group (1.30 +/- 0.41 vs. 0.64 +/- 0.30, P < 0.05). CTFC had a significant negative correlation with the change in WMSI (r = -0.75, P < 0.01). CONCLUSIONS: Combined with ST-segment resolution, CTFC could predict risk for patients with successful reperfusion therapy after AMI and provide evidence for additional adjunctive treatment.

[Atorvastatin inhibits scavenger receptor A and monocyte chemoattractant protein-1 expressions in foam cell].

OBJECTIVE: To investigate the effects of atorvastatin on expressions of scavenger receptor A and secretion of monocyte chemoattractant protein-1 (MCP-1) in foam cells. METHODS: THP-1 cells were induced to differentiate into macrophages by PMA and treated with 0.1% BSA (control), ox-LDL (100 mg/L) or ox-LDL plus atorvastatin (5, 10, 20 micromol/L) for 24 hours. MCP-1 concentration in cell substratum was measured by ELISA. Scavenger receptor A expression was observed under fluorescent microscope after incubated with DiI-Ac-LDL. The relationship between concentration of MCP-1 and the activity of scavenger receptor A was also analyzed. RESULTS: Compared to the control cells, MCP-1 concentration in ox-LDL treated cells was significantly increased after 6 hours, peaked at 12 hours and was still significantly increased after 24 hours (all P < 0.05 vs. baseline). The activity of scavenger receptor A was also significantly increased in ox-LDL treated cells (P < 0.01 vs. control). The activity of scavenger receptor A proteins correlated positively to the concentration of MCP-1 in ox-LDL treated cells (r = 0.683, P < 0.01). Atorvastatin significantly attenuated these changes in a dose-dependent manner. CONCLUSIONS: Scavenger receptor A and MCP-1 expressions were significantly increased in the course of monocyte lines THP-1 differentiating into macrophages and foam cells. The anti-atherosclerosis effect of atorvastatin might be partly achieved by inhibiting the secretion of MCP-1 and expression of scavenger receptor A in foam cells.

Effect of clopidogrel on the inflammatory progression of early atherosclerosis in rabbits model.

Atherosclerosis is an inflammatory response of the arterial wall to 'injury', which is prominently driven by inflammatory factors. Clopidogrel reduces early atherosclerosis, however, the role of clopidogrel in modulating inflammatory progression of atherosclerosis is less investigated. We wished to determine the effect of clopidogrel on progression of established atherosclerosis, vascular inflammatory factors and compared with that of aspirin and atorvastatin. Fifty male New Zealand white (NZW) rabbits were divided into five groups randomly including negative group. The rabbits were fed with a normal diet or a high cholesterol diet for 7 weeks. The right iliac artery of animals except negative group were balloon injured 1 week after initiation of the diet, then animals were treated with clopidogrel (4 mg/kg/day), aspirin (12 mg/kg/day), atorvastatin (2.5mg/kg/day) or placebo for 6 weeks. At the end of the study, the placebo (positive) group had significant progression of atherosclerosis compared with negative group. In contrast, clopidogrel, aspirin or atorvastatin treated rabbits showed a significant reduction in progression of atherosclerosis and decreased the levels of P-selection, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in serum and vascular wall. Among three drugs, the action of clopidogrel is the most powerful in decreasing the levels of inflammatory factors. These results suggest that in a rabbit atherosclerosis model, clopidogrel retards the progression of established lesions and that this effect is paralleled by a suppression of inflammatory factors.

[Association of angiotensin I converting enzyme 2 gene polymorphism with essential hypertension in Chinese].

OBJECTIVE: To identify the genetic variants of angiotensin I converting enzyme 2 (ACE2) gene in a Chinese population and to determine whether the ACE2 gene polymorphisms are associated with essential hypertension (EH). METHODS: Seven hundred and forty-five patients with EH and 362 normal blood pressure controls were included in the study to assess the contribution of polymorphism of ACE2 gene. Direct DNA sequencing was performed to detect the single nucleotide polymorphisms (SNPs) in 20 subjects who were randomly selected from the EH patients. RESULTS: One SNP named G8790A located in the 4th base of the third intron was found in the 20 patients. The genotyping data indicate that the A allele frequency in male EH patients complicated with cardiac incompetence(55%) is significantly different from that in the control group(43.3%)(P<0.01). The A allele frequency in female patients with cardiac incompetence (56.1%) is higher than that in the controls (50.5%), but the difference does not reach statistical significance. CONCLUSION: The G8790A polymorphism may be related to the essential hypertension with cardiac incompetence in Chinese population. Additional investigation will be need to confirm the association.

[Effect of combined therapy of shenmai and compound danshen injection on myocardial reperfusion injury after percutaneous coronary intervention in patients with acute myocardial infarction].

OBJECTIVE: To explore the effect of combined therapy of shenmai and compound danshen injection (SM-DS) on myocardial reperfusion injury after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). METHODS: Thirty-eight AMI patients who received PCI were randomly divided into two groups, the 19 patients in the treated group were treated with SM-DS before and after PCI. Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in patients' venous blood were measured at different time-points, and the integrated left ventricular ejection isometric index (Tei) was determined by echocardiogram. RESULTS: As compared with before operation in the treated group, MDA was higher and SOD was lower at 2 hrs, 24 hrs after operation (P < 0.05); IL-6 and TNF-alpha were significantly lower at 24 hrs, 48 hrs and 1 week (P < 0.05, P < 0.01) and the Tei began to be improved at 24 hrs (P < 0.05) and significantly improved at 1 week after operation (P < 0.01). While in the control group, MDA was higher and SOD was obviously lower at 2 hrs and 24 hrs (P < 0.01); lowering of IL-6 and TNF-alpha appeared at 1 week (P < 0.05) and improving of Tei index revealed 1 week after operation respectively (P < 0.05). Comparison between the two groups showed significant difference in levels of MDA and SOD at 2 hrs and 24 hrs (P < 0.01); significant difference in levels of IL-6, TNF-alpha at 24 hrs, 48 hrs and 1 week; and in Tei index at 24 hrs and 1 week after operation (P <0.05). CONCLUSION: SM-DS could reduce the myocardial reperfusion injury in patients with AMI after PCI.

[Effect of different angiotensin converting enzyme inhibitors on coronary collateral circulation].

OBJECTIVE: To observe the effects of different angiotensin converting enzyme inhibitors (ACEI) on coronary collateral circulation. METHODS: Twenty-four healthy dogs underwent measurement of distolic aortic pressure (DAP) and ligation of the left anterior descending coronary artery. The distolic coronary pressure (DCP) and retrograde blood flow (Qret) were measured. Five days after the operation the dogs were randomly divided into three groups of 8 dogs: benazepril group (benazepril 10 mg qd); captopril group (captopril 12.5 mg bid) and control group (starch tablet was given). Thirty days after the operation a reflux catheter was inserted to measure the DCP and Qret again. Then the dogs were killed and their hearts were taken out to examine the pathologic changes. The angiotensin converting enzyme (ACE) activity levels in plasma and myocardium were examined by FAPGG spectrophotometry. RESULTS: (1) In the captopril group the plasma ACE activity was (24.1 +/- 0.6) U/L 10 days after medication, and 24.3 +/- 0.6 U/L twenty-five days after medication, both significantly lower than that before medication [(57.6 +/- 0.8) U/L, both P < 0.01]; in benazepril group the plasma ACE activity was (24.4 +/- 0.4) U/L ten days after medication, and (24.0 +/- 0.5) U/L 25 days after medication, both significantly lower than that before medication [(59.5 +/- 1.3) U/L, both P < 0.01]. The plasma ACE activity levels of captopril and benazepril groups, especially of the benazepril group, after medication were significantly lower than that of the control group. The tissue ACE activity levels of the captopril and benazepril groups were lower than that of the control group. (2) The values of DCP in the control and captopril group were higher after medication than before medication. A tendency of decrease of DCP was shown in the benazepril group, however, without statistical significance. (3) In the control group Qcol was (2.01 +/- 0.31) ml/min 25 days after medication, significantly than that before medication [(0.91 +/- 0.15) ml/min], the corresponding values in captopril group were (2.24 +/- 0.46) ml/min and (0.88 +/- 0.13) ml/min respectively in the captopril group and (3.18 +/- 0.27) ml/min and (0.89 +/- 0.11) ml/min respectively in the benazepril group with the value 25 days after in the benazepril group being the highest. (4) 30 days after operation collateral circulation was established in the ischemic myocardium in all 3 groups. The microvessel density in the ischemic zone of myocardium was higher than that in the nonischemic zone in all 3 groups. The microvessel density in the ischemic zone of myocardium was greater in the benazepril group than in the captopril and control groups. There was no difference in microvessel density between the captopril group and control group. CONCLUSION: Benazepril increases the microvessel density and collateral flow, promotes the creation of collateral circulation in ischemic area, but captopril has not such effects.