Atherosclerosis In Rats Research Articles

Anti-atherosclerotic effect of Longxuetongluo Capsule in high cholesterol diet induced atherosclerosis model rats

Chinese dragon’s blood, the red resin of Dracaena cochinchinensis, one of the famous traditional medicines, has been used to promote blood circulation, disperse blood stasis, stop bleeding, relieve pain and muscle regeneration for thousands of years. The aims of this study were to evaluate the anti-atherosclerotic effect of Longxuetongluo Capsule (LTC), which made by total phenolic compounds of Chinese dragon’s blood, in high cholesterol diet (HCD)-induced atherosclerosis model rats and explore the possible mechanism. Atherosclerosis rats were induced by administration of HCD for 4 weeks and treated with atorvastatin (2.08mg/kg/d) or various concentrations of LTC (81, 162 and 324mg/kg/d) for additional 4 weeks. Body weight (BW), lipid profiles, serum VCAM-1, ICAM-1, MCP-1, AST and ALT were then tested. Histopathological evaluation of aorta and liver were determined by hematoxylin and eosin staining. NF-κB expression in aorta was detected by Immunohistochemical staining. Meanwhile, the inhibition effects of LTC on the migration and proliferation and Intracellular Ca2+ levels induced by PDGF-BB were also evaluated in rat aortic smooth muscle cells (A7r5). The results demonstrated that LTC produced a significant anti-atherosclerotic activity in terms of reduction in serum lipids and lipoprotein profile, VCAM-1, ICAM-1, MCP-1, AST, ALT levels, and increase in HDL-c level compared to atherosclerotic group. Rats treated with LTC not only attenuated the pathological region and atheroma formation, but also reduced hepatic steatosis and inflammatory cell infiltration. Immunohistochemical analysis showed LTC reduced NF-κB expression in aorta. Furthermore, PDGF-BB induced proliferation and migration of A7r5 and intracellular calcium rise were also abrogated by LTC. The results indicate that LTC prevents atherosclerosis and fatty liver by controlling lipid metabolism, the underlying mechanism may attributed to its anti-inflammation activity, regulation of the vascular smooth muscle function and intracellular calcium signaling.

Effect of leech on VSMCs in early atherosclerosis rats via p38MAPK signaling pathway

To explore the effect of leech on proliferation and apoptosis of vascular smooth muscle cells(VSMCs) in early atherosclerosis rats via p38MAPK signaling pathway and investigate its possible mechanism. Biochemical analyzer was used to examine the regulation of leech on levels of triglycerides(TG), total cholesterol(TC), low-density lipoprotein(LDL-C), and high-density lipoprotein(HDL-C) in blood lipid of rats. The expression of transforming growth factor-beta 1(TGF-β1) in serum was detected by ELISA. Immunological histological chemistry (IHC) was taken to measure the expression levels of proliferating cell nucleus antigen(PCNA) and cell apoptosis proteinase-3(Caspase-3), while the protein expression levels of MKK3, p38 and C-myc were detected by Western blot. In addition, hematoxylin and eosin(HE) staining was used to observe the morphological change of thoracic aortas. The results showed that leech decreased the levels of TC, LDL-C obviously and increased HDL-C, suppressed the expression levels of TGF-β1 and PCNA, up-regulated Caspase-3, down-regulated the expression levels of MKK3, p38, and C-myc protein. HE staining indicated that it could inhibit intimal thickening and reduce plaque formation. The above results indicated that leech may affect the protein expression of the p38MAPK signaling pathway to inhibit proliferation and promote the apoptosis of VSMCs via reducing blood lipid levels and suppressing TGF-β1, aiming at inhibiting intimal thickening and reducing plaque formation, tand then slowing down the process of early atherosclerosis.

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

This study aimed to identify the role of microRNA-22 (miR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), miR-22 mimic, miR-22 inhibitor and miR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between miR-22 and NLRP3. MiR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β, IL-6, IL-10 and IL-18 levels. The results indicated that the atherosclerosis group significantly decreased miR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the miR-22 mimic group and significantly reduced in the miR-22 inhibitor group. The miR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the miR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1β, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the miR-22 mimic group. In contrast, in the miR-22 inhibitor group, IL-1β, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. Our findings indicated that miR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD.

Anti-atherosclerotic activity of root bark of Premna integrifolia Linn. in high fat diet induced atherosclerosis model rats

Premna integrifolia Linn. is a medicinal plant used in “Dhasamula” drug preparation of Ayurvedic systems of medicine in the treatment of various ailments like bronchitis, dyspepsia, liver disorders, piles, constipation, hyperlipidemia and fever. The anti-atherosclerotic activity of hydroalcoholic extract (HAE) of root bark of P. integrifolia was evaluated in high fat diet induced atherosclerosis rats. Sixty Wistar rats were divided into six groups: the first group served as control, the second group was fed with high fat diet and the other three groups were fed with high fat diet along with various concentrations of HAE and the last group was treated with atorvastatin for 30 days. Lipid and lipoprotein profile, atherogenic index, and cardiac markers and histopathological evaluation of aorta were determined in high fat diet induced atherosclerosis rats. HAE of P. integrifolia produced a significant and dose-dependent anti-atherosclerotic activity in terms of reduction in lipids and lipoprotein profile, atherogenic index, HMG-CoA reductase activity, marker enzymes such as lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), alteration in collagen and calcium contents, mild mineralization and focal rupture of intima and media of aorta was noticed in treated groups as compared to the control. The results suggested that anti-atherosclerotic activity of HAE of P. integrifolia Linn. was due to its modulatory activity on metabolic pathway of lipid. The results contribute to the validation of the traditional use of Agnimantha in high fat diet induced atherosclerosis rats.

Influence of crocetin on high-cholesterol diet induced atherosclerosis in rats via anti-oxidant activity together with inhibition of inflammatory response and p38 MAPK signaling pathway.

The present study aimed to investigate the effect and possible mechanism of action of crocetin on the high cholesterol diet (HCD) induced atherosclerosis rat. The Wistar rats were used in the current investigation. The rats were divided into following group, Group I: control, Group II: HCD induced AS, Group III: AS + crocetin (25 mg/kg), Group IV: AS + crocetin (50 mg/kg) and Group V: AS + Simvastatin, respectively. AS was induced in the rats using the vitamin D3 and HCD. The rats received the pre-determined treatment for the 10 weeks. After the study period, the level of lipid profile, malonaldehyde (MDA) and superoxide dismutase (SOD) were also estimated. The proinflammatory cytokines viz., tumor necrosis factor (TNF)-α and interleukin (IL)-6 were scrutinized using the ELISA kits. We also estimated the expression of phosphorylated p38 (p-p38) MAPK using the Western blot techniques. The results revealed that the AS was successfully induced in the rats. The AS control group rats showed the modulated level of lipid profile, and decreased the level of the SOD and boost the level of the MDA as compared with the normal control. However, crocetin thrived in enhancing the lipid profile toward the standard value in the normal control group rats. The crocetin and simvastatin group rats significantly inhibited the expression of the p-p38 MAPK as compared to the AS group rats. In conclusion, the current investigation revealed that the crocetin reduced the HCD induced dyslipidemia in the Wistar rats, the possible mechanism of action may be connected to the antioxidative, down regulating of p-p38 MAPK and antiinflammatory effect by crocetin.

Effects of phospholipid complexes of total flavonoids from Persimmon (Diospyros kaki L.) leaves on experimental atherosclerosis rats

The total flavonoids from Persimmon leaves (PLF), extracted from the leaves of Diospyros kaki L. Dispryosl and Ebenaceae, is reported to possess many beneficial health effects. However, the oral bioavailability of PLF is relatively low due to its poor solubility. In the present study, the phospholipid complexes of total flavonoids from Persimmon leaves (PLF-PC) was prepared to enhance the oral bioavailability of PLF and to evaluate its antiatherosclerotic properties in atherosclerosis rats in comparison to PLF. A HPLC-MS method was developed and validated for the determination of quercetin and kaempferol in rats plasma to assess the oral bioavailability of PLF-PC. The effect of PLF (50mg/kg/d) and PLF-PC (equivalent to PLF 50mg/kg/d) on atherosclerosis rats induced by excessive administration of vitamin D (600,000IU/kg) and cholesterol (0.5g/kg/d) was assessed after orally administered for 4 weeks. The relative bioavailabilities of quercetin and kaempferol in PLF-PC relative to PLF were 242% and 337%, respectively. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) in serum were measured by an automatic biochemistry analyzer. The morphological changes of aorta were observed with optical microscopy. According to the levels of biochemical parameters in serum and the morphological changes of aorta, PLF-PC showed better therapeutic efficacy compared to PLF. Thus, PLF-PC holds a promising potential for increasing the oral bioavailability of PLF. Moreover, PLF-PC exerts better therapeutic potential in the treatment of atherosclerotic disease than PLF.

Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, Reduces Rho Kinase Activity in Atherosclerosis.

PurposeIncreased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis.Materials and MethodsStudies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg·kg-1·d-1) and high-dose darapladib (50 mg·kg-1·d-1) interventions were then administered over the course of 2 weeks.ResultsThe serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p<0.05 vs. sham group), whereas nitric oxide (NO) production was reduced. Levels of TC, LDL-C, CRP, Lp-PLA2, and Rho kinase activity were respectively reduced in darapladib groups, whereas NO production was enhanced. When compared to the low-dose darapladib group, the reduction of the levels of TC, LDL-C, CRP, and Lp-PLA2 was more prominent in the high-dose darapladib group (p<0.05), and the increase of NO production was more prominent (p<0.05). Cardiomyocyte apoptosis of the high-dose darapladib group was also significantly reduced compared to the low-dose darapladib group (p<0.05). However, there was no significant difference in Rho kinase activity between the low-dose darapladib group and the high-dose darapladib group (p>0.05).ConclusionDarapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.

Yindanxinnaotong, a Chinese compound medicine, synergistically attenuates atherosclerosis progress.

Yindanxinnaotong (YD), a traditional Chinese medicine, has been introduced to clinical medicine for more than a decade, while its pharmacological properties are still not to be well addressed. This report aimed to explore the anti-atherosclerosis properties and underlying mechanisms of YD. We initially performed a computational prediction based on a network pharmacology simulation, which clued YD exerted synergistically anti-atherosclerosis properties by vascular endothelium protection, lipid-lowering, anti-inflammation, and anti-oxidation. These outcomes were then validated in atherosclerosis rats. The experiments provided evidences indicating YD’s contribution in this study included, (1) significantly reduced the severity of atherosclerosis, inhibited reconstruction of the artery wall and regulated the lipid profile; (2) enhanced antioxidant power, strengthened the activity of antioxidant enzymes, and decreased malondialdhyde levels; (3) significantly increased the viability of umbilical vein endothelial cells exposed to oxidative stress due to pretreatment with YD; (4) significantly reduced the level of pro-inflammatory cytokines; (5) significantly down-regulated NF-kB/p65 and up-regulated IkB in the YD-treated groups. Overall, these results demonstrated that YD intervention relieves atherosclerosis through regulating lipids, reducing lipid particle deposition in the endothelial layer of artery, enhancing antioxidant power, and repressing inflammation activity by inhibiting the nuclear factor-kappa B signal pathway.

Effect on the expression of VEGF and HIF‐1 alpha in atherosclerosis rat myocardial with oral HSP60 (618.8)

Objective to study the effect on the expression of vascular endothelial growth factor (VEGF) and hypoxia inducing factor ‐ 1 alpha (HIF ‐ 1 alpha) in atherosclerosis(AS) rat myocardial with oral heat shock protein 60 (HSP60) .Methods 40 four weeks male SD rats, weight 100 + 10 g, were randomly divided into 4 groups: the healthy control group (group C), atherosclerosis group (AS group), oral HSP60 group before building AS model (H1 group), oral HSP60 group after building AS model (H2 group), 10 rats in each group. AS model was made by high fat feed. At 180 days age, the rats were executed after obtaining the rats blood and myocardial. The gene and protein expression of rats myocardial VEGF and HIF ‐ 1 alpha were detected by reverse transcription ‐ polymerase chain reaction (RT‐PCR) and immunohistochemical.Results The VEGF gene expression in rats myocardial of group C, AS group, H1group and H2 group respectively are 0.374±0.039, 0.869±0.049, 0.443±0.031 and 0.583±0.041; the gene expression of HIF ‐ 1 alpha respectively are 0.455±0.056, 0.936±0.034, 0.553±0.048 and 0.625±0.063; the protein expression of VEGF respectively are 4.46±0.47, 9.17±0.58, 5.28±0.37 and 8.14±0.49; the protein expression of HIF ‐ 1 alpha respectively are 5.77±0.71,13.87±0.43,7.01±0.61and 0.45±0.80.Conclusion The gene and protein expression of VEGF and HIF ‐ 1 alpha in atherosclerotic rats myocardial enhanced compared with normal control group. Oral HSP60 can reduce the gene and protein expression of VEGF and HIF ‐ 1 alpha in myocardial, and reduce the degree of myocardial ischemia anoxic injury and vascular endothelial inflammatory response. Moreover, the earlier oral, the better results.Grant Funding Source: Supported by the Science and technology development projects in Shanxi Province (No. 2011004)

Endurance exercise training inhibits neointimal formation via enhancement of FOXOs expression in balloon-induced atherosclerosis rat model.

[Purpose]This study investigated the effect of endurance exercise on neointimal formation, endothelial-dependant relaxation and FOXO expression in balloon-induced carotid arteries of rats.[Methods]Male SD(Sprague-Dawley) rats of 8 weeks ages were randomly divided into 3 groups; Sham-operated control (SO, n=10), Balloon-induced control (BIC, n=10), and Balloon-induced exercise (BIE, n=10). Endurance exercise training was performed on treadmill (18 m/min, 0% grade, 60 min/day, 5 days/week, 4 weeks).[Results]Body weight is significantly reduced in BIE compared with BIC. Neointiaml formation in BIC was significantly higher than SO, but it was significantly recovered in BIE compared with BIC. Endothelial-dependent relaxation in BIC was significantly lower than SO, but it was significantly recovered in BIE compared with BIC and expression of FOXO1 and FOXO3a also were significantly increased BIE compared with BIC.[Conclusion]These data suggest that endurance exercise inhibits neointimal formation and endothelial-dependent relaxation via FOXO expression in balloon-induce atherosclerosis rat model.

Neuroendocrine mechanisms of left ventricular dysfunction stimulated by anger stress in rats with atherosclerosis-a putative role of natriuretic peptide

ObjectiveTo investigate the role of natriuretic peptide in the process of left ventricular dysfunction caused by emotional stress. MethodsAdult male SD rats (n=30) and Wistar rats (n=60) were selected in this study. Atherosclerosis models were induced with high-fat diet and excess VD3 injection (eight consecutive weeks), and anger stress models were prepared by resident-intruder stress experiment (two consecutive weeks). Furthermore, left ventricular functions were examined by high-resolution echocardiograph, after which left ventricular myocardium and coronary arteries were prepared for pathological section and observed with electron microscope. At the same time, the hypothalamus, medulla oblongata and left ventricular myocardium were also prepared for pathological sections to detect the localization and expression of ANP, BNP and NPR-A with immunofluorescence and western blot. ResultsWe found that left ventricular functions of atherosclerosis or emotional stress modeled rats were both inferior to the healthy ones and superior to the combined (atherosclerosis and emotional stress) modeled ones (P<0.05). We also found that atherosclerosis and emotional stress could both cause morphological changes of left ventricular cells and capillary which contribute to apoptosis and hyperblastosis. Further more, there was NPR-A distributed in hypothalamus, medulla oblongata, as well as left ventricular tissues with the same express trend between groups, with atherosclerosis modeled rats the highest and the healthy rats the lowest. ConclusionsThe results of our study suggest that anger stress could cause an excess consumption of ANP, BNP and NPR-A in nervous and cardiovascular system which inhibit the compensatory self-repair function of atherosclerosis rats, leading to a promotion of fibrosis and lipid peroxidation, offering insight into the neuroendocrine mechanisms of left heart function obstacle.

Antiatherogenic Effect of Losartan in the Hyperlipidemic Rat

Background: Angiotensin II is a powerful growth stimulant that can lead to smooth muscle hyperplasia in vascular wall.Objectives: The present study was aimed to find out the anti-atherosclerotic effects of angiotensin II receptor blocker losartan.Methodology: This experimental animal study was carried out in the Laboratory of the Department of Pharmacology &amp; Therapeutics at Banghabandhu Sheik Mujib Medical University (BSMMU) Dhaka from July 2008 to June 2009. Healthy Long-Evans Norwegian male rats aged between 3-4 months with an weight of 180 to 200 gm were randomly selected and were divided into 3 groups designated as group A, B and C. Group A was fed on standard rat diet; group B was fed soybean oil and group C was fed a 2% cholesterol enriched diet which was the suspension of cholesterol powder in soybean oil. After 8 weeks 10 rats of each group were sacrificed and remaining 20 rats of group C were continued to the part II of the experiment and divided into two groups known as group I which was cholesterol fed control group and group II which were losartan treated group. After 8 weeks all the rats of two groups were sacrificed. Blood from each rat was collected to measure the lipid profile and malondialdehyde (MDA) level within erythrocyte. The aorta was separated and intima-media ratio was measured by using Image-pro plus software.Results: Losartan induces a significant reduction in serum lipids (p&lt;0.001) and in atherosclerotic lesion size (p&lt;0.001). It also significantly reduces the oxidative stress by reduction of malondialdehyde (MDA) level (p&lt;0.001).Conclusions: In a atherosclerosis rat model, losartan reduces the oxidative stress and the neointimal inflammation and this could due to direct inhibition of angiotensin II in the arterial wall.DOI: http://dx.doi.org/10.3329/jssmc.v5i2.20765J Shaheed Suhrawardy Med Coll, 2013;5(2):99-102

Study on anti-atherosclerotic effect of suxiao jiuxin pill and its mechanism.

Suxiao Jiuxin Pill is composed of Ligusticum wallichii, Borneolum Syntheticum and other drugs; it has qi promoting and blood circulation activating, meridian dredging and pain relieving efficacies. The objective of this paper is to study the effect of Suxiao Jiuxin Pill (quick-acting heart reliever), in atherosclerosis (AS) rat model and explore the mechanism for its prevention and treatment of AS. AS rat model was established by high cholesterol diet and single intra-peritoneal injection of increased dose of vitamin D3. Compared with the model group, Suxiao Jiuxin Pill medium-and high-dose groups and atorvastatin group can effectively regulate lipid metabolism. We conclude that Suxiao Jiuxin Pill has a good hypo-lipidemic effect, and can inhibit the occurrence and development of AS.

Fluorescent probe for highly selective and sensitive detection of hydrogen sulfide in living cells and cardiac tissues

A coumarin-based fluorescence chemoprobe was developed and evaluated for the selective and sensitive detection of hydrogen sulfide in degassed PBS buffers and fetal bovine serum. Fluorescence detection of hydrogen sulfide in living cells was also successfully achieved using two-photon confocal fluorescence imaging. Further in situ visualization of endogenous H(2)S was realized in cardiac tissues of normal rats and atherosclerosis (AS) rats.

Influence of new Xuefuzhuyu decoction on IgG and C3, C4 of peripheral blood in atherosclerosis rat

Objective To explore the influence of new Xuefuzhuyu decotion on IgG,C3 and C4 of peripheral blood in atherosclerosis rats.Methods Healthy adult Wister rats were selected and randomly divided into blank group,AS model group,new Xuefuzhuyu decoctioin low dosage group,the new Xuefuzhuyu decoctioin high dosage group,and positive control group,with 13 cases in each group.Vitamin D3 joint high fat feeding method was adopted to establish atherosclerosis rat model.Medicine lavage began on the first day of experiment.Low dosage new Xuefuzhuyu decoctioin,high dosage new Xuefuzhuyu decoctioin,and atovastatin were administrated to the new Xuefuzhuyu decoctioin low dosage group,the new Xuefuzhuyu decoctioin high dosage group,and positive control group respectively,and distilled water 15 ml/kg · d-1 was administrated to both the blank group and the AS model group.The weight of body was detected each week in each group for regulating the administrated dosage.After medicine lavage was performed for successive 8 weeks,blood was obtained from abdominal aorta for detecting IgG,C3,C4 by immune scattering method.Results The value of IgG,C3 and C4 were (8.110±0.720)g/L,(1.591±0.143)g/L,(0.390±0.33)g/L in the AS model group,(8.000±0.840)g/L,(1.564± 0.132) g/L,(0.396±0.36)g/L new Xuefuzhuyu decoctioin low dosage group,(7.250±0.740)g/L,(1.390±0.150)g/L,(0.326±0.153)g/L new Xuefuzhuyu decoctioin high dosage group and (7.240±0.400) g/L,(1.414 ± 0.104) g/L,(0.330±0.164) g/L in the positive control group,all of which werehigher than the blank group (5.810±0.820)g/L,(0.943±0.124)g/L,(0.330±0.164)g/L with statistically significant difference (P＜0.05).Each value of IgG,C3 and C4 in the new Xuefuzhuyu decoctioin high dosage group and the positive control group were lower than the AS model group and the new Xuefuzhuyu decoctioin low dosage group,with a statistically significant difference(P＜0.05).There was no significant difference between new Xuefuzhuyu decoctioin high dosage group and the positive control group (P＞0.05).Conclusion New Xuefuzhuyu decoction can ameliorate IgG,C3 and C4 of peripheral blood in atherosclerosis rats.Its function was similar to atorvastatin. Key words: New Xuefuzhuyu decoction; Atherosclerosis; Immune globulin IgG; C3; C4

The effect of diosgenin on interleukin-6 in atherosclerosis rats

Objective To investigate the effect of diosgenin tablet on interleukin-6 in the serum and artery of experimental atherosclerosis (AS) rats.Methods Sixty male SD rats were assigned randomly into five groups:group of sham operation (GSO,n =12),group of model (GM,n =12),group of Aspirin (GA,n =12),group of Diosgenin tablet in small dosage (GDS,n =12),and group of Diosgenin tablet in large dosage (GDL,n =12).After 7 days,the balloon-injured carotid artery angioplasty was performed except GSO.After 3 months,rats were killed.The rats' carotid arteries were stained with hematoxylin-eosin.Image analysis system was applied to measure the area of lumina and the thickness of wall to evaluate the ratio of W to L.Their blood IL-6 was detected.The expression of IL-6 in the aorta was measured with western blot.Results In the injured side,the W/L ratios of carotid artery in GDL and GDS(0.615±0.040、0.753±0.043)were much thinner than that of model group (0.803±0.043).That of GDL was thinner than GA (0.759±0.049).Compared with the model group (59.636±4.874)pg/ml,the level of serum IL-6 was decreased in GDL and GDS [ (42.582 ±4.724)pg/ml、(49.055 ±4.791) pg/rnl],GDL was much lower than GA[ (52.563 ±4.581) pg/ml].Western blot method showed that the levels of IL-6 in GDL and GDS (0.296±0.016、0.435±0.015)were significantly decreased compared with GM (0.455 ±0.026).GDL was significantly lower than GA (0.426±0.012).Conclusion Diosgenin can reduce the levels of serum and arteries IL-6 in the experiment atherosclerosis rats. Key words: Diosgenin; Atherosclerosis; Interleukin-6

Dan-Shen-Yin has integrated protective effects in diabetic atherosclerosis rat models

Dan-Shen-Yin (DSY) is a famous traditional Chinese formula. We determined its integrated protective effects mechanisms of DSY in diabetic atherosclerosis rat model. DSY (5 or 10 g/kg/day for 4 weeks) was orally administrated to the diabetic atherosclerosis rats, which were induced by nitric oxide inhibition ( L-NAME in drinking water, 1 mg/ml) plus high-fat diet. At the end of the experiments, the serum level of malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and GSH-peroxidase (GPX) activities and the serum level of glutathione(GSH) were measured; The concentrations of circulating ini¬‚ammatory markers C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-a (TNF-α) and serum fructosamine were determined, daily food and water intakes were measured and body weights were recorded every week. Also, we determined the total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the mRNAs expression of monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and CD36 mRNA in aorta. The results demonstrated that DSY had no direct effect in lowering serum fructosamine, but can produce a higher survival rate less body weight loss and more water intake in diabetic atherosclerosis in GK ratsi¼Œwhich may be through anti-oxidation, anti-inflammation, regulating blood lipid, inhibiting expression of genes related to foam cell formation in rat aorta. Dan-Shen-Yin may be used as a promising agent for both prophylaxis and treatment of diabetic atherosclerosis. Key words: Chinese medicine formula, Dan-Shen-Yin, diabetic atherosclerosis, oxidative stress, inflammation, blood lipid, genes related to foam cell formation, diabetic GK rats.

Time dependence for vascular effects of water-soluble components of diesel exhaust in atherosclerosis rats

ObjectiveAmbient particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve translocation of particles to the bloodstream and impairment of endothelial function. Whether the direct impairment is time-dependent...

Effects of Louxie mixture on vascular reactivity in atherosclerosis rats

Objective To investigate the effect of Chinese medicine Louxie mixture on vascular reactivity in atherosclerosis rats. Methods Forty male rats were randomly divided into four groups: the control group (A group, n＝10) was fed with normal diet; the model group (B group, n＝10), atorvastatin treated group (C group, n＝10 and Louxie mixture group (D group, n＝10) were fed with high fat/cholesterol diet. Atorvastatin 10 mg/kg·d-1 was administered to C group and Louxie mixture to D group for 10 weeks by gavages. Serum endothelin-1 (ET-1), nitric oxide (NO) and nitric oxide syntheses (NOS) were observed in different groups before and after the treatment. Vascular reactivity of aortic rings was measured by both the sodium nitroprusside(SNP)-induced endothelium-independent relaxation (NEDR) and the acetylcholine (Ach)-induced endothelium-dependent relaxation (EDR) in different groups. Results After treatment, the (19.03±1.72)μmol/l; NOS (24.78±0.25)U/ml vs (15.36±0.24U/ml), P＜0.01], while the level of ET-1in B levels of NO and NOS in B group were significantly lower than those in A group [NO(35.73±3.72)μmol/l vs group was higher than that in A group [(34.58±4.00) pg/ml vs (117.58±5.34)pg/ml,P＜0.01]. The levels of NO and NOS were significantly increased and the level of ET-1 was decreased in C and D groups after the treatment [NO(C: 31.30±1.96 umol/l;D: 32.85±3.70 umol/l); NOS (C: 21.96±1.07 U/ml ; D: 19.78± 1.20U/ml ); ET (C:58.26±5.14 pg/ml; D:59.30±5.73 pg/ml), P＜0.01]. The activities of NEDR were similar in four groups[SNP Emax (A: 97.33±1.31; B: 98.24±1.04;C: 97.52±1.09; D: 97.91±1.59)%, P＞0.05], but the level of EDR in the B group (P＜0.01) was the lowest among four groups [Ach Emax (A: 72.65±3.31; B: 32.68±2.39;C: 61.63±2.07; D: 57.58±2.43)%, P＜0.01]. Conclusion Chinese medicine Louxie mixture can protect vascular function in atherosclerosis rats. Key words: Louxie mixture; Vascular reactivity; Nitric oxide; Endothelin-1; Nitric oxide syntheses

Effects of Suxiao Jiuxin Pill ( ) on Oxidative Stress and Inflammatory Response in Rats with Experimental Atherosclerosis

To observe the preventive role of Suxiao Jiuxin Pill (see text) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. The AS rat model was established by a high fat diet and a large dose of calcium (vitamin D3, 0.6 million U/kg, i.p, once). Sixty healthy male adult Sprague-Dawlay (SD) rats were randomly divided into 6 groups, a normal control group (N), a model group (M), a SX low dose group (SXL), a SX middle dose group (SXM), a SX high dose group (SXH), and an atorvastatin group (ATO) (n = 10 in each group). The rats in the treatment groups were given with the specific drugs from the first day by oral administration, and the normal control group and the model group were given with normal saline for 12 weeks. Afterwards, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the content of oxidized low density lipoprotein (ox-LDL) in the serum were detected. In addition, the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) proteins were tested by Western-blot method. The serum ox-LDL and MDA level significantly decreased, SOD activity increased in the SX middle, high dose groups and the atorvastatin group compared to the model group (all P < 0.05). While the expression of PPARgamma and NF-kappab proteins significantly decreased in the SX low, middle, high dose groups and the atorvastatin group compared to the model group (all P < 0.01), with the best effect in the SX high dose group .These results indicate that SX could elevate the activity of serum SOD, decrease serum level of MDA and ox-LDL, and reduce the expression of PPARgamma and NF-kappaB proteins. SX plays an important role in anti-inflammation and inhibition of oxidative stress, which possibly are the mechanism of its preventing and treating atherosclerosis.