Ginsenoside Rb1 Protects Human Umbilical Vein Endothelial Cells against High Glucose-Induced Mitochondria-Related Apoptosis through Activating SIRT3 Signalling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether ginsenoside Rb1 (Rb1) can protect human umbilical vein endothelial cells (HUVECs) against high glucose-induced apoptosis and examine the underlying mechanism.@*METHODS@#HUVECs were divided into 5 groups: control group (5.5 mmol/L glucose), high glucose (HG, 40 mmol/L) treatment group, Rb1 (50 µ mol/L) treatment group, Rb1 plus HG treatment group, and Rb1 and 3-(@*RESULTS@#Rb1 ameliorated survival in cells in which apoptosis was induced by high glucose (P<0.05 or P<0.01). Upon the addition of Rb1, mitochondrial and intracellular reactive oxygen species generation and malondialdehyde levels were decreased (P<0.01), while the activities of antioxidant enzymes were increased (P<0.05 or P<0.01). Rb1 preserved the mitochondrial membrane potential and reduced the release of Cyt-c from the mitochondria into the cytosol (P<0.01). In addition, Rb1 upregulated mitochondrial biogenesis-associated proteins (P<0.01). Notably, the cytoprotective effects of Rb1 were correlated with SIRT3 signalling pathway activation (P<0.01). The effect of Rb1 against high glucose-induced mitochondria-related apoptosis was restrained by 3-TYP (P<0.05 or P<0.01).@*CONCLUSION@#Rb1 could protect HUVECs from high glucose-induced apoptosis by promoting mitochondrial function and suppressing oxidative stress through the SIRT3 signalling pathway.

Ginsenoside Rb1 Attenuates Human Umbilical Vein Endothelial Cells Senescence Induced by High Glucose through Sirt3/SOD2 Pathway / 中山大学学报(医学科学版)

@#Abstract】 【Objective】To investigate the effect and mechanism of ginsenoside Rb1 attenuating human umbilical vein endothelial cells(HUVEC) senescence induced by high glucose through Sirt3/SOD2 pathway.【Methods】The senescence of HUVEC induced by high glucose(40 mmol/L)was assessed by senescence-associated β-galactosidase(SA-β-Gal)staining,and the expression of plasminogen activator inhibitor 1(PAI-1)and P16. Annexin V-FITC/PI was performed to measure apoptotic effect. The expression of sirtuins 3(Sirt3)and superoxide dismutase 2(SOD2)was detected by western blot. Meanwhile,the level of intracellular malondialdehyde(MDA)and the activity of SOD2 were measured.【Results】Treatment of HUVEC with high glucose for 24 hours induced premature senescence instead of apoptosis,as indicated by a larger proportion of the cells stained with SA-β-Gal and the up-regulated expression of PAI-1 and P16. Pretreatment of HUVEC with ginsenoside Rb1(40 μmol/L)could reverse endothelial cell senescence,as indicated by the reduced SA-β-Gal positive cells and the down-regulated expression of PAI-1 and P16. Furthermore,ginsenoside Rb1 pretreatment upregulated the protein expression of Sirt3 and SOD2,and eventually increased the activity of SOD2 and decreased the level of MDA.【Conclusion】Ginsenoside Rb1 could antagonize high glucose-induced premature senescence of HUVEC via Sirt3/SOD2 signaling pathway.

Hydrogen sulfide attenuates human umbilical vein endothelial cell senes-cence via modulation of Sirt1/eNOS pathway / 中国病理生理杂志

AIM:To explore the role of Sirt1/eNOS signalling pathway in the protective effect of hydrogen sul-phide(H2S)against endothelial cell senescence induced by high glucose.METHODS:High glucose(33 mmol/L)was applied to induce senescence in primary human umbilical vein endothelial cells(HUVECs).The cell viability,the propor-tion of senescence-associated β-galactosidase(SA-β-Gal)positive cells and the plasminogen activator inhibitor 1(PAI-1) expression were detected to assess the senescence model.Mean while,Sirt1 siRNA was used to examine the effect of Sirt 1 on eNOS expression and the senescence-related parameters.RESULTS: Treatment of HUVECs with high glucose de-creased the cell viability slowly with a larger proportion of the cells stained with SA-β-Gal, and the protein expression of PAI-1 was dramatically increased.The increased cell viability,reduced SA-β-Gal positive cells and decreased protein ex-pression of PAI-1 were detected after sodium hydrosulfide(NaHS,100 μmol/L)treatment.Furthermore,NaHS treatment upregulated the protein expression of Sirt 1 and eNOS,and eventually increased the production of nitric oxide(NO).CON-CLUSION:Exogenous H2S modulates Sirt1/eNOS/NO pathway to prevent HUVECs against high glucose-induced senes-cence.

Effects of external counterpulsation on shear stress and production of nitric oxide and cGMP in canines with myocardial infarction / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of external counterpulsation (ECP) on shear stress and signal transduction in canines with myocardial infarction.</p><p><b>METHODS</b>Nineteen healthy dogs were randomly divided into control, ischemia, and ischemia plus ECP groups. Myocardial infarction was induced in the latter two groups by ligation of the left anterior descending artery (LAD). Serum and aorta NO levels of the dogs were determined by modified nitrate reductase method, and serum and aorta cyclic guanosine monophosphate (cGMP) levels by radioimmunoassay.</p><p><b>RESULTS</b>The shear stress in the truncus brachiocephalicus decreased after LAD ligation, but increased significantly after 2 h of ECP treatment. Serum and aorta NO levels in ECP and control groups were significantly higher than those in the ischemic group (P<0.05). Serum and aorta cGMP levels in control group and ECP group after LAD ligation were also significantly higher than those in the ischemic group (P<0.05).</p><p><b>CONCLUSION</b>ECP can increase the shear stress and increase NO and cGMP levels in dogs with myocardial ischemia, which might be an important mechanism of ECP for protection of the ischemic myocardium.</p>

Effects of irbesartan on nitric oxide system in the heart of diabetic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of irbesartan for heart protection and on heart nitric oxide (NO) system in diabetic rats.</p><p><b>METHODS</b>Thirty adult male Wistar rats were randomly divided into three equal groups, namely control group, diabetes group and irbesartan group. Streptozotocin (STZ, 50 mg/kg) was injected to the abdomen to induce diabetes in the rats. After treatment for 12 weeks, the rats were sacrificed and the urine volume, body weight, ratio of heart to body weight, plasma glucose and glycosylated hemoglobin (HbA1c) were measured. NO levels in the serum and myocardium were determined. Inducible nitric oxide synthase (iNOS) expression was determined by immunohistochemistry, and iNOS mRNA detected by RT-PCR.</p><p><b>RESULTS</b>Urine volume, ratio of heart to body weight, plasma glucose, HbA1C, NO levels in the urine, blood and myocardium in diabetic and irbesartan rats were significantly greater than those of normal controls (P<0.05). The ratio of heart to body weight and NO levels of urine, serum and heart tissue in rats of irbesartan group were significantly decreased as compared with those of diabetes rats (P<0.05). Myocardium iNOS mRNA and protein expression decreased significantly in irbesartan group, but not in diabetes group.</p><p><b>CONCLUSIONS</b>The abnormality in NO and iNOS mRNA expression might be related to diabetic cardiomyopathy. Irbesartan can decrease iNOS mRNA and protein expressions and reduce NO levels in STZ-induced diabetic rats.</p>

Effects of Sini decoction on vascular stenosis after iliac artery balloon injury and oxidative stress in rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of Sini decoction (SND) in preventing vascular restenosis and protecting against oxidative stress after rabbit iliac artery balloon injury.</p><p><b>METHODS</b>Twenty-four male New Zealand albino rabbits were equally randomized into control group, model group and SND group. Rabbits in the control group were fed with common forage, and those in the model and SND groups with high-fat diet. Two weeks later, the iliac arteries of the rabbits in the latter two groups were subjected to balloon injury. Four weeks after the operation, the rabbits were killed and the vascular structure was observed by scanning electron microscope and optical microscope, with the serum cholesterol level, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level determined.</p><p><b>RESULTS</b>Scanning electron microscopy showed that the endothelial cell lining in the iliac artery of the control and SND group remain regular, but the arteries in the model group presented with desquamated and exposure of the collagen fibril beneath the endothelium. Optical microscope revealed narrowed vascular lumen, thicken intima and numerous arteriosclerotic plaques in the model group in comparison with the control group, whereas the vascular lumen and intima thickness remained basically normal in SND group. The levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were decreased with high-density lipoprotein cholesterol levels increased in SND group, which was not observed in the model group. The serum SOD activity was higher in the control group than in the model and SND groups, but SND group had higher serum SOD activity than the model group. The serum MDA level was lower in the control group than in the other two groups, but SND group had lower MDA level than the model group.</p><p><b>CONCLUSION</b>SND can alleviate intimal hyperplasia and vascular stenosis in injured rabbit iliac artery, possibly in relation to increased SOD activity and decreased lipid peroxidation as a result of SND treatment.</p>