Influence of aspirin on platelet activation during vascular endothelial injury induced by high blood glucose fluctuations / 中国药理学通报

Aim To investigate the influence of aspirin on platelet activation during vascular endothelial injury induced by high blood glucose fluctuations .Methods In this study , "fluctuant high blood glucose cultured human umbilical vein endothelial cell ( HUVEC ) mod-el" and "human platelet-HUVEC supernate experi-mental system" were established in vitro, as well as type 2 diabetes mellitus ( T2DM) rat model with high blood glucose fluctuation in vivo. There were four groups: normal glucose ( N ) , steady high glucose (W), fluctuant high glucose ( B), and aspirin group ( ASA) .At the end of the study , the peripheral blood platelet maximum aggregation rate , levels of sE-selec-tin, von Willebrand factor ( vWF ) and platelet mem-brane protein level of CD62p were determined.Results In comparison with N group, levels of sE-selectin,vWF, the platelet maximum aggregation rate and plate-let membrane protein level of CD 62 p in W group and B group all significantly increased ( P <0.01 ) , mean-while B group significantly increased further compared with W group ( P <0.05 or P <0.01 ) .Pretreatment with ASA significantly decreased the elevated levels of sE-selectin, vWF, the platelet maximum aggregation rate and CD62p induced by high glucose fluctuations (P<0.01).Conclusions High blood glucose fluctu-ations can not only aggravate endothelial injury , but al-so promote platelet aggregation obviously , while aspirin has obvious antagonistic effects on these effects .

Size at birth and blood pressure in young adults: findings from a Brazilian birth cohort study / Tamanho ao nascer e pressão arterial em adultos jovens: achados de uma coorte de nascimentos brasileira

OBJECTIVE: To describe the prevalence of borderline blood pressure (BBP) and hypertension (HT) among young adults and to assess the association between size at birth and BBP/HT. METHODS: Data were collected from the fi rst Ribeirão Preto Birth Cohort Study conducted in the city of Ribeirão Preto, southeastern Brazil, that started in 1978-1979. Of the 6,827 singletons born in hospitals, 2,060 were assessed at 23-25 years of age. Blood samples were collected, an anthropometric assessment was performed, and information was obtained regarding occupation, schooling, life habits and chronic diseases. Blood pressure (BP) was classifi ed as: 1) BBP: systolic BP (SBP) ≥ 130 mm Hg and < 140 mm Hg and/or diastolic BP (DBP) ≥ 85 mm Hg and < 90 mm Hg; and 2) HT: SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg. A polytomic logistic regression model was used. RESULTS: BBP prevalence was 13.5% (males: 23.2%) and HT prevalence 9.5% (males: 17.7%). BBP was independently associated with male gender (relative risk [RR] 8.84; 95%CI 6.09;12.82); birth length ≥ 50 cm (RR 1.97; 1.04;3.73); body mass index (BMI) ≥ 30 kg/m2 (RR 3.23; 2.02;5.15); and high waist circumference (RR 1.61; 1.13;2.29), while HT was associated with male gender (RR 15.18; 8.92;25.81); BMI ≥ 30 kg/m2 (RR 3.68; 2.23;6.06); high waist circumference (RR 2.68; 1.77;4.05); and elevated blood glucose (RR 2.55; 1.27; 5.10), but not with birth length. CONCLUSIONS: The prevalence of BBP and HT among young adults of this cohort was higher in males than females. Greater birth length was associated with BBP, but not with HT, whereas birth weight was not associated with either BBP or HT. Adult risk factors explained most of the increase in the levels of BBP and HT.

OBJETIVO: Descrever a prevalência de pressão arterial limítrofe (PAL) e hipertensão (HT) entre adultos jovens e avaliar a associação entre tamanho ao nascer e PAL/HT. MÉTODOS: Dados foram coletados do primeiro estudo brasileiro de coorte de nascimentos em Ribeirão Preto (sudeste do Brasil), iniciado em 1978/79. De 6.827 recém-nascidos de parto único hospitalar, 2.060 foram avaliados aos 23/25 anos. Foram realizadas coleta de sangue, avaliação antropométrica e obtidas informações sobre ocupação, escolaridade, hábitos de vida e doenças crônicas. Pressão arterial (PA) foi classificada em: 1) PAL: PA sistólica (PAS) ≥ 130 e < 140 mm Hg e/ou PA diastólica (PAD) ≥ 85 e < 90 mmHg; 2) HT: PAS ≥ 140 e/ou PAD ≥ 90 mm Hg. Foi aplicado modelo de regressão logística politômica. RESULTADOS: A prevalência de PAL foi de 13,5% (homens 23,2%) e a de HT, 9,5% (homens 17,7%). PAL foi independentemente associada com sexo masculino (RR 8,84; IC95%: 6,09;12,82), comprimento ao nascer ≥ 50 cm (RR 1,97; 1,04; 3,73), índice de massa corporal (IMC) ≥ 30 kg/m² (RR 3,23; 2,02; 5,15) e circunferência de cintura alterada (RR 1,61; 1,13;2,29), enquanto HT associou-se com sexo masculino (RR 15,18; 8,92;25,81), IMC ≥ 30 kg/m² (RR 3,68; 2,23;6,06), circunferência de cintura alterada (RR 2,68; 1,77;4,05) e glicemia elevada (RR 2,55; 1,27;5,10), mas não com comprimento ao nascer. CONCLUSÕES: As prevalências de PAL e HT entre os adultos jovens dessa coorte foram maiores em homens que em mulheres. Maior comprimento ao nascer foi associado com PAL, mas não com HT, enquanto peso ao nascer não foi associado com PAL ou HT. Fatores de risco do adulto explicaram a maioria dos aumentos de PAL ou HT.

Effect and mechanism of high glucose on expression of hypoxia-inducible factor 1α in cultured neonatal rat cardiomyocytes under hypoxia and non-hypoxia conditions / 中国糖尿病杂志

Objective To investigate the effect and mechanism of different high concentrations glucose(Glu) on the expression of hypoxia-inducible factor 1α(HIF-1α) in cultured neonatal rat eardiomyocytes under hypoxia and non-hypoxia conditions. Methods Neonatal rat cardiomyocytes were cultured for 6 hours under different conditions and were divided into 6 groups:①Negative control group (5.5 mmol/L Glu) ; ②hypoxia mimicking cobalt chloride(Cocl_2) group(5.5 mmol/L Glu + 400 μmol/L cocl_2 ) ;③Different high concentrations Glu groups: (11.1 mmol/L, 22.2 mmol/L, 33.3 mmol/L Glu);④cocl_2 +different high concentrations Glu groups(11.1 mmol/L Glu +400 μmol/L cocl_2,22.2 mmol/L Glu +400 μmol/L cocl_2, 33.3 mmol/L Glu+400 μmol/L cocl_2);⑤High concentrations Glu + antioxidant α-tocopherol group(33.3 mmol/L Glu + 100 μmol/L α-tocopherol) ; ⑥ High concentrations Glu+antioxidant α-tocopherol+cocl_2 group(33.3 mmol/L Glu+400 μmol/L cocl_2+100 μmol/L α-tocopherol). The effect of high concentrations Glu, cocl_2 and high concentrations Glu plus cocl_2 on the expression of HIF- 1α mRNA and protein in cultured neonatal rat cardiomyocytes, as well as the effect of high concentrations Glu plus antioxidant α-tocopherol, high Glu concentrations plus cocl_2 and antioxidant α-tocopherol on the expression of HIF- 1α mRNA and protein were observed. Results 1. Compared with negative control group(5.5 mmol/L Glu), the 'expression of HIF- 1α was increased under cocl_2 mimicked hypoxia(5.5 mmol/L Glu+400 μmol/L cocl_2, 11.1 mmol/L Glu+400 μmol/L cocl_2 ,22.2 mmol/L Glu+400 μmol/L cocl_2,33.3 mmol/L Glu+400 μmol/L cocl_2). 2. The expression of HIF- 1α was increased gradually after the increasing of Glu concentrations(5.5 mmol/L, 11.1 mmol/L, 22.2 mmol/L and 33.3 mmol/L Glu).3.The expression of HIF-1α was decreased gradually after the increasing of Glu concentrations under certain cocl_2 plus different high concentrations Glu (5.5 mmol/L Glu+400 μmol/L cocl_2, 11.1 mmol/L Glu+400 μmol/L cocl_2, 22.2 mmol/L Glu+400 μmol/L cocl_2,33.3 mmol/L Glu+400 μmol/L cocl_2). 4. Under high concentration Glu plus antioxidant α-tocopherol (33.3 mmol/L Glu+100 μmol/L α-tocopherol) ,the expression of HIF- 1α was less increased than the same high Glu concentration(33.3 mmol/L Glu). 5. Under high Glu concentration plus cocl_2 (33.3 mmol/L Glu+400 μmol/L cocl_2), the expression of HIF- 1α increased less than that of the same high Glu concentration plus antioxidant α-tocopherol and cocl_2 (33.3 mmol/L Glu+400 μmol/L Cocl_2+ 100 μmol/L α-tocopherol). Conclusions High glucose increases the expression of HIF-1α under non-hypoxia, but blunts the expression of HIF-1α under hypoxia in cultured neonatal rat cardiomyocytes. Some mechanisms such as ROS (reactive oxygen species) signal transduction system and oxidative stress may be involved in it.

Effects of intermittent high glucose on islet β-cell function and apoptosis in GK rats / 中华内分泌代谢杂志

Objective To compare the effects of intermittent high blood glucose and consistent hilgh blood glucose on pancreatic islet β-cell function and β-cell apoptosis in GK rats.Methods Twenty-two male GK rats were randomly divided into 2 groups consisting of consistent hish blood glucose group(HG)and intermittent high blood glucose group(FG).Eleven male Wistar rats were used as normal glucose controls(NG).The fluctuating high blood glucose animal model was induced by intraperitoneal injection of insulin and glucose at different time for six weeks.Intraperitoneal injection glucose tolerance test and insulin release test were performed.The area under curve of glucose(AUCg).the area under carve of insulin(AUCi)/AUCg and the ratio of insulin increment to blood glucose increment 15 min after glucose load(Δ115'/ΔG15')were calculated routinely.Then the pancreatic slides were stained with insulin antibody.The apoptotic β cells in islets were detected and quantified by the TUNEL technique.Results(1)The fasting plasma glucose and 15,30,60,and 120 min plasma glucose levels after glucose loading in FG group were significantly higher than those in control group(all P<0.01),and AUCg was also markedly increased[(1 012.14±82.62 vs 813.60±56.70)ng·ml~(-1)·h~(-1)·10~4,P<0.01].Insulin levels of FG group at 15,30,60,and 120 rain after glucose loading were significantly lower than those in HG group[(0.554± 0.18 vs 0.95±0.28.0.43±0.17 vs 0.85±0.21,0.47±0.11 vs 0.76±0.16,0.58±0.13 vs 1.08±0.26)ng/ml,P<0.05],along with decreased AUCi/AUCg and Δ115'/ΔG15'[(9.56±2.53 vs 21.36±4.16)×10~(-7);(3.95±3.45 vs 27.02±8.62)×10~(-7),both P<0.05].(2)Image analysis of pancreatic islet immunocytoehemistry showed that the insulin staining positive area,area ratio and total density of insulin positive cells per islet were significantly lower in FG group than those in HG group(P<0.05).(3)The percentage of β-cell apoptosis in the FG group was statistically higher than that in the HG group[(24.17±7.25 vs 16.55±5.11)%,P<0.01].Conclusion Compared with the consistent high blood glucose,intermittent high glucose could lead to further impairment of β-cell function and increased β-cell apoptosis may partially contribute to this process.