打鼾与高尿酸交互作用对儿童青少年代谢综合征的影响

目的 研究打鼾和高尿酸及其交互作用对儿童青少年代谢综合征(metabolic syndrome, MetS)的影响,为儿童青少年MetS针对性防控提供理论依据。方法 从参加深圳市中小学生营养健康与生长发育评估与监测的7～17岁儿童青少年中获得人口学资料、打鼾、人体测量和生化指标等。Logistic回归模型评估打鼾、高尿酸与MetS的关联并利用相加模型来评估两者交互作用对MetS的影响。结果 4 466名参与者的年龄中位数为12.16岁,2 454 (54.9%)为男性。MetS、打鼾和高尿酸的检出率分别为3.2%、29.3%和33.4%。打鼾频次<1次/周、1～2次/周和≥3次/周与MetS患病存在正向关联,且呈逐渐上升的趋势(P䥺Symbol|@@0.001)。打鼾(OR=2.085, 95%CI:1.462～2.902)和高尿酸(OR=4.741, 95%CI:3.144～7.148)均与MetS患病相关。此外,打鼾频次、打鼾与高尿酸对MetS患病均不存在相乘交互作用,但打鼾和高尿酸对MetS患病存在相加交互作用[超额相对危险度=3.801(0.060～7.542),交互作用...     

一氧化碳对CYP2E1介导的微粒体酒精氧化应激的保护作用

目的探讨诱导I型血红素氧合酶(heme oxygenase-1,HO-1)催化血红素产生的代谢产物一氧化碳(CO)对大鼠肝微粒体细胞色素P4502E1(cytochrome P4502E1,CYP2E1)酶活性影响及其介导的酒精性氧化应激的保护作用。方法超速离心法制备大鼠肝脏微粒体,加入血红素(hemin)、血红蛋白(Hb)、不同剂量的CO释放剂CORM-2(carbonmonoxide-releasing molecules-2),检测CYP2E1酶活性;在微粒体酒精氧化反应体系中加入血红素、血红蛋白及CORM-2,检测微粒体超氧化物歧化酶(SOD)活力及谷胱甘肽(GSH)、丙二醛(MDA)及氧自由基(ROS)水平。结果 hemin处理后肝微粒体CYP2E1的酶活性下降,联合Hb后CYP2E1酶活性明显升高,外源性CO则显示出类似的CYP2E1酶抑制效应;针对乙醇孵育的肝微粒体,hemin处理后明显抑制了肝微粒体MDA和ROS水平的升高,有效维持了GSH水平和SOD活力,联合Hb处理后明显抑制了上述保护效应,外源性CORM-2也显示出类似的保护效应,而灭活的CORM-2则无明显的保护效应。结论 CO对大鼠肝微粒体酒精性氧化应激具有保护作用,其机制可能与CO对CYP2E1酶活性的直接抑制有关。     

HFE genetic variability and risk of alcoholic liver disease: A meta-analysis

Studies examining the association of hemochromatosis (HFE) gene polymorphisms and susceptibility to alcoholic liver disease (ALD) yielded inconsistent results. Thus, we performed a metaanalysis to investigate whether the variations in HFE gene increase the risk of ALD. The studies published up to Feb. 2014 were identified by searching PubMed/MEDLINE, ISI Web of Science, EMBASE and China National Knowledge Infrastructure databases, which was complemented by screening the references of the retrieved studies. For all genotypes and alleles, the odds ratios (ORs) with 95% confidence intervals (CIs) according to the heterogeneity were pooled using fixed-effect model. Sixteen studies with 1933 cases and 9874 controls were included for this meta-analysis. C282Y/C282Y, C282Y/wild type, H63D/wild type and C282Y/H63D were found not to be associated with susceptibility to ALD, but increased risk of H63D/H63D (OR: 1.52, 95% CI: 1.05–2.22, P=0.029) was observed for ALD when compared to total control. Comparison of ALD patients with alcoholics without liver damage revealed a significant association of D allele, as well as a marginal association of H63D/wild type with ALD, while H63D/H63D was not significantly associated with ALD although increased value of OR was obtained. The presence of Y allele and other genotypes yielded insignificant findings when ALD patients were compared with alcoholics without liver damage. No evident publication bias or significant heterogeneity among studies was detected in this meta-analysis. In conclusion, our metaanalysis showed a marginal higher prevalence of H63D variant in ALD but did not support an increased risk of C282Y mutation.     

白藜芦醇对大鼠肾氧化损伤保护作用

目的探讨白藜芦醇对高糖高脂饮食大鼠肾氧化损伤的保护作用。方法大鼠分为正常对照组、高糖高脂组、白藜芦醇低、中、高剂量组,13周后处死大鼠,测定血糖血脂、肾组织氧化应激水平、抗氧化酶活性及肾脏过氧化物酶激活受体α(PPARα)、羟甲基戊二酸单酰辅酶A合成酶(HMGCS2)mRNA表达水平。结果高糖高脂饮食13周后,高糖高脂组大鼠体重为(453.00±19.54)g,明显高于正常对照组(368.75±25.24)g和高剂量白藜芦醇组(400.40±30.39)g(t=4.545、2.991,P<0.05);高糖高脂组大鼠肾脏总抗氧化能力(T-AOC)、超氧化物歧化酶(T-SOD)分别为(1.22±0.34)、(2.69±0.13)U/(mg.Pro),明显低于正常对照组的(0.27±0.03)、(2.43±0.07)U/(mg.pro)(t=3.491,P=0.003;t=2.793,P=0.011)。结论高糖高脂饮食大鼠肾内处于明显的氧化应激状态,白藜芦醇对高糖高脂饮食引起的氧化性肾损伤有保护作用。     

白藜芦醇对高糖高脂饲料大鼠胰岛素敏感性的影响

目的研究白藜芦醇对高能量饮食大鼠胰岛素敏感性的影响。方法清洁级雄性Wistar大鼠35只,随机分为对照组(正常Cont和高糖高脂对照组HFG)和低、中、高白藜芦醇剂量组(HFG+R1,2,3)。12W后分别进行口服葡萄糖耐量试验和胰岛素耐量试验。13W末,断头处死,测空腹血糖和血胰岛素,计算稳态评估胰岛素抵抗指数(HOMA-IR指数)。实时荧光定量PCR技术检测主动脉磷脂酰肌醇3激酶p85αmRNA水平变化。结果与高糖高脂组比,白藜芦醇显著降低大鼠体重,调节血脂(P<0.05)。白藜芦醇还可显著降低大鼠血胰岛素水平和HOMA-IR指数,改善高糖高脂饮食诱导的大鼠葡萄糖耐量和胰岛素耐量异常(P<0.05)。高糖高脂饮食使大鼠p85αmRNA表达降低,中、高剂量的白藜芦醇则可遏制高糖高脂的有害作用(P<0.05)。结论白藜芦醇可提高高糖高脂饮食大鼠胰岛素敏感性,预防胰岛素抵抗的发生,其机制可能与调节主动脉PI3K p85αmRNA水平有关。     

白藜芦醇诱导HO-1对酒精性肝细胞的保护作用

目的白藜芦醇(resveratrol)是非黄酮类的多酚化合物,具有多种有益的生物学效应。本研究目的观察白藜芦醇对酒精导致的人原代肝细胞损伤的保护作用及机制。方法经体外灌流、分离培养人原代肝细胞。测定白藜芦醇20μmol/L对酒精致肝细胞LDH释放率的影响。人原代肝细胞给予不同受试物(100 mmol/L酒精,20μmol/L白藜芦醇,25μmol/L Znpp9(锌原卟啉Ⅸ:zinc protoporphyrin-IX))24h,观察HO-1酶活性变化,孵育上清液AST,LDH释放水平,肝细胞内MDA,GSH含量变化。结果白藜芦醇可显著升高酒精致肝细胞LDH释放率的EC50(从700 mmol/L上升至1050 mmol/L);白藜芦醇可使肝细胞HO-1酶活性明显增加,并可显著抑制酒精导致的肝细胞AST,LDH释放,降低肝细胞内MDA水平,提高GSH含量。但是HO-1抑制剂Znpp9却明显降低了白藜芦醇对酒精导致的肝细胞损伤的保护作用。结论白藜芦醇对酒精导致的人肝细胞损伤具有保护作用,这种保护作用与其诱导的HO-1酶活性升高有关。