Syk对高糖诱导的H9c2心肌细胞凋亡的影响及其机制研究

目的 探讨脾酪氨酸激酶(Syk)对高糖诱导的H9c2心肌细胞凋亡的影响及其机制.方法 将体外培养的H9c2心肌细胞分为5组:对照组(5.5 mmol/L葡萄糖,NG组)、高糖组(33 mmol/L葡萄糖,HG组)、Syk抑制剂对照组(5.5 mmol/L葡萄糖+1μmol/L BAY,NG+ BAY组)、Syk抑制剂高糖组(33 mmol/L葡萄糖+1μmol/L BAY,HG+ BAY组)、甘露醇高渗透压对照组(5.5 mmol/L葡萄糖+27.5 mmol/L甘露醇,OC组).采用Western印迹方法检测磷酸化Syk(p-Syk)、cleaved-caspase-1及Bax、Bcl-2的蛋白水平;逆转录PCR检测caspase-1、Bax、Bcl-2 mRNA的表达;流式细胞仪检测H9c2心肌细胞凋亡率;MTT比色法检测细胞活力.结果 与NG组相比,HG组H9c2心肌细胞活力下降(F=37.3,P<0.05)、凋亡率增加(F=46.5,P<0.05),OC组、NG+ BAY组细胞凋亡率与细胞活力差异均无统计学意义(P均>0.05);且HG组p-Syk、cleaved-caspase-1及Bax表达增加,Bcl-2表达降低(F=8.4、80.5、7.6、37.4,P均<0.05),caspase-1及Bax mRNA表达升高,Bcl-2 mRNA表达降低(F=130.7、17.8、7.18,P均<0.05);与HG组相比,HG+ BAY组细胞活力升高(F=37.3,P <0.05)、细胞凋亡率降低(F=46.5,P<0.05),且cleaved-caspase-1及Bax表达降低,Bcl-2表达水平升高(F =80.5、7.6、37.4,P均<0.05),caspase-1及Bax mRNA表达降低,Bcl-2 mRNA表达升高(F=130.7、17.8、7.18,P均<0.05).结论 在高糖条件下,Syk可诱导心肌细胞凋亡,其作用是通过调控Bax、Bcl-2的表达.     

间歇性低氧大鼠模型心肌氧化应激损伤变化及依达拉奉的干预作用

目的:通过建立间歇性低氧(IH)大鼠模型,探讨IH对大鼠心肌氧化应激损伤的影响及其可能作用机制,并进一步了解依达拉奉的干预作用,为临床阻塞性睡眠呼吸暂停低通气综合征及其相关心血管并发症的研究及防治提供新思路。方法:选取健康雄性Wistar大鼠80只,随机分为正常对照(NC)组、IH组、IH+依达拉奉组、IH+生理盐水(NS)组,每组20只。采用气体控制装置向密闭模拟舱中充入氮气、氧气及压缩空气的方法建立IH大鼠模型。造模4周后,检测大鼠血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)及心肌组织丙二醛(MDA)、超氧化物歧化酶(SOD)、羟自由基的含量;测定心肌细胞线粒体腺嘌呤核苷三磷酸(ATP)水平;光镜、透射电镜观察心肌形态学及超微结构改变;反转录-聚合酶链反应技术检测心肌组织Bcl-2、Bax、半胱氨酸蛋白酶3(Caspase-3) mRNA的表达情况。结果:(1)与NC组相比,IH组及IH+NS组LDH、CK、CK-MB、MDA、羟自由基含量明显增加,Bax、Caspase-3 mRNA表达明显升高( P值均<0.05);而SOD活力显著降低,ATP含量显著减少,Bcl-2 mRNA表达明显下降( P值均<0.05)。(2)光镜和透射电镜下,NC组心肌组织未见明显损伤,而IH组及IH+NS组心肌组织的形态学及超微结构均受损。(3)经依达拉奉干预后,血清LDH、CK、CK-MB及心肌组织MDA、羟自由基含量明显降低,Bax、Caspase-3 mRNA表达下降( P值均<0.05);SOD活力明显升高,ATP含量增加,Bcl-2 mRNA表达水平升高( P值均<0.05);且光镜及电镜下心肌组织损伤程度得到一定缓解。(4)心肌细胞Caspase-3 mRNA表达水平与CK( r=0.575)、CK-MB( r=0.460)、MDA( r=0.643)、羟自由基( r=0.454)、Bax mRNA( r=0.741)呈正相关,与ATP( r=-0.525)、Bcl-2 mRNA( r=-0.578)呈负相关。 结论:(1)IH可通过增加氧化物、降低抗氧化物及激活Bcl-2、Bax、Caspase-3引起大鼠心肌氧化应激损伤;(2)IH所致的心肌氧化应激损伤可能通过线粒体介导的细胞凋亡实现;(3)依达拉奉对IH所致的大鼠心肌损伤具有干预作用。     

褪黑素通过介导线粒体自噬改善糖尿病心肌梗死后心肌损伤

目的 探讨褪黑素通过介导线粒体自噬对糖尿病(DM)心肌梗死(MI)后心肌损伤的保护作用及相关机制。方法 将32只C57BL/6J雄性小鼠按照随机数表法随机分为4组,每组8只:(1)假手术组(sham组);(2)糖尿病组(DM组);(3)糖尿病急性心肌梗死组(DMI组);(4)糖尿病急性心肌梗死+褪黑素组(DMI+Mel组)。4周后行超声心动图检测小鼠心脏功能。取心脏行切片染色,检测小鼠心肌间质纤维化程度和心肌细胞凋亡水平。培养H9c2细胞,分为以下4组:(1)对照组(CON组);(2)高糖高脂组(HG/HF组);(3)高糖高脂缺氧组(HG/HF+hypoxia组);(4)HG/HF+hypoxia+Mel组。行相应处理后,采用蛋白质印迹法检测B细胞淋巴瘤-2蛋白(Bcl-2)、含半胱氨酸的天冬氨酸蛋白水解酶-3蛋白(Caspase-3)、Bcl-2关联X蛋白(Bax)和微管相关蛋白1轻链3-β(LC3)、死骨片蛋白1(P62)、帕金蛋白(Parkin)等线粒体自噬相关蛋白的表达,采用荧光素酶法检测细胞内三磷酸腺苷(ATP)浓度。采用SPSS 25.0统计软件进行数据分析。根据数据类型,分别采用方差分析和Dunnett法进行组间比较。结果 与sham组相比,DMI组和DMI+Mel组小鼠的左心室射血分数(LVEF)和左室短轴缩短率(LVFS)显著降低;左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、心肌细胞横截面积、间质纤维化程度和细胞凋亡率显著升高,差异均有统计学意义(P＜0.05)。与DMI组相比,DMI+Mel组小鼠的心功能明显改善;LVESD、LVEDD、心肌细胞横截面积、间质纤维化程度和细胞凋亡率显著降低,差异均有统计学意义(P＜0.05)。与CON组相比,HG/HF组和HG/HF+hypoxia组细胞Bax、Caspase-3、P62表达显著升高,Bcl-2、LC3-Ⅱ/LC3-Ⅰ及Parkin水平显著降低,细胞内ATP含量显著降低,差异均有统计学意义(P＜0.05)。与HG/HF组和HG/HF+hypoxia组相比,HG/HF+hypoxia+Mel组细胞Bax、Caspase-3、P62表达显著降低,Bcl-2、LC3-Ⅱ/LC3-Ⅰ、Parkin水平显著升高,细胞内ATP含量显著升高,差异均有统计学意义(P＜0.05)。结论 褪黑素可通过增强线粒体自噬减轻糖尿病心肌梗死后心肌细胞的损伤,从而改善心脏功能。     

柚皮素对高糖诱导的H9c2心肌细胞凋亡及Nrf2/ARE信号通路的影响

目的]探讨柚皮素(NAR)对高糖(HG)诱导的大鼠心肌细胞(H9c2)凋亡及核因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)信号通路的影响。 [方法]将培养的H9c2细胞分为对照组(正常糖量)、HG组(35.5 mmol/L葡萄糖)、HG＋NAR低、中、高浓度组(35.5 mmol/L葡萄糖＋6.25、12.5、25.0 μmol/L NAR)。用噻唑蓝法检测H9c2细胞增殖活性;流式细胞术检测细胞凋亡;二氯二氢荧光素二乙酸酯荧光探针染色法检测细胞内活性氧(ROS)水平;Western blot法检测Nrf2、血红素加氧酶1(HO-1)、Bax、Caspase-3、Bcl-2蛋白表达水平。 [结果]经HG处理的H9c2细胞增殖活性、Nrf2、HO-1、Bcl-2蛋白表达水平显著降低,细胞凋亡率、ROS水平、Bax、Caspase-3蛋白表达水平显著升高(P＜0.05)。经HG与NAR共同处理H9c2细胞后,NAR低、中、高浓度组H9c2细胞增殖活性、Nrf2、HO-1、Bcl-2蛋白表达水平显著升高,细胞凋亡率、ROS水平、Bax、Caspase-3蛋白表达水平显著降低(P＜0.05)。 [结论]NAR可抑制HG诱导的H9c2细胞凋亡,其作用机制可能与激活Nrf2/ARE信号通路密切相关。     

原花青素对缺血再灌注大鼠心肌细胞凋亡及凋亡相关基因蛋白表达的影响

目的:观察原花青素对缺血再灌注大鼠心肌细胞凋亡相关基因半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、B型白细胞/2型淋巴细胞样蛋白(Bcl-2)和凋亡相关基因Bcl-2相关X蛋白(Bax)蛋白表达的影响,探讨原花青素在大鼠缺血再灌注心肌细胞凋亡中发挥的作用及可能的调控机制。方法:40只雄性SD大鼠随机等分为4组,即正常组,模型组,原花青素低剂量组[原花青素50 mg/(kg·d)],原花青素高剂量组[原花青素100 mg/(kg·d)],灌胃给药,每天1次,连续2周。末次给药后结扎冠状动脉左前降支(LAD)30 min再灌注120 min,建立大鼠心肌缺血再灌注模型。测定肌酸激酶同工酶(CK-MB)活性、心肌梗死面积;用Western blot检测各组细胞凋亡相关基因Caspase-3、Bcl-2、Bax蛋白表达;原位末端转移酶标记(TUNEL)法检测心肌细胞凋亡。结果:与正常组比较,模型组大鼠CK-MB活性显著增强、心肌梗死面积增大,心肌细胞凋亡指数升高,Caspase-3、Bax蛋白表达增强,Bcl-2蛋白表达、Bcl-2/Bax降低(P0.05);与模型组比较,原花青素高、低剂量组大鼠CK-MB活性显著减弱、心肌梗死面积减小,细胞凋亡指数显著降低,Caspase-3、Bax蛋白表达显著减弱,Bcl-2蛋白表达、Bcl-2/Bax增加(P0.05)。结论:原花青素可拮抗缺血再灌注大鼠心肌细胞凋亡,其机制可能与Caspase-3、Bax蛋白表达降低,Bcl-2表达升高,Bcl-2/Bax比例增加有关。     

体外心脏震波对大鼠心肌梗死后心肌凋亡的影响

目的研究体外心脏震波治疗(CSWT)对大鼠心肌梗死后(MI)心肌细胞凋亡及凋亡蛋白的影响。方法结扎大鼠左冠状动脉前降支建立大鼠急性心肌梗死模型,随机分为假手术(Sham)组(n=10)、MI组(n=10)及CSWT组(n=10)。CSWT治疗4 w后,取各组心肌样本进行TUNEL检测观察心肌细胞凋亡,Masson染色观察心肌纤维化,Western印迹检测Bax、Bcl-2和Caspase-3蛋白表达。结果与Sham组相比,MI和CSWT组心肌细胞凋亡指数及纤维化程度均增高,Bax和Caspase-3表达显著上调,Bcl-2表达明显下调(P0.05);而CSWT组较MI组,心肌细胞凋亡指数及纤维化程度均降低,Bax和Caspase-3表达下调,Bcl-2则表达上调(P0.05)。结论大鼠心肌梗死后心肌凋亡明显增加,体外心脏震波可抑制大鼠心肌梗死后细胞凋亡,减轻左心室纤维化。     

银杏叶提取物对大鼠急性心肌缺血再灌注时心肌细胞凋亡及凋亡相关基因表达的影响

目的 探讨银杏叶提取物(EGB)对大鼠心肌缺血再灌注时心肌细胞凋亡及凋亡相关基因表达的影响.方法 采用结扎左冠状动脉前降支(LAD)30 min,再灌注2 h复制大鼠心肌缺血再灌注模型,分别以缺口末端标记法(TUNEL)及免疫组织化学法检测心肌凋亡细胞、心肌细胞Bcl-2、Bax基因的蛋白表达的变化.结果 缺血再灌注(IR)组心肌细胞凋亡数量显著高于假手术组(P<0.01),EGB组心肌细胞凋亡明显受到抑制(P<0.01).IR组和EGB组Bax、Bcl-2、P53基因蛋白表达均明显增加(P<0.01);EGB明显促进Bcl-2基因表达,同时抑制Bax、P53基因表达(P<0.01),Bcl-2和Bax的比值也随之升高.结论 EGB可明显下调Bax和P53基因的蛋白表达,上调Bcl-2基因的蛋白表达,从而显著抑制心肌缺血再灌注损伤(MIRI)后心肌细胞凋亡.     

哈巴苷对H2O2诱导的大鼠心肌细胞H9c2氧化应激损伤的保护作用

目的探究哈巴苷(HG)对大鼠心肌细胞氧化应激损伤的作用。方法将H9c2细胞随机分为对照组(H9c2组)、哈巴苷组、H2O2组和H2O2+哈巴苷组,用H2O2处理细胞,复制氧化损伤模型。用哈巴苷(4μmoL)处理细胞,CCK8检测细胞增殖,Hoechst染色检测细胞凋亡,二氯荧光乙酰乙酸盐(DCF)法检测细胞内活性氧(ROS),根据试剂盒说明书检测上清液中超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽(GSH)浓度,Westernblot检测细胞凋亡相关蛋白Bcl-2、Bax、Caspase-3和Caspase-9的表达。结果与H9c2组比较,H2O2组心肌细胞增殖倍数明显降低,哈巴苷作用细胞4d后,H2O2+哈巴苷组心肌细胞增殖倍数明显高于H2O2组;同时,与H9c2组比较,H2O2组细胞凋亡率明显升高;与H2O2组比较,H2O2+哈巴苷组细胞凋亡率显著降低;H2O2还能显著诱导H9c2细胞Bax、Caspase-3和Caspase-9的表达,抑制Bcl-2表达;HG能显著减弱H2O2诱导Caspase-3和Caspase-9表达和抑制Bcl-2表达的作用;此外,H2O2组细胞内ROS活性及上清液中SOD和GSH浓度明显低于H9c2组,MDA浓度明显高于H9c2组,H2O2+哈巴苷组细胞内ROS活性及SOD和GSH浓度明显高于H2O2组,MDA浓度明显低于H2O2组。结论哈巴苷能通过抑制氧化应激抑制心肌细胞H9c2凋亡。     

通心络干预的心肌微血管内皮细胞条件培养液对大鼠心肌细胞凋亡的影响

目的:探讨受损的心肌微血管内皮细胞对大鼠心肌细胞凋亡的影响及通心络的干预作用。方法:制备3种心肌微血管内皮细胞条件培养液:正常心肌微血管内皮细胞(RCMECs)条件培养液,同型半胱氨酸(Hcy)诱导损伤的RCMECs条件培养液和通心络干预的RCMECs条件培养液。将大鼠胚胎H9c2心肌细胞分为4组:(1)正常对照组:弃去原培养基,换为无血清细胞培养基(DMEM);(2)N-CM组:弃去原培养基,换为正常RCMECs条件培养液;(3)H-CM组:弃去原培养基,换为Hcy诱导损伤的RCMECs条件培养液;(4)T-CM组:弃去原培养基,换为通心络干预的RCMECs条件培养液。JC-1试剂检测细胞线粒体膜电位(MMP);流式细胞仪检测细胞活性氧簇(ROS)水平;活细胞成像系统动态观察各组心肌细胞凋亡情况;蛋白免疫印迹(Western blot)法检测细胞色素-C(Cyt-C)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、B细胞白血病淋巴瘤-2相关x蛋白(Bax)和B细胞白血病/淋巴瘤2(Bcl-2)蛋白表达。结果:与正常对照组的心肌细胞比较,N-CM组心肌细胞MMP、ROS、Cyt-C蛋白表达及凋亡无明显变化(P0.05);与N-CM组比较,H-CM组心肌细胞MMP降低,ROS生成增加,凋亡增加,Cyt-C、Caspase-3和Bax蛋白表达上调(P均0.01),Bcl-2蛋白表达下调(P0.01);与H-CM组比较,T-CM组细胞MMP升高,ROS生成减少,凋亡减少,Cyt-C、Caspase-3和Bax蛋白表达下调(P0.05,P0.01),Bcl-2蛋白表达上调(P0.01)。结论:损伤的心肌微血管内皮细胞条件培养液可诱导心肌细胞凋亡,通心络可抑制该过程。     

调控自噬对H9c2心肌细胞缺氧／复氧损伤的影响

目的探讨调控自噬水平对H9c2心肌细胞缺氧／复氧（H／R）损伤的影响及意义。方法将H9c2心肌细胞缺氧2h／复氧4h,建立H／R损伤模型。以3-甲基腺嘌呤（3-MA）为自噬特异抑制剂和雷帕霉素为自噬增强剂,试验随机分为四组：正常对照组（C组）、H／R组、H／R＋100mol／L3-MA组（M＋H／R组）、H／R＋100nmol／L雷帕霉素（R＋H／R组）,应用MTT法检测细胞活力,透射电镜检测心肌细胞自噬小体,流式细胞技术检测细胞凋亡比例,Westernblot法检测自噬相关蛋白LC3、Beclin1,凋亡相关蛋白Bcl-2、Bax及下游活性片段Caspase-9、Caspase-3蛋白表达。结果H／R组明显诱导H9c2心肌细胞自噬发生、细胞活力下降、凋亡增加（P〈O．01）．Westernblot检测发现,Bax、Caspase-9、Caspase-3活性片段蛋白表达明显增加,Bcl-2表达明显抑制,Bax／Bcl-2比值、活化蛋白Caspase-3、Caspase-9表达增加（P〈O．01）;M＋H／R组H／R损伤作用明显减弱,线粒体凋亡通路及下游蛋白表达抑制（P〈O．01）;而R＋H／R组线粒体凋亡通路进一步激活,促进细胞凋亡发生（P〈O．01）。结论自噬在H9c2心肌细胞H／R损伤中起到致命性作用,抑制自噬可保护心肌细胞H,R氧化应激损伤,其机制与抑制线粒体凋亡通路有关。     

Increased glucose turnover and glucose cycling in acromegalic patients with normal glucose tolerance

Summary To characterize the diabetogenic effects of growth hormone, we simultaneously measured glucose turnover with 2-³H- and 6-³H-glucose in six acromegalic patients with normal fasting blood glucose and oral glucose tolerance tests. Eight healthy volunteers served as controls. All subjects were studied under both basal conditions and during glucose infusion (2 mg · kg^–1 · min^–1). We determined true glucose production and irreversible glucose uptake using 6-³H-glucose and glucose cycling (difference between 2-³H- and 6-³H-glucose). After an overnight fast, glucose production was higher than normal in the acromegalic patients (2.18±0.15 vs 1.85±0.03 mg · kg^–1 · min^–1,p < 0.05) despite hyperinsulinaemia. The metabolic clearance rate was normal. During the glucose infusion, glucose production was not suppressed as effectively in the acromegalic patients as in controls nor was glucose uptake augmented, while metabolic clearance rate was decreased. In acromegaly, basal glucose cycling was increased (0.44 ± 0.08 vs 0.25 ± 0.07 mg · kg^–1 · min^–1, p < 0.05). Furthermore cycling of endogenous glucose measured during glucose infusion was also augmented (0.41 ± 0.05 vs 0.24 ± 0.05 mg · kg^–1 · min^–1, p < 0.05). Hence the increase of glucose cycling (70%) was much more pronounced than that of glucose production (17%). In conclusion, small defects in glucose metabolism in acromegaly can be detected with sensitive tracer methods. These derangements are confined to the liver under fasting conditions, but are of both hepatic and extrahepatic origin during glucose loading.     

Review of glucose oxidases and glucose dehydrogenases: a bird's eye view of glucose sensing enzymes

The evolution from first-generation through third-generation glucose sensors has witnessed the appearance of a number of very diverse oxidoreductases, which vary tremendously in terms of origin, structure, substrate specificity, cofactor used as primary electron acceptor, and acceptable final electron acceptor. This article summarizes our present knowledge of redox enzymes currently utilized in commercially available glucose monitoring systems to promote a fuller appreciation of enzymatic properties and principles employed in blood glucose monitoring to help avoid potential errors.     

血糖及其他体液葡萄糖测定进展

本文从糖尿病医患角度介绍血糖测定的进展。主要从血浆糖测定到毛细血管全血糖测定，以及近年的微创组织液糖测定及无创糖测定。较详细地讨论了毛细血管全血糖测定的特点和误差的原因。     

Impaired fasting glucose and impaired glucose tolerance in urban population in India.

AIMS: To study prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in urban Indians and their demographic and anthropometric characteristics. METHODS: Data on capillary blood glucose (OGTT), anthropometric and demography details were available in 10 025 subjects (M : F 4711 : 5314) aged > or = 20 years. Glucose tolerance was categorized as normal, isolated IFG, isolated IGT, IFG + IGT and diabetes using the fasting and 2-h blood glucose (2hBG; 75-g glucose load) values. Subjects with known diabetes were excluded. RESULTS: Age-standardized prevalences of IFG, IGT and newly detected diabetes were 8.7%, 8.1% and 13.9%, respectively. IFG was more prevalent in women (9.8%) than in men (7.4%) (chi2 = 13.62, P = 0.0002), while the gender differences in IGT (men 8.4%, women 7.9%) and diabetes (men 13.3%, women 14.3%) were not significant. Body mass index and waist circumference were higher in glucose-intolerant groups than in normal glucose tolerance (NGT). Prevalence of diabetes, IGT and IFG + IGT increased with age. Among the IFG, 4% had diabetes and 27.1% had IGT using 2hBG criteria. In IFG, the fasting and 2hBG values were not correlated. CONCLUSIONS: Prevalences of IFG and IGT were similar in urban Indians and an overlap occurred in only less than half of these subjects. IFG was more common in women. Subjects with IFG were older and had more adverse anthropometric characteristics in comparison with NGT. IFG did not show an increasing trend with age.     

糖化血红蛋白与糖调节受损血糖水平相关性的研究

目的 探讨研究糖化血红蛋白(HbAlc)与糖调节受损血糖水平的相关性.方法 2009年2-3月在兰州大学附属白银医院在岗职工中开展口服75 g葡萄糖耐量试验(OGTT)和HbAlc普查,测定空腹血糖、服糖后2 h血糖及HbAlc,采用葡萄糖氧化酶法测定静脉血浆血糖,采用高效液相色谱分析法测定HbAlc.研究资料纳入标准:空腹血糖<7.0 mmol/L且服糖后2 h血糖<11.1mmol/L者,无糖尿病、血红蛋白病、肝、肾疾患等.进入结果分析的对象共726例,男197例,女529例,平均年龄(39±10)岁.其中正常糖耐量636例(87.6%),糖调节受损90例(12.4%),糖调节受损诊断采用1999年世界卫生组织糖尿病诊断标准.率间比较采用χ~2检验,双变量分析采用Pearson相关分析.结果 (1)糖调节受损占HbAlc≤5.7%人群的2.3%,占HbAlc≥5.8%的人群中89.3%.HbAlc≥5.8%时预测OGTT诊断的糖调节受损状态的敏感度、特异度、阳性预测值、阴性预测值分别为83%、99%、0.89和0.98;(2)OGTT诊断的空腹血糖受损、糖耐量减低及糖调节受损状态的患病率,在HbAlc为5.8%组与5.7%组比较差异具有统计学意义(χ~2值分别为10.077、22.219和27.780,P<0.01或P<0.001);(3)HbAlc水平与空腹血糖受损、糖耐量减低、糖调节受损的患病率之间呈显著性正相关(r值分别为0.957、0.928和0.936,均P<0.01).结论 (1)HbAlc预测糖调节受损与OGTT具有一致性,与OGTT诊断的糖调节受损状态相关的HbAlc最佳临界值为5.8%;(2)HbAlc与OGTT诊断空腹血糖受损、糖耐量减低、糖调节受损状态的血糖水平呈显著性正相关,且HbAlc为5.8%与其相关性极其密切.建议当HbAlc≥5.8%时均应行OGTY检查,以明确有无糖调节受损.     

Bioluminescence imaging of glucose in tissue surrounding polyurethane and glucose sensor implants

Background

The bioluminescence technique was used to quantify the local glucose concentration in the tissue surrounding subcutaneously implanted polyurethane material and surrounding glucose sensors. In addition, some implants were coated with a single layer of adipose-derived stromal cells (ASCs) because these cells improve the wound-healing response around biomaterials.

Methods

Control and ASC-coated implants were implanted subcutaneously in rats for 1 or 8 weeks (polyurethane) or for 1 week only (glucose sensors). Tissue biopsies adjacent to the implant were immediately frozen at the time of explant. Cryosections were assayed for glucose concentration profile using the bioluminescence technique.

Results

For the polyurethane samples, no significant differences in glucose concentration within 100 μm of the implant surface were found between bare and ASC-coated implants at 1 or 8 weeks. A glucose concentration gradient was demonstrated around the glucose sensors. For all sensors, the minimum glucose concentration of approximately 4 mM was found at the implant surface and increased with distance from the sensor surface until the glucose concentration peaked at approximately 7 mM at 100 μm. Then the glucose concentration decreased to 5.5–6.5 mM more than 100 μmm from the surface.

Conclusions

The ASC attachment to polyurethane and to glucose sensors did not change the glucose profiles in the tissue surrounding the implants. Although most glucose sensors incorporate a diffusion barrier to reduce the gradient of glucose and oxygen in the tissue, it is typically assumed that there is no steep glucose gradient around the sensors. However, a glucose gradient was observed around the sensors. A more complete understanding of glucose transport and concentration gradients around sensors is critical.     

空腹和餐后手指末梢血糖与静脉血糖浓度差异的比较分析

目的分析比较空腹和餐后2h手指末梢全血、血浆与静脉全血、血浆4种不同血样葡萄糖浓度之间的差异。方法2010年8月至12月共140例1型或2型糖尿病患者纳入试验。其中男56例、女84例,年龄（54±10）岁。空腹血糖82例．餐后2h血糖58例,每例患者采集手指末梢全血、血浆以及静脉全血、血浆4种血样。用OneTouchVerio血糖监测系统和YSI2300葡萄糖测定仪,分别检测末梢血血糖（CBG）、静脉血糖（VBG）与末梢血浆血糖（CPG）、静脉血浆血糖（VPG）。并对Verio血糖监测系统的精准性进行评估。血糖数值差异分析采用配对t检验法。结果Verio血糖监测系统的精准性符合IS015197（2003）标准要求。空腹状态下血糖仪检测的CBG与VBG分别为（6．7±2．4）、（6．7±2．3）mmol／L,相对误差为0．40％（t=0．62,P〉0．05）,YSI检测的CPG与VPG分别为（6．4±2．5）、（6．4±2．4）mmol／L,相对误差为0．25（t=0．39,P〉0．05）,CBG略高于VPG5．89％（P〈0．05）;餐后2hCBG明显高于VBG,分别为（8．5±3．6）、（7．9±3．6）mmol／L,相对误差为7．58％（t=9．55,P〈0．05）;CPG亦明显高于VPG水平,分别为（8．1±3．8）、（7．6±3．8）mmol／L,相对误差为6．08％（t=10．9,P〈0．05）,CBG高于VPG11．6％（P〈0．05）。结论OneTouchVerio血糖监测系统适合临床对患者进行日常血糖检测,其检测的空腹CBG与VPG值较为接近,餐后CBG高于VPG值。     

不同糖代谢水平动态血糖谱的差异

目的研究不同糖代谢水平血糖谱差异,以便指导干预时机的选择。方法对糖耐量正常（NGT）、空腹血糖受损（IFG）、餐后血糖受损（IGT）、IFG＋IGT及新诊断T2DM患者的72小时动态血糖监测血糖谱进行分析。结果IFG＋IGT组血糖水平及血糖漂移显著高于NGT、IFG、IGT组（P〈0．05）。新诊断T2DM组血糖水平显著高于NGT、IFG、IGT、IFG＋IGT组（P均〈0．05）。新诊断T2DM组餐后及日内血糖漂移与IFG＋IGT组无显著差异（P〉0．05）。结论（1）随着糖代谢异常的加重,血糖水平升高,血糖漂移程度增加;（2）IFG＋IGT阶段应积极干预。     

Postchallenge glucose rises with increasing age even when glucose tolerance is normal.

AIMS: Ageing increases the likelihood of developing diabetes, with associated cardiovascular disease. In a cross-sectional study, we sought to determine whether age is associated with an increase in glucose concentrations 1 h after an oral glucose challenge (1-h OGTT), even when glucose tolerance is normal (NGT). METHODS: Among subjects in the NHANES II database, 2591 subjects with NGT and documented 1-h OGTT glucose concentrations were studied. The relationship between age and 1-h OGTT glucose concentrations was assessed in a multivariable linear regression analysis. RESULTS: In a multivariable linear regression analysis, each 10-year increase in age conferred an additional 0.20 mmol/l increase in the 1-h OGTT glucose (P < 0.0001). Moreover, an interaction between age and gender was found such that 1-h OGTT glucose concentrations rose more rapidly with increasing age in men than in women. The impact of age on 1-h OGTT glucose was independent of both fasting and 2-h OGTT glucose concentrations. CONCLUSIONS: One-hour OGTT glucose concentrations rise significantly with age even in subjects with NGT. Further investigation is warranted to explore the pathophysiological significance of such age-related impairment of glucose handling, which might increase the risk of cardiovascular disease even when patients do not meet criteria for the diagnosis of diabetes or prediabetes.     

Accuracy of point-of-care glucose measurements

Control of blood glucose (BG) in an acceptable range is a major therapy target for diabetes patients in both the hospital and outpatient environments. This review focuses on the state of point-of-care (POC) glucose monitoring and the accuracy of the measurement devices. The accuracy of the POC glucose monitor depends on device methodology and other factors, including sample source and collection and patient characteristics. Patient parameters capable of influencing measurements include variations in pH, blood oxygen, hematocrit, changes in microcirculation, and vasopressor therapy. These elements alone or when combined can significantly impact BG measurement accuracy with POC glucose monitoring devices (POCGMDs). In general, currently available POCGMDs exhibit the greatest accuracy within the range of physiological glucose levels but become less reliable at the lower and higher ranges of BG levels. This issue raises serious safety concerns and the importance of understanding the limitations of POCGMDs. This review will discuss potential interferences and shortcomings of the current POCGMDs and stress when these may impact the reliability of POCGMDs for clinical decision-making.