清醒大鼠急性高血糖模型的建立及其“肾毒性”损伤特点及机制研究

目的 建立大鼠清醒状态下急性高血糖模型,观察急性高血糖引起肾损伤的特点,并探讨其可能机制.方法 应用随机数字表法将Sprague-Dawley大鼠分为高糖组和对照组(n=10),颈静脉置管术后行高葡萄糖钳夹实验建立急性高血糖模型.术后第5天高糖组经颈静脉置管泵入50％葡萄糖溶液,使血糖维持于16 ～ 18 mmol/L;对照组以同等速度泵入生理盐水,实验持续6h,留取24 h尿液后处死大鼠并取材.光镜和透射电镜观察肾脏结构损伤,检测肾功能、尿微量白蛋白(UMA)及肾损伤分子-1(KIM-1)等肾损伤指标,检测超氧化物歧化酶(SOD)、丙二醛及8-羟基-2'-脱氧鸟苷(8-OHdG)评估氧化应激水平.结果 高糖组出现明显肾脏结构和功能损伤.结构上可见近曲小管细胞肿胀,细胞内线粒体肿胀、排列紊乱;与对照组相比,高糖组24 h UMA、KIM-1及中性粒细胞明胶酶相关载脂蛋白(NGAL)均显著升高(t=-2.969、-2.220、-2.791,P均＜0.05),而血清及肾组织SOD活性明显下降(t=2.537、2.599,P均＜0.05),血清丙二醛、肾组织丙二醛及尿8-OHdG明显升高(t=-2.532、-2.600、-2.968,P均＜0.05).结论 成功建立大鼠急性高血糖模型.急性高血糖可导致肾脏结构和功能损伤,以肾小管损伤为主,氧化应激及线粒体损伤参与急性高血糖“肾毒性”损伤的发生、发展.     

女性肥胖和2型糖尿病患者高葡萄糖钳夹过程中胰岛素原的分泌和释放

目的 探讨女性肥胖和2型糖尿病患者在持续高糖情况下胰岛素原分泌和释放的变化.方法 12例肥胖、7例2型糖尿病和9例正常对照组,行150分钟高葡萄糖钳夹试验,用酶联免疫法测定各时点胰岛素原.结果 肥胖组和2型糖尿病组空腹胰岛素原(PI)水平高于对照组.2型糖尿病组在10～150分钟期间胰岛素原/胰岛素比值高于肥胖组和对照组.Spearman相关分析显示,PI与胰岛素原分泌第一时相(FPPR)(r=0.464,P=0.026)和内脏脂肪(VA)(r=0.447,P=0.033)呈正相关;与葡萄糖代谢清除率(GDR)(r=-0.533,P=0.009)呈负相关.结论 胰岛素原分泌与胰岛素抵抗密切相关.持续高糖情况下肥胖患者由于胰岛素抵抗代偿性高分泌胰岛素原,2型糖尿病患者存在胰岛功能损害,胰岛素原分泌降低,而且胰岛素原转换胰岛素过程中存在缺陷.     

急性生理与慢性健康状况评分Ⅱ在老年高渗性高血糖状态患者中的应用

目的 探讨急性生理与慢性健康状况评分(APACHE)Ⅱ对糖尿病高渗性高血糖状态患者病情评价和治疗预后的价值. 方法 2003年1月至2008年5月,在本院急诊抢救室治疗的糖尿病高渗性高血糖状态患者在入院当天进行治疗前APACHE Ⅱ评分,根据患者预后分为死亡组和存活组,对两组APACHEⅡ评分进行比较.应用Logistic回归分析评价死亡的危险因素. 结果 40例患者入选,死亡10例,存活30例,病死率为25%.治疗前两组患者血糖、血钠、血渗透压、血肌酐和血红蛋白差异无统计学意义(t=-1.50～1.53,P>0.05).入院当天治疗前死亡组APACHE Ⅱ评分分值明显高于存活组,分别为(30.1±5.4)分和(22.9±3.9)分(Z=-4.08,P<0.01);Logistic回归分析显示,入院当天治疗前APACHEⅡ分值是死亡独立危险因素,年龄、性别、血糖、有效血渗透压、血肌酐和血红蛋白不是死亡危险因素. 结论 APACHEⅡ评分有助于评价糖尿病高渗性高血糖状态患者的病情和预后.     

Evidence-based management of hyperglycemic emergencies in diabetes mellitus

The hyperglycemic emergencies, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are potentially fatal complications of uncontrolled diabetes mellitus. The incidence of DKA and the economic burden of its treatment continue to rise, but its associated mortality rate which was uniformly high has diminished remarkably over the years. This Improvement in outcome is largely due to better understanding of the pathogenesis of hyperglycemic emergencies and the application of evidence-based guidelines in the treatment of patients. In this article, we present a critical review of the evidence behind the recommendations that have resulted in the improved prognosis of patients with hyperglycemic crises. A succinct discussion of the pathophysiology and important etiological factors in DKA and HHS are provided as a prerequisite for understanding the rationale for the effective therapeutic maneuvers employed in these acute severe metabolic conditions. The evidence for the role of preventive measures in DKA and HHS is also discussed. The unanswered questions and future research needs are also highlighted.     

极化液治疗危重患儿高糖性高渗血症临床分析

目的探讨极化液治疗危重患儿高糖性高渗血症的疗效。方法将高糖性高渗血症患儿35例随机分为极化液治疗组18例和对照组17例。在综合治疗基础上,治疗组予极化液降糖治疗,监测两组患儿治疗前、入院8～12h、第2,3天血糖。同时应用简化小儿危重病例评分法进行病情评估。结果入院时、入院8—12h、第2天血糖值,治疗组血糖下降较快,两组比较差异有统计学意义（P〈0．01）,第3天两组血糖下降比较差异无统计学意义（P〉0．05）。第2天治疗组转安率78％,对照组转安率41％,两组转安率比较差异有统计学意义（P〈0．05）;第3天两组转安率分别为100％、78％,两组比较差异无统计学意义（P〉0．05）。结论应用极化液治疗危重患儿高糖性高渗血症安全有效、经济简便,利于疾病恢复.     

左旋门冬酰胺酶致急性淋巴细胞白血病患儿发生高血糖的护理

左旋门冬酰胺酶（L-Asp）是目前治疗急性淋巴细胞白血病（ALL）联合化疗（VDLP）中的主要药物之一。它能使患儿的完全缓解率和生存率明显提高。但是该药在使用的过程中往往会产生一些较为突出的不良反应,     

Hippocampal injury and neurobehavioral deficits are improved by PD 81,723 following hyperglycemic cerebral ischemia

We investigated the effects of PD 81,723, an allosteric enhancer for the adenosine A(1) receptor subtype, on hippocampal injury and Morris water maze (MWM) performance following hyperglycemic cerebral ischemia and reperfusion (4-VO, 10 min) in the rat. PD 81,723 (3 or 10 mg/kg) or the equivalent volume of saline was administered intraperitoneally 30 min prior to ischemia. Moderate hyperglycemia was achieved by administration of D-glucose (3g/kg, i.p.) 15 min prior to induction of ischemia. Morris water maze trials were performed on the 6th, 7th, and 8th days after the ischemic insult. The rat brains were sectioned (8 microm), stained with cresyl violet/acid fuchsin, and evaluated for hippocampal ischemic injury by an experimenter blinded to the treatment conditions. At the higher dose, PD 81,723 (10 mg/kg) had no effect on hippocampal injury or MWM performance following hyperglycemic ischemia compared to corresponding saline-treated animals. In contrast, a lower dose of PD 81,723 (3 mg/kg) resulted in significant (P < 0.05, n = 8) reduction of hippocampal injury following hyperglycemic ischemia. Furthermore, corresponding Morris water maze performance (latency, learning index, and cumulative distance swum) was significantly improved by PD 81,723 (P < 0.05, n = 8). The results of the present study suggest that, in the presence of PD 81,723, an A(1) allosteric enhancer, endogenously produced adenosine is sufficient to exert significant neuroprotection during hyperglycemic ischemia. Moreover, the present study provides further evidence for a neuromodulatory role of adenosine during hyperglycemic ischemia.     

太白楤木总皂苷对糖尿病小鼠血糖血脂及抗氧化作用的影响

目的观察太白楤木总皂苷对四氧嘧啶糖尿病小鼠血糖、血脂的调节作用。方法将小鼠随机分为正常组、模型组、二甲双胍组及太白楤木总皂苷（total saponin of Aralia taibaiensis,SAT）30、60、120mg·kg^-1剂量组,连续4周灌胃给药,末次给药后尾静脉取血测定血糖、血脂指标;分离肝组织测定抗氧化指标。结果太白楤木总皂苷60、120mg·kg^-1剂量组可显著降低四氧嘧啶糖尿病小鼠的血糖（P〈0．01）,且以高剂量120mg·kg^-1的降糖作用最明显。4周治疗结束后,上述两剂量组的血清中总胆固醇（TC）、甘油三酯（TG）、游离脂肪酸（FFA）和丙二醛（MDA）含量显著降低（P〈0．01或P〈0．05）,胰岛素含量、高密度脂蛋白（HDL-c）含量、过氧化物酶（SOD）及及胰岛素敏感指数（ISI）显著升高（P〈0．05或P〈0．01）,但低密度脂蛋白（LDL-c）含量变化不明显（P〉0．05）。在太白楤木总皂苷的剂量为120mg·kg^-1时,其降血糖、降血脂及其抗氧化效果同二甲双胍相当（P〉0．05）。结论太白楤木总皂苷可降低糖尿病小鼠的血糖,其降糖机制可能与其提高糖尿病小鼠抗氧化能力,改善血脂代谢紊乱,提高肝脏及外周组织胰岛素敏感性,改善胰岛素抵抗有关。