红细胞山梨醇水平与糖尿病患者糖代谢控制

采用山梨醇脱氢酶法测定了正常人23例及糖尿病66例的红细胞山梨醇水平。发现血糖控制差的Ⅰ型及Ⅱ型糖尿病的红细胞山梨醇水平显著高于正常对照组,且与同时测定的空腹血糖、24小时尿糖以及HbAic之间存在着显著的正相关;血糖控制好的Ⅱ型糖尿病组的红细胞山梨醇水平与正常对照组无显著差异且与空腹血糖不相关;血糖控制差的Ⅰ型与Ⅱ型糖尿病组之间空腹血糖差异无显著性,但红细胞山梨醇水平差异却有显著性。提示红细胞山梨醇水平可以作为糖尿病患者糖代谢控制好坏的一个指标。     

参麦活血饮对糖尿病大鼠坐骨神经和红细胞山梨醇水平及神经功能的影响

目的 探讨糖尿病（DM）大鼠坐骨神经和红细胞山梨醇含量与神经功能之间的关系。观察参麦活血饮进行短期干预的作用和可能机制。方法 采用链脲佐菌素诱发DM大鼠模型。造模1周后用中成药参麦活血饮（成分为红参，麦冬，红花）治疗。用药4周后测定神经电生理，坐骨神经和红细胞山梨醇水平。结果 DM大鼠神经传导速度减慢，坐骨神经和红细胞山梨醇水平升高；经参麦活血饮治疗后上述改变减轻。同时，红细胞和坐骨神经山梨醇水平呈正相关；感觉神经传导速度与坐骨神经和红细胞山梨醇水平呈负相关，H反射与坐骨神经和红细胞山梨醇水平呈正相关。运动神经传导速度与坐骨神经和红细胞山梨醇水平无明显相关。结论 DM时红细胞山梨醇水平可反映坐骨神经山梨醇水平，亦能反映周围神经的病变程度，中药参麦活血饮可明显缓解DM大鼠周围神经的早期病变。     

醛糖还原酶抑制剂对实验性糖尿病大鼠周围神经病变的影响

从60只Wistar大鼠中随机取45只用链脲佐菌素制备糖尿病大鼠模型,共成模35只,随机分为糖尿病对照组(DC组)18只和糖尿病水飞蓟素治疗组(DT组)17只,余15只作为正常对照组(NC).实验结束前测定大鼠运动神经传导速度、红细胞山梨醇含量及血小板聚集率,并进行坐骨神经形态学检查.结果有醛糖还原酶抑制活性的中药提取物水飞蓟素明显降低了DT组大鼠红细胞山梨醇含量,部分显著改善了运动或感觉神经传导速度和血小板聚集率,并改善了神经结构异常.认为水飞蓟素对糖尿病神经病变有防治作用.     

糖尿病大鼠红细胞山梨醇与晶体,坐骨神经山梨醇含量的相关性

近年来的研究发现,山梨醇在一些组织中的异常增高是引起糖尿病白内障、神经病变等慢性并发症的重要原因之一。红细胞山梨醇含量已广泛用于糖尿病慢性并发症的研究。我们探讨了大鼠红细胞山梨醇含量与晶体和坐骨神经山梨醇含量间的关系。 一、材料与方法     

水飞蓟素对糖尿病大鼠周围神经病变的影响

目的　观察水飞蓟素对糖尿病大鼠红细胞山梨醇含量、坐骨神经功能及血小板聚集的影响。　方法　自 60只Wistar大鼠中随机抽取 45只 ,链脲佐菌素制备糖尿病大鼠模型 ,将成模大鼠随机分为糖尿病对照组 (DC组 ,n =18)和糖尿病治疗组 (DT组 ,n =17) ,余 15只作为正常对照组(NC) ,实验结束前测定运动神经传导速度、红细胞山梨醇含量及血小板聚集率。　结果　水飞蓟素明显降低了DT组大鼠红细胞山梨醇含量 (52± 6vs 98± 9,DTvsDC ,P <0 .0 1) ,显著改善了运动神经传导速度和血小板聚集率 (P均 <0 .0 5)。　结论　水飞蓟素通过纠正神经组织代谢紊乱、改善血液流变学和减轻神经内膜缺血对糖尿病神经病变起防治作用     

糖尿病大鼠神经功能和神经山梨醇的变化及黄腐酸钠的 …

目的 观察实验性糖尿病大鼠的神经功能与神经山梨醇变化及中药黄腐酸钠对其影响。方法 腹腔注射链脲佐菌素建立糖尿病大鼠模型。给邓黄腐酸钠防治６个月后,测定大鼠的血糖、糖化血红蛋白、神经山梨醇含量,利用热痛测试仪及热板试验测定痛阈变化。结果 （１）黄腐酸钠治疗未显示降血糖作用。（２）糖尿病非治疗组热痛缩腿反应潜伏期（６．４３０．４８）稍明显缩短,热板试验显示在非伤害性温度下（４０℃）即出现痛觉反应,４４     

筋脉通对糖尿病大鼠坐骨神经传导速度、醛糖还原酶及山梨醇浓度的影响

目的观察中药复方筋脉通对糖尿病大鼠坐骨神经传导速度、坐骨神经组织和红细胞内醛糖还原酶活性(AR)及山梨醇(SNS)浓度的影响,并探讨其作用机理。方法采用链脲佐菌素(STZ)糖尿病(DM)大鼠模型,给予中药复方筋脉通灌胃,并以氨基胍为对照,疗程8周。观察该制剂对糖尿病大鼠坐骨神经传导速度、坐骨神经组织和红细胞醛糖还原酶活性(AR)及对山梨醇(SNS)浓度的影响。结果经筋脉通治疗后,糖尿病大鼠坐骨神经传导速度增快,坐骨神经和红细胞SNS浓度、坐骨神经AR明显降低,和对照组比较有显著性差异(P<0.05～0.01)。红细胞内AR有降低的趋势,但无统计学意义。对血糖有下降作用。结论提示筋脉通对改善糖尿病神经病变有一定的疗效。     

抗坏血酸对NIDDM患者红细胞山梨醇的影响

对２７例ＮＩＤＤＭ患者血浆抗坏血酸及红细胞山梨醇含量进行了测定，并观察了口服抗坏血酸对ＮＩＤＤＭ患者红细胞山梨醇的影响。提示ＮＩＤＤＭ患者抗坏血酸代谢紊乱是造成山梨醇在一些组织异常增高的原因之一，补充抗坏血酸有助于纠正ＮＩＤＤＭ患者多元醇代谢的异常。     

2型糖尿病周围神经病变患者尿山梨醇排泄的变化

目的探讨2型糖尿病患者尿山梨醇与周围神经病变（DPN）的关系。方法采用固相夹心酶联免疫吸附法测定63例2型糖尿病患者（无DPN组）,134例2型糖尿病周围神经病变患者（DPN组）和72例正常对照组的24h尿山梨醇排泄量,并分析其与病程、血糖、糖化血红蛋白、血清胰岛素、甘油三酯、总胆固醇、尿白蛋白排泄率（UAER）和神经传导速度的关系。结果2型糖尿病DPN患者尿山梨醇水平高于无DPN组和正常对照组（P〈0．05或〈0．01）;2型糖尿病患者尿山梨醇水平与神经传导速度呈负相关,与病程和UAER（P〈0．05或〈0．01）呈正相关。结论尿山梨醇可作为2型糖尿病周围神经病变的检测指标。     

血糖波动与糖尿病周围神经病变的相关性

目的 探讨血糖波动与糖尿病周围神经病变（DPN）严重程度的相关性. 方法 选取DPN患者126例,根据多伦多神经病变评分分为轻、中、重度组.所有患者均采用动态血糖监测系统（CGMS）监测72 h,计算平均血糖水平（MBG）、日内平均血糖波动幅度（MAGE）、血糖波动最大幅度（DMMG）、血糖标准差（SD）,并记录年龄、性别、病程、BMI、HbA1c及一般生化指标. 结果 MBG、MAGE、SD随着神经病变严重程度的增加而增加（P＜0.05）,神经病变严重程度分别与MBG、MAGE呈正相关（β=0.249、0.196,P＜0.05）. 结论 T2DM患者血糖波动可能与DPN严重程度相关.     

Effect of a new aldose reductase inhibitor, 8'-chloro-2',3'-dihydrospiro [pyrrolidine-3,6'(5'H)-pyrrolo[1,2,3-de] [1,4]benzoxazine]-2,5,5'- trione (ADN-138), on delayed motor nerve conduction velocity in streptozotocin-diabetic rats

The effects of a chemically new type of aldose reductase inhibitor, ADN-138, on delayed motor nerve conduction velocity (MNCV) and sciatic nerve sorbitol, fructose and myo-inositol levels were studied in streptozotocin-diabetic rats. MNCV in rats was significantly delayed after 3 weeks of diabetes and ADN-138 treatment was started at this point. Treatment of diabetics with ADN-138 at 5 and 20 but not 1 mg/kg/d for 3 weeks resulted in a significant increase in MNCV and reduced sorbitol levels to or below those of nondiabetic controls. However, fructose, though decreased in a dose-dependent manner, was not normalized. The reference drug, Sorbinil, showed similar effects on them. After the 3 weeks of ADN-138(20 mg/kg/d) treatment, diabetics were left on ADN-138 or continued further to be treated with it for 3 weeks. The withdrawal of ADN-138 prevented a further increase in MNCV and restored sorbitol and fructose to nontreated diabetic levels, and myo-inositol levels declined. In contrast, the ADN-138-continued group kept improving its MNCV and normalized sorbitol and myo-inositol. These results suggest that polyol accumulation is responsible for delayed MNCV and that the action of ADN-138 on MNCV reflected reversibility of metabolic function in diabetics.     

复方丹参片对糖尿病大鼠坐骨神经和红细胞山梨醇浓度的影响

目的观察复方丹参片对糖尿病（DM）大鼠周围神经病变的防治作用，并分析其作用机制。方法采用链脲佐菌素诱发DM大鼠模型。造模1w后开始用不同剂量的复方丹参片进行治疗。用药4W后观察各组大鼠血檐（FBG）、糖化血清蛋白（GSP）、体重（w）、坐骨神经山梨醇、红细胞山梨醇（RBCS）含量的变化，同时测定大鼠坐骨神经传导速度。结果复方丹参片能降低DM大鼠GSP、坐骨神经和RBcs含量，增加坐骨神经传导速度。结论复方丹参片对DM大鼠周围神经病变有防治作用。     

肝硬化患者红细胞免疫功能与脂质过氧化关系的研究

探讨肝硬化患者红细胞免疫功能的变化及其与脂质过氧化的关系。应用红细胞酵母菌花环法测定红细胞免疫功能 ,并采用化学比色法测定血浆丙二醛 (MDA)、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH -Px)含量。其中肝硬化患者 31例 ,健康对照 30例。肝硬化组RBC -IC花环率明显提高 ,P <0 .0 5 ;而RBC -C3b受体花环率与正常人无显著性差异 (P >0 .0 5 )。肝硬化组SOD、GSH -Px、SOD/MDA低于正常 (P <0 .0 1) ;而MDA明显高于正常 (P <0 .0 1)。线性相关分析显示 ,RBC -C3b花环率与MDA呈显著负相关 (r= 0 .42 3,P <0 .0 5 )。RBC -ICR与MDA明显正相关 (r=0 .5 2 3,P <0 .0 5 )。肝硬化患者红细胞免疫粘附功能降低 ,与活性氧代谢紊乱密切相关     

血清神经生长因子在糖尿病性周围神经病变发病中的作用

目的 探讨神经生长因子(NGF)在糖尿病性周围神经病变(DNP)发病机制中的作用及其与感觉神经传导速度(SNCV)的相关性. 方法 41名临床确诊为DNP的患者、35名患糖尿病但无DNP的患者及33名健康对照者应用酶联免疫吸附法测量血清NGF水平及左侧正中神经、尺神经、腓神经和胫神经SNCV,进行相关分析. 结果 DNP组患者血清NGF水平为(665.18±188.32)ng/L,显著低于健康对照组(976.44±159.07)ng/L和糖尿病不伴DNP组(943.32±167.33)ng/L(F=9.316,P<0.001),DNP患者NGF水平与正中神经和腓神经SNCV之间呈正相关(r=0.810,0.760,均P<0.001),NGF水平下降程度与DNP病程之间呈正相关(r=0.542,P<0.001). 结论 DNP患者血清NGF水平低于健康者,NGF合成下降在DNP的发病机制中起一定的作用.     

The role of cyclic adenosine 3',5'-monophosphate and polyol metabolism in diabetic neuropathy.

The effects of a stable prostacyclin analog, Iloprost, and aldose reductase inhibitors (ONO-2235 and isoliquiritigenin) were studied to elucidate the role of cAMP in diabetic neuropathy in relation to polyol metabolism. In in vivo experiments, the cAMP and myoinositol contents in sciatic nerves and motor nerve conduction velocity were significantly reduced in diabetic rats. Iloprost significantly restored the reduced cAMP content in sciatic nerves and improved motor nerve conduction velocity in diabetic rats. However, the contents of sorbitol or myoinositol in sciatic nerves were not affected by Iloprost in diabetic rats. On the other hand, aldose reductase inhibitors significantly reduced the sorbitol content and increased the cAMP and myoinositol contents in the sciatic nerves of diabetic rats. The motor nerve conduction velocity was also slightly but significantly improved by treatment with aldose reductase inhibitors. There was a negative correlation between cAMP and sorbitol in the sciatic nerves of diabetic rats treated with aldose reductase inhibitors and a positive correlation between cAMP and motor nerve conduction velocity. In in vitro experiments, Iloprost significantly increased cAMP, but did not affect the sorbitol content in sciatic nerves. Aldose reductase inhibitors inhibited sorbitol accumulation and increased cAMP in sciatic nerves. Our data suggest that polyol pathway activation somehow results in cAMP reduction in sciatic nerves and that the reduction of cAMP in peripheral nerves may be closely related to the pathogenesis of diabetic neuropathy.     

Plasma and red cell sorbitol assay in diabetic subjects

Summary Plasma and red cell sorbitol concentrations, fasting plasma glucose, glycosylated hemoglobin (GHb) were evaluated in 30 diabetic patients and 42 normal subjects. Red cell sorbitol levels were evaluated in hemolysate and non-hemolyzed samples. Mean red cell sorbitol concentrations evaluated after hemolysis were 21.5±5 nmol/ml in diabetics and 12.2±4 nmol/ml in controls (p<0.001). Mean values of red cell sorbitol determined in non-hemolyzed samples were 13.9±3 nmol/ml in diabetics and 8.1±3 nmol/ml in controls (p<0.001). Mean plasma sorbitol concentrations were 8.4±3 nmol/ml in diabetics and 5.2±1 nmol/ml in controls (p<0.001). The within and between run reproducibilities evaluated in plasma, hemolysate and non-hemolyzed red cells gave the lowest values for hemolyzed red cell samples. The studies on stability showed that samples neutralized and stored at −20°C gave reproducible values if assayed within 3 days. A positive correlation was found between red cell hemolysate sorbitol concentrations and fasting plasma levels in both diabetics (r=0.56; p<0.001) and controls (r=0.62; p<0.001). Red cell hemolysate sorbitol concentrations were also positively correlated to GHb in both diabetics (r=0.64; p<0.001) and controls (r=0.36; p<0.05). We believe the most effective sorbitol assay to be that obtained in hemolyzed red cells and that these values related to glycemic levels could be a useful index of metabolic control and an indicator of tissue sorbitol levels in humans. Supported by C.N.R. grant ‘Progetto Finalizzato Medicina Preventiva e Riabilitativa - Sottoprogetto Malattie Degenerative’.     

Erythrocytic sorbitol contents in diabetic patients correlate with blood aldose reductase protein contents and plasma glucose levels, and are normalized by the potent aldose reductase inhibitor fidarestat (SNK-860)

The accumulation of sorbitol by the activated polyol pathway is considered to be a major cause of diabetic neuropathy. Because the erythrocytic sorbitol contents reportedly reflects that in nerves, erythrocytic sorbitol measurement would be useful for confirming the effect of an aldose reductase inhibitor (ARI). In this study, we examined erythrocytic sorbitol contents in healthy subjects and diabetic patients under fasting and postprandial conditions. Then, the contributions of blood aldose reductase (AR) contents and plasma glucose levels to the accumulated erythrocytic sorbitol contents were also analyzed. Erythrocytic sorbitol contents in the healthy subjects were 11.7 and 12.5–12.6 nmol/g Hb in fasting and postprandial status, respectively. In contrast, the erythrocytic sorbitol contents in diabetic patients were apparently higher (approximately 2.5-fold), but fidarestat treatment restored the elevated erythrocytic sorbitol contents to normal. In the diabetic patients, erythrocytic sorbitol contents were highly correlated with blood AR contents multiplied by the plasma glucose levels, whereas in the normal and fidarestat-treated diabetic patients no such correlation was observed. Taken together, these results suggest both the blood AR contents and the plasma glucose levels are factors determining erythrocytic sorbitol contents in diabetic patients. Notably, the potent ARI fidarestat was shown to normalize elevated erythrocytic sorbitol contents.     

Enhanced Spontaneous Platelet Aggregation and red Blood Cell Fragility in Whole Blood Obtained from Patients with Diabetes

SUMMARY. Using a platelet counting technique, spontaneous platelet aggregation (SPA) was determined in citrated whole blood (WB) and platelet-rich plasma (PRP) obtained from 27 patients with insulin-dependent diabetes mellitus and from 32 healthy controls. SPA in WB, but not in PRP, was significantly enhanced in the patients compared with the controls. In the patient group, SPA in WB correlated positively with poor metabolic control as measured by glycosylated haemoglobin (Hb A(1)). Furthermore, the increased SPA in WB from diabetics was found to be associated with an increased mechanical fragility of red blood cells (RBC) measured as liberation of haemoglobin into the plasma in stirred samples of WB. Pentoxifylline, which is believed to increase the deformability of RBC, reduced the extent of SPA in WB from the patients but was without effect on SPA in PRP from the patients or in WB from the controls.