Effects of the sulphydryl donor N-acetyl-L-cysteine on nerve conduction, perfusion, maturation and regeneration following freeze damage in diabetic rats

Abstract. Peripheral nerve conduction velocity deficits in diabetic rats depend on decreased nerve perfusion, which may be related to increased free radical activity and impaired endogenous protection by the glutathione redox cycle. We studied the effect of treatment with the glutathione precursor N -acetyl-L-cysteine on nerve conduction, blood flow, maturation and regeneration. Two months of diabetes in mature rats caused 20% and 48% deficits in sciatic motor conduction velocity and endoneurial blood flow, respectively, which were largely corrected by N -acetyl-L-cysteine treatment during the second month. In young non-diabetic rats, sciatic motor conduction velocity increased by 31% over 6 weeks. Diabetes halved the conduction velocity maturation rate, however N -acetyl-L-cysteine treatment allowed a normal pattern of development. After 1 month of treated or untreated diabetes, the sciatic nerve was lesioned by a liquid nitrogen-cooled probe. Myelinated fibre regeneration distance, determined electrophysiologically, was reduced by 12.2% with diabetes; this was prevented by N -acetyl-L-cysteine treatment. Thus, the data stress the importance of free radical-mediated changes in the aetiology of experimental diabetic neuropathy.     

Neurovascular dysfunction in diabetic rats. Potential contribution of autoxidation and free radicals examined using transition metal chelating agents.

Oxygen free radical activity is elevated in diabetes mellitus and has been implicated in the etiology of vascular complications. Recent studies have shown that impaired perfusion of nerve endoneurium is a major cause of nerve fiber dysfunction in experimental diabetes. Free radical scavenger treatment prevents the development of nerve conduction abnormalities in diabetic rats. In vitro experiments suggest that autoxidation reactions of glucose, catalyzed by free transition metal ions, are a potential source of free radicals in diabetes. We investigated whether chronic treatment with deferoxamine and trientine, transition metal chelating agents which can prevent autoxidation, could correct nerve conduction and blood flow changes in streptozotocin-diabetic rats. A 20% reduction in sciatic nerve motor conduction velocity after 2 mo diabetes was 90% ameliorated by 2 wk of treatment with deferoxamine or trientine. Sciatic endoneurial nutritive blood flow was 45% reduced by diabetes, but was completely corrected by treatment. In contrast, transition metal chelation had no effect on blood flow or conduction velocity in nondiabetic rats. Thus, the data support the hypothesis that increased free radical activity by glucose autoxidation as a result of impaired transition metal handling is a major cause of early neurovascular deficits in diabetes.     

Glutathione and alpha-lipoate in diabetic rats: nerve function, blood flow and oxidative state

BACKGROUND: Increased oxidative stress is considered to be a causal factor in the development of diabetic complications, among which peripheral neuropathy. The pathophysiology of nerve dysfunction in diabetes has been explained both by reduced endoneurial microcirculation and alterations in endoneurial metabolism. It is unclear whether antioxidants primarily improve nerve blood flow or normalise systemic or endoneurial oxidative metabolism. Therefore, we evaluated the effects of the antioxidants glutathione and alpha-lipoic acid on both nerve microcirculation and the antioxidative capacity and lipid peroxidation in experimentally diabetic rats. MATERIALS AND METHODS: Streptozotocin-diabetic rats were treated with different doses of alpha-lipoic acid, reduced glutathione or placebo, and were compared with nondiabetic controls. We measured systemic and endoneurial antioxidants, malondialdehyde and whole blood hydrogen peroxide. Furthermore, we evaluated sciatic and tibial motor and sensory nerve conduction velocity, caudal nerve conduction velocity, and assessed sciatic nerve blood flow and vascular resistance by Laser-Doppler flowmetry. RESULTS: We observed a rise in erythrocyte glutathione by 27 % (P < 0.05), and a trend towards decreased plasma malondialdehyde in alpha-lipoic acid, but not in glutathione-treated animals in comparison with the placebo group. Simultaneously, sciatic nerve blood flow and vascular resistance were improved by daily alpha-lipoic acid administration by 38% (P < 0.05). Peripheral nerve conduction velocity and endoneurial glutathione were not significantly influenced by antioxidant treatment. CONCLUSIONS: Only minor beneficial effects of alpha-lipoic acid on nerve blood flow and oxidative state occur at the given doses; these effects were insufficient to improve nerve conduction deficits.     

Effects of insulin treatment on endoneurial and systemic oxidative stress in relation to nerve conduction in streptozotocin-diabetic rats

As increased oxidative stress is probably a pathogenetic factor in the development of diabetic complications, we studied nerve function and endogenous antioxidants in plasma, erythrocytes and sciatic nerve of untreated and insulin-treated streptozotocin-diabetic rats. After 18 weeks, the diabetes-induced sciatic nerve conduction velocity deficits were approximately 65% improved by insulin ( P <0.001). Plasma superoxide dismutase was significantly reduced in diabetes ( P <0.01); smaller decreases in plasma catalase and glutathione levels were observed. These changes were corrected by insulin treatment. In erythrocytes, decreased superoxide dismutase ( P <0.05) and increased total glutathione levels ( P <0.05) were found. All effects of diabetes, including a rise in plasma malonyldialdehyde ( P <0.05), were partially reversed by insulin treatment. In nervous tissue, diabetes caused increased catalase activity, uninfluenced by insulin ( P <0.05). Nerve superoxide dismutase and glutathione did not change. The data suggest that, in diabetes, changes in systemic rather than endoneurial oxidative stress lead to nerve dysfunction.     

Effects of the protein kinase C beta inhibitor LY333531 on neural and vascular function in rats with streptozotocin-induced diabetes

Elevated protein kinase C activity has been linked to the vascular and neural complications of diabetes. The aim of the present study was to examine the involvement of the beta-isoform of protein kinase C in abnormalities of neuronal function, neural tissue perfusion and endothelium-dependent vasodilation in diabetes, by treatment with the selective inhibitor LY333531 (10 mg.kg(-1).day(-1)). Diabetes was induced in rats by streptozotocin; the duration of diabetes was 8 weeks. Nerve conduction velocity was monitored, and responses to noxious mechanical and thermal stimuli were estimated by the Randall-Sellito and Hargreaves tests respectively. Sciatic nerve and superior cervical ganglion blood flow were measured by microelectrode polarography and hydrogen clearance. Vascular responses were examined using the in vitro mesenteric bed preparation. An 8-week period of diabetes caused deficits in sciatic motor (20%) and saphenous nerve sensory (16%) conduction velocity, which were reversed by LY333531. Diabetic rats had mechanical and thermal hyperalgesia. LY333531 treatment did not affect mechanical thresholds, but corrected thermal hyperalgesia. Sciatic nerve and superior cervical ganglion blood flow were both reduced by 50% by diabetes; this was almost completely corrected by 2 weeks of LY333531 treatment. Diabetes caused a 32% reduction in vasodilation of the mesenteric vascular bed in response to acetylcholine, mediated by nitric oxide and endothelium-derived hyperpolarizing factor. When the former was abolished during nitric oxide synthase inhibition, an 80% diabetic deficit in the remaining relaxation was noted. LY333531 treatment attenuated the development of these defects by 64% and 53% respectively. Thus protein kinase C beta contributes to the neural and vascular complications of experimental diabetes; LY333531 is a candidate for further study in clinical trials of diabetic neuropathy and vasculopathy.     

Nicotinamide reverses neurological and neurovascular deficits in streptozotocin diabetic rats

In diabetes, activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an important effector of oxidative-nitrosative injury, which contributes to the development of experimental diabetic peripheral neuropathy (DPN). However, the potential toxicity of complete PARP inhibition necessitates the utilization of weaker PARP inhibitors with additional therapeutic properties. Nicotinamide (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can improve energy status and inhibit cell death in ischemic tissues. We report the dose-dependent effects of nicotinamide in an established model of early DPN. Control and streptozotocin-diabetic rats were treated with 200 to 400 mg/kg/day nicotinamide (i.p.) for 2 weeks after 2 weeks of untreated diabetes. Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and hydrogen clearance, and sciatic motor and hind-limb digital sensory nerve conduction velocities and thermal and mechanical algesia were measured by standard electrophysiological and behavioral tests. Malondialdehyde plus 4-hydroxyalkenal concentration in the sciatic nerve and amino acid-(4)-hydroxynonenal adduct and poly(ADP-ribosyl)ated protein expression in human Schwann cells were assessed by a colorimetric method with N-methyl-2-phenyl indole and Western blot analysis, respectively. Nicotinamide corrected increased sciatic nerve lipid peroxidation in concert with nerve perfusion deficits and dose-dependently attenuated nerve conduction slowing, as well as mechanical and thermal hyperalgesia. Nicotinamide (25 mM) prevented high (30 mM) glucose-induced overexpression of amino acid-(4)-hydroxynonenal adducts and poly(ADP-ribosyl)ated proteins in human Schwann cells. In conclusion, nicotinamide deserves consideration as an attractive, nontoxic therapy for the treatment of DPN.     

2型糖尿病患者糖尿病周围神经病变相关因素分析

目的 探讨2型糖尿病患者糖尿病周围神经病变(DPN)相关因素。方法 选择2型糖尿病患者114例,根据肌电图中运动及感觉神经传导速度,评估糖尿病周神经病变情况,分为DPN组73例和非糖尿病周围神经病变(NDPN)组41例,分别就其性别、年龄、病程、体重指数、腰围、空腹血糖、餐后血糖、糖化血红蛋白(HbA1c)、血脂、运动及感觉神经传导速度、颈动脉内中膜厚度、足部踝肱指数、感觉阈值等指标进行分析。 结果 DPN 组年龄、病程、空腹及餐后血糖、HbA1c均高于NDPN组(P<0.05),运动及感觉神经传导速度低于NDPN组(P<0.01),颈动脉内中膜厚度、足部感觉振动阈值高于NDPN组(P<0.05)。结果表明,高龄、病程长、高HbA1c水平是2型糖尿病患者发生DPN的独立危险因素(P<0.05)。 结论 2型糖尿病患者DPN的发生与年龄、病程、HbA1c水平有关。     

Reversal of experimental diabetic neuropathy by VEGF gene transfer

The pathogenetic basis for diabetic neuropathy has been enigmatic. Using two different animal models of diabetes, we have investigated the hypothesis that experimental diabetic neuropathy results from destruction of the vasa nervorum and can be reversed by administration of an angiogenic growth factor. Nerve blood flow, as measured by laser Doppler imaging or direct detection of a locally administered fluorescent lectin analogue, was markedly attenuated in rats with streptozotocin-induced diabetes, consistent with a profound reduction in the number of vessels observed. A severe peripheral neuropathy developed in parallel, characterized by significant slowing of motor and sensory nerve conduction velocities, compared with nondiabetic control animals. In contrast, 4 weeks after intramuscular gene transfer of plasmid DNA encoding VEGF-1 or VEGF-2, vascularity and blood flow in the nerves of treated animals were similar to those of nondiabetic control rats; constitutive overexpression of both transgenes resulted in restoration of large and small fiber peripheral nerve function. Similar experiments performed in a rabbit model of alloxan-induced diabetes produced comparable results. These findings support the notion that diabetic neuropathy results from microvascular ischemia involving the vasa nervorum and suggest the feasibility of a novel treatment strategy for patients in whom peripheral neuropathy constitutes a secondary complication of diabetes.     

Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies.

Neurotrophic factors (NFs) are promising agents for the treatment of peripheral neuropathies such as diabetic neuropathy. However, the value of treatment with recombinant NF is limited by the short half-lives of these molecules, which reduces efficiency, and by their potential toxicity. We explored the use of intramuscular injection of a recombinant adenovirus encoding NT-3 (AdNT-3) to deliver sustained low doses of NT-3. We assessed its effect in two rat models: streptozotocin (STZ)-induced diabetes, a model of early diabetic neuropathy characterized by demyelination, and acrylamide experimental neuropathy, a model of diffuse axonal neuropathy which, like late-onset human diabetic neuropathy, results in a diffuse sensorimotor neuropathy with dysautonomy. Treatment of STZ-diabetic rats with AdNT-3 partially prevented the slowing of motor and sensory nerve conduction velocities (p < 0.01 and p < 0.0001, respectively). Treatment with AdNT-3 of acrylamide-intoxicated rats prevented the slowing of motor and nerve conduction velocities (p < 0.001 and p < 0.0001, respectively) and the decrease in amplitude of compound muscle potentials (p < 0.0001), an index of denervation. Acrylamide-intoxicated rats treated with NT-3 had higher than control levels of muscle choline acetyltransferase activity (p < 0.05), suggesting greater muscle innervation. In addition, treatment of acrylamide-intoxicated rats with AdNT-3 significantly improved behavioral test results. Treatment with AdNT-3 was well tolerated with minimal muscle inflammation and no detectable general side effects. Therefore, our results suggest that NT-3 delivery by adenovirus-based gene therapy is a promising strategy for the prevention of both early diabetic neuropathy and axonal neuropathies, especially late axonal diabetic neuropathy.     

托吡酯治疗糖尿病周围神经病疗效观察

目的观察托吡酯治疗糖尿病周围神经病的临床疗效。方法83例糖尿病周围神经病患者随机分成对照组40例和治疗组43例,均给予常规降糖及B族维生素支持治疗,治疗组同时给予托吡酯治疗1个月。结果治疗组及对照组的临床总有效率分别为90.7%和67.5%,差异有显著性意义（P〈0.05）。治疗后,两组患者的感觉及运动神经传导速度明显提高,但治疗组的传导速度显著高于对照组（P〈0.001）。结论在控制血糖基础上,加用托吡酯治疗糖尿病周围神经病临床疗效确切,副作用少。     

风险分级管理模式对糖尿病足溃疡预防效果的Meta分析

目的：评价风险分级管理模式对糖尿病足溃疡的预防效果。方法：运用Meta分析法,检索中英文数据库搜集风险分级管理模式对糖尿病足溃疡预防效果的临床随机对照试验,参照Cochrane系统评价手册5.1.0进行文献质量评价,采用RevMan 5.3软件进行Meta分析。 结果：最终纳入8篇随机对照试验（RCT）研究,1295例研究对象。相较于对照组,风险分级管理模式降低了3% 的糖尿病足溃疡发生风险,差异有统计学意义[RD=-0.03, 95%CI(-0.05,0.00), P=0.04]。风险分级管理组的动脉踝肱指数（ABI）高于对照组,差异有统计学意义（P＜0.001）。同时,风险分级管理组的运动神经传导速度[MD=3.53, 95%CI(2.02,5.05), P<0.01]和感觉神经传导速度[MD=4.53, 95%CI（2.93,6.13）,P<0.01]优于对照组,且有统计学意义。结论：风险分级管理模式在糖尿病足溃疡预防的应用效果显示出优越性。相较于常规健康管理,该管理模式可以降低DF的发病率,明显改善患者动脉血管及周围神经状况。     

C-peptide: new findings and therapeutic implications in diabetes

In contrast to earlier views, new data indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C-peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G-protein coupled receptor. Ca(2+)- and MAP-kinase dependent signalling pathways are activated, resulting in stimulation of Na(+), K(+)-ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C-peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C-peptide administration in streptozotocin-diabetic animals results in normalization of diabetes-induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C-peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C-peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C-peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C-peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C-peptide is the ugly duckling that--nearly 40 years after its discovery--may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long-term complications.     

黄芪桂枝五物汤治疗糖尿病周围神经病变气虚血瘀证Meta分析

目的:系统评价黄芪桂枝五物汤治疗糖尿病周围神经病变(气虚血瘀证)安全性和有效性。方法:检索中国知网(CNKI)、中国生物医学文献数据库(CBM)、维普全文数据库(VIP)、万方医学网、PubMed,检索至2020年04月正式发表的黄芪桂枝五物汤治疗糖尿病周围神经病变的文献,按照纳入标准和排除标准,纳入文献,提取资料,采用RevMan 5.3进行Meta分析。结果:共纳入14篇文献,1062例患者,实验组532例,对照组530例。在临床疗效、正中神经(运动纤维)传导速度、正中神经(感觉纤维)传导速度、腓总神经(运动纤维)传导速度上,两组差异具有统计学意义,空腹血糖、餐后2h血糖无明显统计学差异。结论:在现有文献基础上,黄芪桂枝五物汤治疗糖尿病周围神经病变(气虚血瘀证)可提高临床疗效,提高正中神经(运动纤维)、正中神经(感觉纤维)、腓总神经(运动纤维)传导速度。     

2型糖尿病患者周围神经传导速度有关因素分析

目的 评价影响2型糖尿病患者周围神经传导速度的因素。方法 对157例2型糖尿病患者进行周围神经传导速度测定,并就其与病程、尿白蛋白排泄和糖化血红蛋白的关系进行分析。结果 ①在病程<5年、5～10年、10-15年和超过15年的患者中,周围感觉神经电生理异常的发生率随病程的延长而显著增高,P<0.05;而运动神经早期多不明显,仅在病程超过10年的患者中,其神经传导速度才明显减慢;②在正常、微量和大量白蛋白尿的患者中,感觉神经电生理异常的发生率随尿白蛋白排泄的增加而增高,大量白蛋白尿患者周围运动神经波幅明显降低,传导速度显著减慢;③与正常对照组比较,糖尿病患者,糖化血红蛋白水平显著升高,P<0.01。结论 糖尿病患者周围神经病变与病程、尿白蛋白排泄和血糖控制有关。     

果糖二磷酸钠联合α-硫辛酸治疗糖尿病周围神经病变临床效果观察

目的 观察果糖二磷酸钠与α-硫辛酸联合治疗糖尿病周围神经病变的临床疗效.方法 66例糖尿病患者随机分为治疗组34例(其中3例因不能耐受退出该研究),对照组32例.在控制血糖的基础上,治疗组给予果糖二磷酸钠10 g、α-硫辛酸0.45 g,静脉滴注.对照组给予α-硫辛酸0.45 g,静脉滴注.2组均为1次/d,疗程2周.观察治疗后症状改善情况,并测定治疗前后正中神经和腓总神经的运动传导速度和感觉传导速度.结果 治疗2周后,治疗组总有效率93.55%(28/31),对照组总有效率68.75%(22/32),治疗组临床疗效较对照组明显改善(P<0.05).运动神经传导速度治疗组[正中神经为(47.7±3.8)m/s与(42.5±2.5)m/s,腓总神经为(41.6±3.3)m/s与(36.0±2.8)m/s]与对照组[正中神经为(43.4±2.0)m/s与(41.9±16.0)m/s、腓总神经为(39.6±3.3)m/s与(36.2±1.9)m/s]和感觉神经传导速度[正中神经为(40.3±1.8)m/s与(35.2±2.3)m/s、腓总神经为(34.1±2.3)m/s与(28.8±2.5)m/s]、对照组[正中神经为(37.7±1.7)m/s与(34.8±3.1)m/s、腓总神经为(30.8±2.6)m/s与(27.8±2.4)m/s]均较治疗前提高(P均<0.05),但治疗组提高更明显(P<0.01).结论 果糖二磷酸钠与α-硫辛酸联合治疗糖尿病周围神经病变,疗效较好.     

血糖变异性参数与痛性糖尿病周围神经病变的相关性

目的探讨血糖变异性参数与痛性糖尿病周围神经病变(PDPN)的关系。方法选取2型糖尿病(T2DM)合并周围神经病变(DPN)患者135例[PDPN患者58例(PDPN组)和非痛性糖尿病周围神经病变(NPDPN)患者77例(NPDPN组)]、单纯T2DM患者63例(单纯T2DM组)和体检健康者42名(正常对照组)。收集所有对象的一般资料,并检测其糖化血红蛋白(HbA_1c)、空腹血糖(FBG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、血脂[三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、脑源性神经营养因子(BDNF)、高迁移率族蛋白B1(HMGB1)、血糖变异性参数[日内最大血糖波动幅度(LAGE)、全天血糖平均值(MBG)、全天血糖标准差(SDBG)、空腹血糖变异系数(FBG-CV)]以及神经传导速度[正中神经运动神经传导速度(MMCV)、腓总神经运动神经传导速度(PMCV)、正中神经感觉神经传导速度(MSCV)及腓总神经感觉神经传导速度(PSCV)]。采用受试者工作特征(ROC)曲线分析血糖变异性参数对PDPN的诊断价值。采用非条件Logistic回归分析评估PDPN的影响因素。采用Kaplan-Meier曲线评估PDPN患者心血管疾病及致残的发生风险。采用Spearman相关分析评估各项指标之间的相关性。结果PDPN组、NPDPN组及单纯T2DM组体质量指数(BMI)、糖尿病病程、FBG、2 h PG、TG、HDL-C、HbA_1c、BDNF、HMGB1、MMCV、PMCV、MSCV、PSCV与正常对照组比较,差异均有统计学意义(P<0.05、P<0.01)。PDPN组FBG、TG、HbA_1c、BDNF、HMGB1、PSCV与NPDPN组、单纯T2DM组比较,差异有统计学意义(P<0.05、P<0.01)。ROC曲线分析结果显示,LAGE、MBG、SDBG、FBG-CV诊断PDPN的曲线下面积(AUC)分别为0.748、0.727、0.785、0.837,FBG-CV诊断PDPN的效能优于LAGE、MBG、SDBG。Spearman相关分析结果显示,LAGE、MBG、SDBG、FBG-CV与BDNF、PMCV显著相关(P<0.05)。非条件Logistic回归分析结果显示,LAGE、MBG、SDBG、FBG-CV是PDPN发生的危险因素。PDPN组心血管事件累积发生率显著高于NPDPN组(P=0.017)。以FBG-CV诊断PDPN的最佳临界值30.00%进行分组,结果显示,FBG-CV≥30.00%组心血管事件累积发生率显著高于FBG-CV<30.00%组(P=0.013)。结论血糖变异性参数可能与PDPN有关,且是PDPN患者远期发生心血管事件的独立危险因素。     

Correlations among autonomic, sensory, and motor neural function tests in untreated non-insulin-dependent diabetic individuals

A well-defined group of untreated non-insulin-dependent (NIDD) subjects were evaluated to determine whether involvement of neural function measurements is generalized and symmetrical and to compare the autonomic, sensory, and motor neural measurements. After age adjustment, the sensory and motor neural function measurements were significantly slower in the diabetic group than in normal subjects (P less than 0.01). Similarly, the autonomic nervous system function measurements were also abnormal in the NIDD group (P less than 0.01). Further analysis revealed that each of the specific measurements--median motor nerve conduction velocity (NCV,P less than 0.005), peroneal motor NCV (P less than 0.005), median sensory NCV (P less than 0.005), dark-adapted pupil size after muscarinic blockade (P less than 0.02), pupillary latency time (P less than 0.02), and RR-variation after beta adrenergic blockade (P less than 0.001)--was significantly less by analysis of covariance after age adjustment in the NIDD group than in normal subjects. Thus, there was evidence of motor and sensory neural impairment in the upper and lower extremities as well as evidence of impairment of the reflex arcs involving the parasympathetic nerves to the heart and eye and the sympathetic nerves to the iris. Further analysis revealed that right and left NCV were correlated (P less than 0.01), as were the median motor and median sensory NCV (P less than 0.01), the median motor and peroneal motor NCV (P less than 0.001), and the peroneal motor and median sensory NCV (P less than 0.001). Thus, there was evidence of symmetrical upper and lower limb, as well as motor and sensory proportional involvement of large nerve fiber NCV in this group of NIDD subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

糖尿病患者下肢周围神经传导速度分析

目的　探讨下肢周围神经传导速度检测对糖尿病周围神经病变 (DPN )的早期诊断价值及评价DPN程度的意义。方法　对 5 3例糖尿病患者下肢F波、运动神经、感觉神经的传导速度检测 ,分析糖尿病患者中有、无神经系统自觉症状组 ,1型、2型糖尿病组的周围神经传导速度变化。结果　各观察组神经传导速度较正常值减慢 (P <0 .0 1) ;有症状组与无症状组比较 ,F波、运动神经传导速度减慢加重 (P <0 .0 1) ,感觉神经传导比较尚无统计学意义 (P >0 .0 5 ) ;1型糖尿病神经传导速度减慢较 2型为重 (P <0 .0 1)。结论　下肢周围神经传导速度减慢是DPN早期诊断及评价DPN程度的敏感指标。     

Effects of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy

BACKGROUND: Nonenzymatic glycation of neural proteins and their end-products (advanced glycation end-products, AGE) have been implicated in the pathogenesis of diabetic neuropathy. We need a development of effective ant-glycation agents for future clinical use. MATERIALS AND METHODS: We examined the effects of OPB-9195 (OPB), a new inhibitor of glycation, on the peripheral nerve structure and function in diabetic rats. Eight-week-old Wistar rats were made diabetic by streptozotocin (40 mg kg(-1), i.v.) and OPB (60 mg kg(-1) day(-1)) was given by gavage for 24 weeks. Age- and sex-matched normal Wistar rats were used for comparison. RESULTS: During the experimental period, OPB treatment did not affect the reduced body weight, elevated levels of blood glucose and glycated haemoglobin in diabetic rats. At the end of the experiment, delayed tibial motor nerve conduction velocity was significantly improved (by 60%) in treated diabetic rats, with reduction of serum AGE levels. Expression of immunoreactive AGE in the sciatic nerve was reduced in treated diabetic rats compared with those in untreated rats. Sciatic nerve (Na+, K+)-ATPase activity was also restored in treated diabetic rats. On the cross-sectioned sciatic nerves, positive cells with oxidative stress-related DNA damage, as expressed by 8-hydroxy-2'-deoxyguanosine, were less in the peripheral nerve of treated diabetic rats compared with those of untreated rats. CONCLUSION: The current study suggested that OPB is beneficial for the reduction of serum AGE and the prevention of diabetic neuropathy.     

实验性糖尿病大鼠胰岛素样生长因子-1基因表达异常与神经电生理及外周神经病变

目的探讨糖尿病时肝组织胰岛素样生长因子-1(IGF-1)基因表达的异常及其与糖尿病外周神经病变的关系. 方法分离解剖出右侧坐骨神经,测定诱发电位出现的波幅 (amplitude of evoked potentials ,AEP)、感觉及运动神经传导速度 (sensory /motor nerve conduction velocity, SNCV/MNCV),用四氧嘧啶诱发糖尿病 SD大鼠模型. 48只糖尿病大鼠按经(胰岛素)控制后血糖水平分成 3组 ID-1, 2, 3组 ,16只正常大鼠用作对照组.反转录一多聚酶链扩增反应半定量分析坐骨神经 IGF-1 mRNA含量;酶联免疫吸附法分析组织 IGF-1肽含量;诱发肌电图测定坐骨神经电生理指标;观察坐骨神经形态学改变. 结果病程早期( 2周 ,2个月),正常对照组、 ID-2组大鼠肝组织 IGF-1mRNA含量( 1.15± 0.090, 0.79± 0.048, P < 0.001;1.17± 0.069,0.53± 0.023, P< 0.001)、肽含量均下降 [(196.66± 14.9), (128.2± 11.25) μ g/g, P< 0.001;(196.66± 14.9), (74.43± 5.33) μ g/g, P < 0.001]出现在相应糖尿病组大鼠坐骨神经电生理指标异常之前,程度均随糖尿病控制状态而异,且随病程进一步逐渐下降 [IGF-1 mRNA(0.71± 0.024)～ (0.47± 0.021);IGF-1 肽 (114.35± 8.09)～ ( 64.58± 3.89) μ g/g,P < 0.001].血清 IGF-1呈一致性下降 (r=0.99,P< 0.001).其变化与坐骨神经功能改变(感觉神经r=0.54,P< 0.05, 运动神经 r=0.49, P< 0.05)、组织形态异常关系密切 (神经纤维密度 r=0.68,P< 0.05),血糖正常糖尿病组大鼠与正常对照组间上述指标差异无显著性意义. 结论糖尿病早期即出现肝组织 IGF-1基因表达下降,程度依糖尿病严重状态而异并随疾病进程加重,血清 IGF-1水平相应地出现变化,提示肝组织为血循环 IGF-1的主要来源.这种表达异常可能导致外周神经病变发生和发展.