依达拉奉对糖尿病周围神经病变氧化应激和神经传导速度的影响

目的 观察依达拉奉对糖尿病周围神经病变(DPN)患者氧化应激状态和神经传导速度的影响,评价疗效.方法 40例DPN患者予依达拉奉60mg/d,静脉滴注2周,检测治疗前后氧化和抗氧化系统指标和神经传导速度,并进行总体症状评分(TSS).结果 治疗后DPN患者血清一氧化氮(NO)、丙二醛(MDA)含量明显降低,超氧化物歧化酶(SOD)活力明显提高,运动神经传导速度(MCV)、感觉神经传导速度(SCV)显著增快,TSS评分明显下降,差异均有统计学意义(P＜0.01).结论 依达拉奉可抑制DPN患者氧化应激,提高神经传导速度,改善临床症状.     

硫辛酸胶囊对糖尿病周围神经病变模型大鼠的药效学研究

目的:探讨硫辛酸胶囊对糖尿病周围神经病变(DPN)大鼠的作用及初步机制作用。方法:选取健康无特定病原体级的SD大鼠60只,雄性,体质量(220±20)g。采用大鼠腹腔注射链脲佐菌素(STZ)的方法诱导糖尿病大鼠成模,取成功造成DPN模型的30只大鼠按体质量随机分组法随机分为模型组、硫辛酸组及阳性药组,同时取正常大鼠10...     

褪黑素对糖尿病周围神经病变大鼠氧化应激及周围神经功能和形态的作用

背景:课题组前期针对糖尿病肾病的实验显示,褪黑素可以显著提高糖尿病大鼠血浆和肾脏内抗氧化酶的活性,改善肾脏的形态学变化。目的:在前期实验的基础上,进一步观察褪黑素对糖尿病周围神经病变大鼠氧化应激和周围神经功能和形态的作用。设计、时间及地点:随机对照动物试验,于2005-04/11在解放军第二军医大学动物实验中心完成。材料:2月龄健康雄性SD大鼠,单次腹腔注射链脲佐菌素60mg/kg诱导建立糖尿病大鼠模型。方法:将糖尿病模型大鼠维持饲养8周建立糖尿病周围神经病变大鼠模型,然后按体质量随机分为3组:模型组,褪黑素0.5,10mg/(kg·d)组,以未造模、鼠龄及体质量相匹配的8只大鼠为正常对照组。褪黑素0.5,10mg/(kg·d)组大鼠每日16:00灌胃给予相应剂量的褪黑素,其他2组大鼠予等量体积分数为0.02的乙醇溶液灌胃,持续8周。主要观察指标:检测各组大鼠坐骨神经内超氧化物歧化酶、谷胱甘肽过氧物酶活性和脂质过氧化产物丙二醛含量的变化,大鼠摆尾阈值、坐骨神经神经传导速度和超微结构的变化。结果:各组糖尿病大鼠坐骨神经传导速度显著低于正常对照组(P<0.01),褪黑素0.5,10mg/(kg·d)治疗后神经传导速度高于模型组(P<0.05,0.01)。褪黑素0.5,10mg/(kg·d)组丙二醛含量低于模型组(P<0.01),血清超氧化物歧化酶、谷胱甘肽过氧物酶活性高于模型组(P<0.01)。模型组大鼠坐骨神经多数有髓纤维髓鞘板结构破坏严重,出现裂隙、空泡等现象,轴突严重被挤压,轴突变性、萎缩。褪黑素治疗后坐骨神经纤维的髓鞘仍不正常,但较模型组明显减轻,褪黑素10mg/(kg·d)组改变要好于褪黑素0.5mg/(kg·d)组。结论:褪黑素能有效抑制糖尿病周围神经病变大鼠的氧化应激反应,改善神经功能和结构变化。糖尿病时自由基损伤和抗氧化能力的降低可能在糖尿病周围神经病变的发生发展中发挥重要作用。     

2型糖尿病周围神经病变与血清超氧化物歧化酶活性的关系

目的探讨血清超氧化物歧化酶(SOD)活性在2型糖尿病(T2DM)周围神经病变检测中的临床应用价值。方法选取125例T2DM周围神经病变患者及125例健康者,用邻苯三酚比色法测定其血清SOD活性。比较T2DM周围神经病变患者与健康者血清SOD活性,分析T2DM周围神经病变患者血清SOD活性与患者性别、年龄及血糖水平的关系。结果 T2DM周围神经病变组血清SOD活性与对照组比较差异有统计学意义(t=7.798,P=0.000)。T2DM周围神经病变患者血清SOD活性与患者性别、年龄无关;血糖水平6.1~<7.0mmol/L、≥7.0mmol/L组患者间SOD活性的比较,差异有统计学意义(P=0.034)。结论 T2DM周围神经病变患者血清SOD活性水平增高且与血糖水平有关,可能随血糖水平升高而增高。     

运动对糖尿病大鼠认知功能的影响

目的 探讨运动对糖尿病大鼠认知功能的影响。方法将雌性SD大鼠30只随机分为3组：正常对照组（n=10）、糖尿病组（n=10）和糖尿病运动组（n=10）。采用链脲佐菌素（STZ）腹腔内注射建立糖尿病模型。糖尿病运动组大鼠每日游泳训练1次,共计运动3个月。分别在建模前和建模后3个月检测大鼠的血糖和体质量,Morris水迷宫测试大鼠学习记忆能力,免疫组织化学方法检测脑组织海马区纤维连接蛋白（Fn）分布情况。结果成模后,糖尿病组和糖尿病运动组大鼠血糖均高于正常对照组（P〈0．01）。大鼠学习记忆能力,糖尿病组与正常对照组相比显著下降（P〈0．01）;糖尿病运动组明显好于糖尿病组（P〈0．01）。海马区脑组织Fn阳性区域,糖尿病组比正常对照组显著增加（P〈0．01）;糖尿病运动组增加不明显（P〉0．05）。结论运动可以改善糖尿病大鼠的学习记忆能力,并对糖尿病大鼠血-脑脊液屏障起保护作用。     

依达拉奉对糖尿病周围神经病变大鼠坐骨神经的保护作用

目的:研究依达拉奉对糖尿病周围神经病变(DPN)大鼠坐骨神经的保护作用。方法:SD大鼠80只,采用链脲佐菌素(STZ)一次性腹腔注射诱导建立DPN模型,随机分为对照组和治疗组,治疗组每天给予3 mg/kg依达拉奉腹腔注射4周,观察摆尾温度阈值(TTT)、坐骨神经运动神经传导速度(MCV)、感觉神经传导速度(SCV)、神经形态和坐骨神经中一氧化氮(NO)含量、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性。结果:对照组大鼠TTT升高,MCV和SCV减慢(P<0.01),形态学明显异常,NO、MDA含量明显增多,SOD活性显著降低(P<0.01)。治疗组与对照组比较TTT明显降低,MCV和SCV明显加快,形态学明显改善,NO、MDA含量明显减少,SOD活性显著增高(P<0.01)。结论:依达拉奉可降低DPN大鼠坐骨神经损伤。     

综合性护理对糖尿病周围神经病变病人疗效及神经传导速度的影响

[目的]探讨综合护理对糖尿病病人周围神经病变的影响。[方法]将80例糖尿病周围神经病变的病人采用计算机编号的方法随机分为观察组和对照组各40例,对照组采用常规护理,观察组在常规护理基础上采用综合性护理。比较两组的血糖变化、临床疗效及神经传导速度的变化。[结果]观察组病人护理后的空腹血糖和餐后2h血糖的下降水平大于对照组(P0.05);观察组病人总有效率为95.0%,高于对照组的77.5%(P0.05);观察组病人护理后尺神经、正中神经、腓总神经传导速度增快,且大于对照组(P0.05)。[结论]综合性护理能够改善糖尿病周围神经病变病人的神经传导速度,减轻临床症状,提高治疗效果。     

中药泡脚联合雷火灸对糖尿病周围神经病变的影响研究

目的:探讨中药泡脚联合雷火灸对糖尿病周围神经病变(DPN)病人疼痛评分、密歇根神经病变(MNSI)评分及神经传导速度的影响。方法:选取本院收治的82例DPN病人,按随机数字表法分为对照组和观察组各41例。对照组予以常规对症治疗,观察组加用中药泡脚联合雷火灸治疗,持续治疗4周。比较两组临床疗效、疼痛评分、MNSI评分、神经传导速度变化。结果:观察组总有效率为95.12%,高于对照组的80.49%,差异有统计学意义(P<0.05);观察组治疗后疼痛评分、MNSI评分分别为(1.45±0.24)分、(5.89±1.12)分,均低于对照组,差异有统计学意义(P<0.05);观察组治疗后胫神经SNCV、腓总神经MNCV为(46.52±4.17)m/s、(48.96±4.28)m/s,高于对照组,差异有统计学意义(P<0.05)。结论:中药泡脚联合雷火灸在DPN病人中应用效果确切,可减轻神经组织损伤,降低疼痛评分,加快神经传导速度。     

复方丹参注射液辅助治疗对糖尿病周围神经病变传导速度的作用

采用复方丹参注射液辅助治疗糖尿病周围神经病变40例，结果治疗后正中神经，腓神经运动传导速度和感觉传导速度与治疗前相比均明显增快。与常规治疗的40例比较差异有显性意义。     

依帕司他治疗糖尿病周围神经病变大鼠的疗效评价

目的探讨依帕司他对糖尿病周围神经病变(DPN)大鼠坐骨神经功能、醛糖还原酶(AR)活性、Na+-K+-ATP酶活性及cAMP和cGMP含量的影响。方法给予动物灌胃给药,连续8周。观察DPN大鼠坐骨神经传导速度、坐骨神经AR活性、Na+-K+-ATP酶活性及cAMP和cGMP含量的变化。结果依帕司他可以提高DPN大鼠坐骨神经传导速度,降低AR活性,提高Na+-K+-ATP酶活性,增加cAMP和cGMP含量。结论依帕司他对DPN大鼠周围神经功能有显著的保护作用。     

甲钴胺联合前列地尔治疗糖尿病周围神经病变的疗效及安全性

目的探讨甲钴胺联合前列地尔治疗糖尿病周围神经病变(DPN)的疗效及安全性。方法选取DPN患者138例,随机分为A、B、C 3组,每组46例。在常规治疗基础上,A组给予前列地尔注射液,B组给予甲钴胺注射液,C组给予前列地尔注射液联合甲钴胺注射液,疗程均为14 d。观察3组临床疗效和不良反应发生率,比较3组治疗前后神经传导速度和神经病变症状总评分(TSS)。结果 A、B、C 3组总有效率(ORR)分别为76.09%、73.91%、91.30%,C组ORR显著高于其他组(P0.05)。治疗后,3组TSS均显著低于治疗前(P0.01),运动神经传导速度(MCV)和感觉神经传导速度(SCV)均显著高于治疗前(P0.05或P0.01),且C组升高程度高于其他组(P0.01)。3组不良反应发生率比较无显著差异(P0.05)。结论在治疗DPN方面,甲钴胺联合前列地尔的临床疗效优于两药单用,且不良反应少,安全性高。     

血糖波动对老年糖尿病患者氧化应激指标及胰岛β细胞功能的影响

目的检测老年糖尿病患者氧化应激和动态血糖监测（CGMS）相关指标,探讨血糖波动与老年糖尿病患者胰岛β细胞分泌功能之间关系。 方法选取2015-01至2016-01上海市浦东新区周浦医院内分泌科住院的老年糖尿病患者60例,应用CGMS进行连续72 h血糖监测,同时检测血清胰岛素、糖化血红蛋白（HbA1c）、血浆丙二醛含量（MDA）、超氧化物歧化酶水平（SOD）、8-异前列腺素F2α（8-iso-PGF2α）等。根据CGMS数据计算平均血糖波动幅度（MAGE）,胰岛β细胞功能采用稳态模式评估法的胰岛素分泌指数（HOMA-β）表示。 结果MAGE与HOMA-β、SOD呈负相关（P<0.05）、与8-iso-PG、MAD呈正相关（P<0.05）,MAGE与HbA1c无明显相关（P>0.05）,多元逐步回归分析显示HOMA-β与MAGE、体质量指数（BMI）相关。 结论老年糖尿病患者血糖波动与胰岛素分泌缺陷密切相关,血糖波动可能通过氧化应激这一关键环节加重对胰岛β细胞功能的损害。     

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.     

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.     

银杏叶提取物对精神分裂症患者认知功能及氧化应激的影响

目的分析精神分裂症患者银杏叶提取物治疗前后外周血中氧化应激指标和认知功能的差异,并进一步分析二者间的联系。方法选取2018年1月至2019年1月精神分裂症患者140例,分为观察组和对照组各70例,应用重复性成套神经心理状态测验(RBANS)评定精神分裂症患者的认知功能水平,同时分别于治疗前后检测外周血中氧化应激指标:GSH-Px、MDA的含量和SOD活性,收集并整理数据,运用SPSS 20.0对数据进行统计分析。结果①观察组GSH-Px差值、MDA差值、SOD差值、RBANS总分差值及各因子分差值明显高于对照组(P<0.001);②银杏叶提取物治疗后观察组GSH-Px、SOD含量高于治疗前,MDA含量低于治疗前,RBANS总分以及各因子分高于治疗前(P<0.001);③治疗过程中精神分裂症患者GSH-Px差值和SOD差值与RBANS总分差值及即刻记忆、言语功能、注意功能以及延时记忆因子差值呈正相关(P<0.05),MDA差值与RBANS总分差值及各因子差值呈正相关(P<0.05)。结论银杏叶提取物可以减轻精神分裂症患者的氧化应激和认知功能损害。     

α-硫辛酸治疗2型糖尿病周围神经病变

目的评价α-硫辛酸对2型糖尿病周围神经病变(DPN)的疗效。方法45例DPN的患者随机分为两组,治疗组23例,给予α-硫辛酸600 mg加液体静脉点滴,1次/d,共2周;对照组22例,给予甲钴胺1 000μg加液体静脉点滴,1次/d,共2周。观察临床症状和体征变化及神经传导速度(NCV),检测血C反应蛋白(CRP)、谷胱甘肽、尿微量白蛋白。结果治疗组有效率达91.3%,明显高于对照组的63.6%(P<0.05);治疗后两组神经传导速度均较治疗前明显改善(P<0.01)。结论α-硫辛酸治疗DPN,疗效显著。     

Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats.

OBJECTIVES: The objectives of this study were to examine the role of reactive oxygen species and oxidative stress in peripheral neuropathy and behavioural pain responses in experimentally induced chronic constriction injury (CCI) of sciatic nerve of rat. Effect of N-acetyl-L-cysteine (NAC) administered intraperitoneally, was also investigated on CCI-induced neuropathic pain in rats. METHODS: Neuropathy was induced by CCI of the right sciatic nerve in ketamine anaesthetized rats. Effect of intraperitoneally administered NAC in rats was also investigated using nociceptive behavioural tests. Malondialdehyde, an index of oxidative stress and antioxidant enzymes was also estimated in ligated sciatic nerve. RESULTS: Behavioural tests, mechanical, thermal and cold stimuli confirmed the development of neuropathic pain after the CCI. The malondialdehyde levels of ligated sciatic nerves were significantly increased compared to non-ligated sciatic nerves (sham operated). The antioxidant enzyme reduced, glutathione was inhibited, while superoxide dismutase increased. However, catalase remained unaffected in the injured sciatic nerves. Intraperitoneal administration of NAC resulted in significant reduction of hyperalgesia in CCI-induced neuropathic rats. CONCLUSIONS: This study identifies antioxidants superoxide dismutase and reduced glutathione, and oxidative stress as important determinants of neuropathological and behavioural consequences of CCI-induced neuropathy, and NAC may be a potential candidate for alleviation of neuropathic pain.     

硫酸锌联合甲钴胺治疗糖尿病周围神经病变的临床观察

目的探讨硫酸锌和甲钴胺单独应用及二者联合应用治疗糖尿病周围神经病变(DPN)的临床效果。方法选取DPN患者105例,随机分为硫酸锌组、甲钴胺组合联合组,每组35例,3组患者均给予控制血糖、血压等糖尿病综合治疗。分别应用硫酸锌片、甲钴胺片及硫酸锌片联合甲钴胺片治疗DPN,观察患者临床症状及体征,测定患者治疗1月后正中神经和腓总神经的运动传导速度(MNCV)和感觉传导速度(SNCV)。结果治疗后,联合组正中神经和腓总神经的MNCV均显著高于硫酸锌组和甲钴胺组(P0.05);联合组正中神经SNCV显著高于硫酸锌组和甲钴胺组(p0.05),联合组腓总神经的SNCV与硫酸锌组和甲钴胺组比较差异无统计学意义(P=0.259)。联合组临床总有效率显著高于其他2组(P=0.002)。结论硫酸锌联合甲钴胺片治疗DPN对正中神经和腓总神经MNCV及正中神经的SNCV改善程度要优于单独应用硫酸锌和甲钴胺片。     

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.