BDNF和NT-3在糖尿病周围神经病大鼠肌肉中的表达

目的观察链脲佐菌素(Streptozotocin STZ)诱导的糖尿病周围神经病大鼠腓肠肌脑源性神经生长因子(BDNF)、神经营养素-3(NT-3)的mRNA表达。方法用STZ复制Wistar大鼠糖尿病周围神经病模型。成模8周、12周麻醉后处死大鼠,提取腓肠肌组织RNA,应用RT-PCR半定量方法检测其BDNF及NT-3mRNA含量。结果糖尿病周围神经病组大鼠腓肠肌BDNF的mRNA含量明显高于正常对照组(P<0.01),12周糖尿病周围神经病大鼠组明显高于8周糖尿病周围神经病大鼠组(P<0.01);腓肠肌NT-3的mRNA含量各组间无显著性差异(P>0.05)。结论糖尿病周围神经病大鼠腓肠肌组织BDNF的mRNA含量随着病程逐渐增加,而NT-3的mRNA含量无明显变化,二者在糖尿病周围神经病中发挥不同作用。     

人神经生长因子对DPN大鼠坐骨神经CGT的作用

目的　观察人神经生长因子 ( h NGF)对早期糖尿病多发性神经病 ( DPN)大鼠坐骨神经中半乳糖神经酰胺转移酶 m RNA( CGTm RNA)表达的影响。方法　用链脲佐菌素 ( STZ)一次性腹腔注射诱导糖尿病大鼠模型 ,在 DPN 4周 (造模后 4周 )腹腔注射 h NGF( 90 U .kg- 1 .d- 1 ) ,共 4周。用 RT- PCR和免疫组化方法观察坐骨神经CGTm RNA,NGFm RNA和蛋白表达。结果　 DPN 8周大鼠坐骨神经 CGTm RNA升高 ,NGFm RNA和蛋白表达减少。用 h NGF治疗的 DPN大鼠 CGTm RNA明显降低 ,NGFm RNA和蛋白表达增加。结论　 h NGF治疗能纠正早期DPN大鼠坐骨神经 CGTm RNA异常     

氢气抑制核因子-κB通路对糖尿病周围神经病变的保护作用

目的观察氢气对链脲霉素致糖尿病周围神经病变模型大鼠坐骨神经功能和疼痛行为学的影响,并探讨其可能的作用机制。方法腹腔注射链脲霉素(65 mg/kg)建立糖尿病大鼠模型,6周后腹腔注射富氢生理盐水(5 ml/kg),连续治疗2周后观察不同处理组大鼠坐骨神经功能和疼痛行为学变化,并检测坐骨神经炎性因子[肿瘤坏死因子α(TNFα)和白细胞介素6(IL 6)]及核因子κB(NFκB)p65亚基表达变化。结果 (1)与正常对照组相比,模型制备成功第8周时模型组大鼠体质量降低、血糖水平升高(均P=0.000);与模型组相比,氢气治疗组大鼠体质量和血糖水平无明显改善(均P>0.05)。(2)与正常对照组相比,模型制备成功第8周时模型组大鼠坐骨神经传导速度减慢、热痛阈和机械性痛阈降低(均P=0.000);而与模型组相比,氢气治疗后大鼠坐骨神经传导速度增加、热痛阈和机械性痛阈提高(均P=0.000)。(3)经氢气治疗后,大鼠坐骨神经TNFα和IL 6表达水平降低(均P=0.000),NFκB p65亚基阳性细胞数目减少(P=0.000)。结论糖尿病周围神经病变与炎症反应有关,而氢气可以通过抑制NFκB及其下游炎性因子的表达而发挥对糖尿病周围神经损害的保护作用。     

人神经生长因子对糖尿病多发性神经病大鼠坐骨神经caloainⅡ的作用

目的:观察人神经生长因子(hNGF)对早期糖尿病多发性神经病(DPN)大鼠坐骨神经中calpainⅡ表达的影响。方法:用链佐星(STZ)一次性腹腔注射诱导糖尿病大鼠模型,在DPN4周(造模后4周)腹腔注射hNGF90U/(kg·d),共4周。用原位杂交和免疫组化方法观察坐骨神经calpainⅡmRNA和蛋白表达。结果:DPN8周大鼠坐骨神经calpainⅡmRNA和蛋白表达明显减少。用hNGF治疗的DPN大鼠calpainⅡmRNA和蛋白表达增加。结论:hNGF治疗能纠正早期DPN大鼠坐骨神经calpainⅡmRNA和蛋白表达异常。     

糖尿病对大鼠脑缺血的影响

目的建立稳定的慢性实验性糖尿病大鼠脑缺血再灌注损伤模型,明确糖尿病与正常大鼠脑缺血损伤的异同。方法以链脲佐菌素诱导产生实验性糖尿病大鼠,饲养6~7周,经测定血糖≥16.7mmol/L确定糖尿病模型的建立。以线栓法制作大鼠脑缺血再灌注模型,进行神经功能评分,采用TTC染色进行梗死体积测定,HE染色观察病理学变化。结果糖尿病大鼠神经功能评分高于正常血糖组(P<0.01)。相同时间点糖尿病组大鼠脑梗死体积明显大于正常血糖组(P<0.05)。糖尿病组脑梗死区内神经元变性、坏死严重,残存神经元体积缩小,核固缩。结论链脲佐菌素可诱导稳定的糖尿病动物模型,糖尿病加重脑缺血损伤。     

食源性肥胖大鼠2型糖尿病模型的建立

背景：高脂饮食加小剂量链脲佐菌素是目前国内最常用的2型糖尿病大鼠造模方式，但高脂饮食仅能诱导50%大鼠发生胰岛素抵抗，因此还需寻找更理想的2型糖尿病大鼠建模方法。 目的：选择食源性肥胖大鼠进行小剂量链脲佐菌素腹腔注射，建立更理想的2型糖尿病动物模型。 方法：将SD大鼠随机分成对照组和高脂饮食组。4周后，据大鼠体质量将高脂饮食组分为食源性肥胖组和食源性肥胖抵抗组。8周后，所有大鼠均给予小剂量链脲佐菌素(30 mg/kg)腹腔注射，将注射10 d后空腹血糖> 7.8 mmol/L且稳定2周以上者纳为2型糖尿病大鼠模型。检测各组大鼠的空腹血糖、血脂、胰岛素；评价各组大鼠的胰岛素抵抗程度；比较各组大鼠的2型糖尿病成模率。 结果与结论：与对照组及食源性肥胖抵抗组相比，食源性肥胖组大鼠出现明显的体质量增加、高血脂、高胰岛素血症及胰岛素抵抗(P < 0.01)。注射链脲佐菌素后食源性肥胖组2型糖尿病成模率高达100%，食源性肥胖抵抗组成模率仅为12.5%。由结果可知选择食源性肥胖组大鼠作为2型糖尿病造模对象，是2型糖尿病造模方法的成功改良。     

实验性糖尿病大鼠的单纤维肌电图研究

目的:分析链脲佐菌素(STZ)诱导的糖尿病大鼠坐骨神经的神经传导速度和腓肠肌单纤维肌电图的特点,评价两种检查方法对糖尿病多发性神经病早期诊断的价值.方法:健康雄性SD大鼠经腹腔注射STZ60mg穔g-1诱导成1型糖尿病大鼠模型(糖尿病组),在注射STZ后4、6、8、10和12周进行坐骨神经神经传导检查和腓肠肌单纤维肌电...     

糖尿病大鼠皮肤伤口愈合过程中结缔组织生长因子的表达*★

背景：结缔组织生长因子表达在糖尿病伤口愈合过程中的变化及意义少见报道。 目的：观察链脲佐菌素诱导的糖尿病模型大鼠复合创伤修复过程中结缔组织生长因子表达的变化及意义。 方法：将Wistar大鼠随机分成正常对照组和模型组，3周后将各组动物复合背部1.3 cm2全厚皮切除形成伤口。 结果与结论：链脲佐菌素诱发的糖尿病模型大鼠伤口愈合明显延迟，创伤后第4，8，12 和16天创面愈合率明显低于正常对照组(P < 0.01)。术后第8天，糖尿病组大鼠肉芽组织成熟度和新生血管形成指标得分均低于正常对照组(P < 0.01)。正常对照组的结缔组织生长因子蛋白表达呈时间递增趋势，而糖尿病组的结缔组织生长因子表达在整个创面愈合过程的后期(第12天后)均明显低于正常对照组(P < 0.01)。结果提示，糖尿病大鼠皮肤伤口愈合后期创面组织结缔组织生长因子表达相对正常对照组减少可能是导致创面愈合迟缓的重要原因之一。     

依达拉奉对糖尿病周围神经病大鼠神经保护的机制

目的 探讨依达拉奉对糖尿病周围神经病(DPN)大鼠神经保护的机制.方法 采用链脲佐菌素(STZ)一次性腹腔注射诱导建立SD大鼠DPN模型,并随机分为对照组和治疗组(各10只);治疗组给予依达拉奉3 mg/(kg·d)腹腔注射共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);应用酶标法及免疫组化法分别检测坐骨神经半胱氨酸蛋白酶( caspase)-3和Bcl-2表达水平,并与正常组(10只)比较.结果 与正常组比较,对照组大鼠TTT明显升高,MCV和SCV明显减慢,坐骨神经caspase-3和Bcl-2表达水平明显增高(均P＜0.01);与对照组比较,治疗组大鼠TTT明显降低,MCV和SCV明显提高(均P＜0.01);坐骨神经caspase-3表达水平明显降低,Bcl-2表达水平明显增高(均P＜0.05).结论 依达拉奉可以减轻DPN大鼠坐骨神经损伤,其机制可能与其降低周围神经caspase-3表达和增强Bcl-2表达有关.     

糖尿病大鼠脑组织紧密连接蛋白Occludin 表达的变化

目的:研究糖尿病大鼠脑组织紧密连接蛋白Occludin表达的变化.方法:30只雄性SD大鼠随机分为糖尿病1个月组、糖尿病3个月组及正常对照组.腹腔注射链脲佐菌素制作糖尿病大鼠模型,采用逆转录PCR和Western blot法检测大鼠脑组织Occludin mRNA和蛋白的水平.结果:糖尿病1个月组和3个月组大鼠脑组织Occludin mRNA水平[(0.20±0.21),(0.06±0.02)]均较正常对照组(1.00±0.00)显著降低(均P<0.05),且糖尿病3个月组Occludin mRNA水平明显低于糖尿病1个月组(P<0.05).糖尿病1个月组和3个月组大鼠脑组织Occludin蛋白水平[(0.58±0.01),(0.29±0.01)]比正常对照组(1.02±0.06)显著降低(P<0.05-0.01),且糖尿病3个月组Occludin蛋白水平明显低于糖尿病1个月组(P<0.05).结论:糖尿病大鼠脑组织Occludin表达明显降低,并随着病程延长其降低更明显;提示糖尿病使血-脑屏障受到损害.     

Effect of 4-methylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats.

This study examined the effects of 4-methylcatechol (4-MC), a nonamine catechol compound, on the neuropathic process of streptozotocin (STZ)-induced diabetic rats. 4-MC is one of the potent stimulators of nerve growth factor (NGF) synthesis at the cellular level and in cultured sciatic nerve segments of rats. Diabetic rats showed a statistically significant fall in sciatic motor nerve conduction velocity (MNCV) and a significantly reduced NGF content in the sciatic nerve (38.5 +/- 2.8% of control, P less than 0.01) during the experimental period of 4 weeks. 4-MC treatment of the diabetic rats for 4 weeks starting from the STZ injection elevated the NGF content (140% of untreated diabetic rats, P less than 0.05) and prevented the reduction in MNCV, but no effect on high blood glucose levels was seen. These findings suggest that decreased NGF levels in the sciatic nerve of the experimental diabetic rat may be involved in the development of the diabetic neuropathic process and that 4-MC, which can elevate endogenous NGF levels in vivo, may compensate for the inhibitory effect of STZ on the NGF level in progressive diabetic neuropathy.     

Therapeutic Effects of Aldose Reductase Inhibitor on Experimental Diabetic Neuropathy through Synthesis/Secretion of Nerve Growth Factor

We investigated alterations in nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) contents during treatment with epalrestat, an aldose reductase inhibitor (ARI), on streptozotocin (STZ)-induced diabetic neuropathy in rats. Diabetic rats showed a statistically significant reduction in H-wave-related sensory nerve conduction velocity (HSNCV) and in NGF content in sciatic nerves during the experiment of 8 weeks. No reduction in the CNTF content in sciatic nerves was seen in the diabetic rats. The epalrestat treatment, which started 4 weeks after STZ injection, resulted in a significantly greater NGF content and faster HSNCV than those in untreated diabetic rats. But no statistically significant alterations of motor nerve conduction velocity (MNCV) or CNTF content were seen during the treatment. ARI showed the stimulating effect for NGF synthesis/secretion in rat Schwann cell culturein vitro.These findings suggest that decreased levels of NGF in diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy in these rats and further show that epalrestat treatment can be useful for the treatment of diabetic neuropathy through NGF-induction in Schwann cells and/or inhibition of the polyol pathway.     

Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy.

Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin-diabetic rats fed standard or 1% T-supplemented diets for 6 weeks. All measurements were performed in the sciatic nerve. Malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HA) were quantified with N-methyl-2-phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse-phase HPLC, and NGF by ELISA. MDA plus 4-HA concentration (mean +/- SEM) was increased in diabetic rats (0.127 +/- 0.006 vs 0.053 +/- 0.003 micromol/g in controls, P < 0.01), and this increase was partially prevented by T (0.096 +/- 0.004, P < 0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P < 0.05 vs controls). AA levels were decreased in diabetic rats (0.133 +/- 0.015 vs 0.219 +/- 0.023 micromol/g in controls, P < 0.05), and this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P < 0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 +/- 0.16 vs 3.8 +/- 0.1 micromol/g in controls, P < 0.05) and were repleted by T supplementation (4.2 +/- 0.3). NGF levels were decreased in diabetic rats (2.35 +/- 0.20 vs 3.57 +/- 0.20 ng/g in controls, P < 0.01), and this decrease was attenuated by T treatment (3.16 +/- 0.28, P < 0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.     

糖尿病早期大鼠背根神经节中的差异表达基因

目的研究糖尿病早期大鼠背根神经节（dorsal root ganglion,DRG）中基因的差异表达,探索糖尿病神经病变相关基因。方法一次性腹腔注射链脲菌素（streptozotocin,STZ）制备糖尿病模型大鼠,于造模成功后第2周,测量其感觉神经传导速度（sensory nerve conduction velocities,SNCV）,然后运用银染差异显示逆转录聚合酶链反应法（differential display polymerase chain reaction,DD—PCR）从糖尿病模型组与对照组大鼠的DRG中获得两者差异表达的cDNA片段,并进行反杂交筛选、克隆测序、DNA序列检索分析与Northern印迹验证。结果糖尿病模型大鼠建模2周时,其SNCV与对照组相比显著下降（P〈0．05）。银染差异显示并经克隆获得7个差异片段,一个为上调基因,其余为下调基因。经GenBank查询,仅其中的上调基因的cDNA序列与6-丙酮酰四氢喋呤合酶基因（6-pyruvoyl—tetrahydropterin synthase,序列号BC059140）高度同源,其它差异表达片段未检出与已知基因有同源性。结论这些在糖尿病早期背根神经节中差异表达的基因可能参与了糖尿病神经病变的发生发展。     

Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy

Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin‐diabetic rats fed standard or 1% T‐supplemented diets for 6 weeks. All measurements were performed in the sciatic nerve. Malondialdehyde (MDA) plus 4‐hydroxyalkenals (4‐HA) were quantified with N‐methyl‐2‐phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse‐phase HPLC, and NGF by ELISA. MDA plus 4‐HA concentration (mean +/? SEM) was increased in diabetic rats (0.127 +/?0.006 vs 0.053 +/?0.003 mu mol/g in controls, P<0.01), and this increase was partially prevented by T (0.0960.004, P<0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P<0.05 vs controls). AA levels were decreased in diabetic rats (0.133+0.015 vs 0.219 +/?0.023 mu mol/g in controls, P<0.05), and this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P<0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 +/?0.16 vs 3.8 +/?0.1 mu mol/g in controls, P<0.05) and were repleted by T supplementation (4.20.3). NGF levels were decreased in diabetic rats (2.35 +/?0.20 vs 3.57 +/?0.20 ng/g in controls, P<0.01), and this decrease was attenuated by T treatment (3.160.28, P<0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.     

实验性糖尿病大鼠坐骨神经TNF-α表达的动态变化

目的 应用免疫组织化学的方法 研究实验性糖尿病大鼠(DM大鼠)坐骨神经肿瘤坏死因子(tumor necrosis factor-α,TNF-α)的表达变化的动态规律.方法 采用大鼠腹腔内注射链脲菌素(STZ)溶液,制备实验性糖尿病大鼠模型.将80只Wistar大鼠随机分为正常对照组(NC组)、成模即刻(0周)组、成模后4周组、8周组、12周组.应用免疫组织化学的方法 观察TNF-α在大鼠下肢坐骨神经中的动态表达规律.结果 DM各组TNF-α棕黄色异染颗粒在坐骨神经轴索中的表达逐渐减少,与NC组有极显著差异(P<0.01).其中,DM8周组坐骨神经轴索中TNF-α棕黄色异染颗粒减少最明显,分别与DM4周、DM12周组之间有极显著差异(P<0.01).DM各组坐骨神经髓鞘中TNF-α棕黄色异染颗粒逐渐增加,与NC组有极显著差异(P<0.01);DM4周组、8周组、12周组之间相比具有极显著差异(P<0.01).结论 正常生理情况下,TNF-α在大鼠坐骨神经中呈现轴索强阳性表达,髓鞘阴性表达.在糖尿病状态时,TNF-α在轴索的表达逐渐减少,8周时达到高峰.TNF-α在髓鞘的表达随着病程的延长而逐渐增加,这可能是糖尿病的发病机制之一.

Abstract：

Objective To observe the dynamic expression of tumor necrosis factor-α(TNF-α)in the diabetes mellitus(DM)rats'sciatic nerve by immunohistochemistry methods.Methods Streptozocin(STZ)(60mg/kg body weight)intraperitoneal injection was applied to make experimental DM rat models.80 Wistar rats were randomly divided into normal control group(NC group),DM 0w group,DM 4w group,DM 8w group,DM 12w group.Dynamic expressions of TNF-α were observed in the DM rats'sciatic nerve by immunohistochemical methods.Results Since 4w after STZ injection.TNF-α expression in DM group rats'sciatic nerve axon gradually decreased with a peak at 8w.Compared with the NC group,DM 4w,DM8w and DM12w group rats showed significant differences in TNF-α expressions of sciatic nerve axon(P<0.01).Compared with DM 8w group,TNF-α expressions of DM 4w and DM 12w group showed significant differences respectively(P<0.01).Meanwhile,since 4w after STZ injection,TNF-α expression in DM group rats' sciatic nerve myelin sheath gradually increased.Compared with the NC group,DM 4w,DM8w and DMl2w group rats showed significant differences in TNF-α expressions of sciatic nerve myelin sheath(P<0.01).Significant differences were observed among DM 4w,DM 8w or DM 12w group respectively(P<0.01).Conclusion Under normal physiological state,positive TNF-α expression is observed in sciatic nerve axon and negative expression in myelin sheath of DM rats'sciatic nerve.TNF-α expression in axon gradually decreases with a peak at 8w and increases in myelin sheath aggravating with the extension of DM course.It may be a possible mechanism during DM development.     

Expression of neuropeptides in experimental diabetes; effects of treatment with nerve growth factor or brain-derived neurotrophic factor

Rats with streptozotocin-induced diabetes of 4 to 6 weeks duration showed a depletion of both substance P (P < 0.01) and calcitonin gene-related peptide (P < 0.01) in the sciatic nerve. Since expression of both peptides is sensitive to nerve growth factor (NGF) in vitro we examined the effect of treatment of diabetic rats with NGF, which significantly increased the levels of both peptides in treated diabetic animals (P < 0.01 for both). Treatment of non-diabetic rats with a similar NGF regime raised the mean peptide levels to a value similar to that seen in treated diabetic rats but the change was not statistically significant. In vehicle-treated diabetic rats the depletions of sciatic nerve neuropeptides were accompanied by a significant (P < 0.05) reduction in the level of CGRP mRNA in the 4th and 5th lumbar dorsal root ganglia, this was accompanied by an analogous reduction in the mRNA for γ-preprotachykinin A (γ-PPT), which did not attain statistical significance. Treatment of diabetic rats with NGF also prevented the deficits in the levels of CGRP and γ-PPT mRNA in the lumbar dorsal root ganglia (P < 0.05). Treatment of other diabetic rats with the related neurotrophin, brain-derived neurotrophic factor (BDNF), had no effect on the levels of substance P and calcitonin gene-related peptide in the sciatic nerve.     

Depletion of taurine in experimental diabetic neuropathy: implications for nerve metabolic, vascular, and functional deficits

In diabetes, increased oxidative stress, disruption of signal transduction pathways, and endothelial dysfunction have been critically implicated in the pathogenesis of experimental diabetic neuropathy (EDN). The development of nerve conduction slowing in diabetes is accompanied by depletion of the beta-amino acid taurine. Since taurine functions as an antioxidant, calcium modulator, and vasodilator, taurine depletion may provide a pathogenetic link between nerve metabolic, vascular, and functional deficits complicating diabetes. The mechanism(s) of nerve taurine depletion, the localization of critical taurine deficits, and its pathophysiological significance in EDN are however unknown. This study explored the pathophysiological effects of selective nerve taurine replacement in streptozotocin-diabetic (STZ-D) rats. A polyclonal human taurine transporter (TT) antibody was also generated in order to determine potential loci of critical taurine depletion. Two weeks of STZ-D reduced sciatic motor nerve conduction velocity (NCV) by 23% (P < 0.01), decreased composite nerve blood flow by 38% (P < 0.01), and reduced nerve taurine content by 29% (P < 0.05). In STZ-D rats, a 1% taurine diet corrected nerve taurine depletion, prevented motor NCV slowing, and partially attenuated composite nerve blood flow deficits. After 6 weeks of STZ-D, a 1% taurine diet ameliorated motor NCV slowing and endoneurial nutritive blood flow deficits, prevented digital sensory NCV slowing, and reduced ouabain-sensitive nerve (Na,K)-ATPase activity. Immunohistochemical studies localized taurine and the TT to the vascular endothelium and Schwann cells of the sciatic nerve. In conclusion, taurine depletion in the vascular endothelium and Schwann cells of the sciatic nerve may contribute to the neurovascular and metabolic deficits in EDN.     

Naringenin neutralises oxidative stress and nerve growth factor discrepancy in experimental diabetic neuropathy

Abstract

Objectives:

Present study aims to investigate the ameliorative effects of naringenin (NG) on experimentally induced diabetic neuropathy (DN) in rats.

Methods:

Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ, 60?mg/kg). Naringenin (25 and 50?mg/kg/day) treatment was started 2?weeks after the diabetes induction and continued for five consecutive weeks. Pain threshold behaviour tests were performed at the end of the treatment. Serum levels of glucose, insulin and pro-inflammatory cytokines were assessed. In sciatic tissues, markers oxidative stress, cytokines and neurotrophic factors were measured.

Results:

NG treatments showed significant decrease in paw-withdrawal (P?<?0.01) and tail-flick latency (P?<?0.01). The drug attenuated the diabetic-induced changes in serum glucose, insulin and pro-inflammatory cytokines including tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). In sciatic nerve, the diabetic-induced alterations in interleukins and oxidative stress biomarkers were significantly attenuated by NG. Decreased sciatic expressions of insulin growth factor (IGF) and nerve growth factor (NGF) in diabetic rats were also ameliorated by NG. Diabetes-induced dysregulated levels of nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were ameliorated by NG. Histological analysis showed that NG corrected the altered sciatic changes in diabetic animals.

Discussion:

We suggest that neuro-protective effect of NG molecules in sciatic nerve of diabetic rats, through its anti-diabetic as well as antioxidant and anti-inflammatory properties.