摘要
目的观察通络方剂对糖尿病大鼠海马组织氧化应激水平及超微结构的影响,探讨糖尿病脑病的可能发病机制。方法通过腹腔注射链脲佐菌素(60mg/kg)制作糖尿病大鼠模型,72h后测定尾静脉末梢血糖≥16.7mmol/L为诱导糖尿病模型成功。将造模成功的大鼠分成糖尿病通络方剂干预组(DM+TLR组,予通络方剂0.4g·kg-1.d-1)和糖尿病未干预组(DM组)。DM组和正常对照组(CON组)每日均在同一时间以同等剂量蒸馏水一次性灌胃。12周后测定糖尿病大鼠血浆和海马组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和脂质过氧化产物丙二醛(MDA)含量,并用电子显微镜观察海马神经元超微结构的变化。结果与CON组比较,DM组和DM+TLR组大鼠体重显著减轻(P值均<0.01),血糖和糖化血红蛋白(HbA1c)显著升高(P值均<0.01)。DM组大鼠发病12周时海马组织神经元细胞质内空泡形成明显,细胞膜与周围分界不清,细胞核内染色质边集,电子密度增加,部分线粒体肿胀,嵴大部分消失,基质呈空泡状,粗面内质网腔有不同程度的扩张,出现脱颗粒;DM+TLR组神经元形态接近正常,细胞质内空泡形成明显减少,线粒体嵴变短,仍有部分排列紊乱,局部粗面内质网腔轻微扩张,但较DM组明显减轻。与CON组比较,DM组和DM+TLR组大鼠在观察终点血浆和海马组织内SOD、GSH-Px水平均显著降低(P值分别<0.01、0.05),MDA水平则显著升高(P值分别<0.01、0.05);与DM组比较,DM+TLR组血浆和海马组织内SOD、GSH-Px活性显著增加(P值均<0.01),MDA水平显著降低(P值分别<0.01、0.05)。结论通络方剂可以改善糖尿病大鼠海马组织氧化应激水平及超微结构,可能是通过减少自由基生成及提高抗氧化酶活性实现的。
Objective To investigate the effects of Tongluo Recipe（TLR） on oxidative stress and ultrastructure of the hippocampus in streptozotocin-induced diabetic rats. Methods Diabetes was induced by a single intraperitoneal injection of streptozotocin （ 60 mg/kg） dissolved in citrate buffer. The streptozotocin-injected rats with blood glucose levels ≥16.7 mmol/L 3 days after injection were included in the study and were randomly divided into two groups： an untreated diabetic group and TLR treatment group. Rats in TLR treatment group received 0.4 g· k^g-1·d^-1 TLR treatment throughout the experiment. Rats in the untreated diabetic group and normal control group were given gastric perfusion of distilled water once at the same time and dose. After 12 weeks of treatment, superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were measured in hippocampal tissues and plasma. The cellular ultrastructure of neurons in the hippocampus was observed through transmission electronic microscope. Results MDA levels were increased, GSH-Px and SOD activities were decreased in the plasma （ P〈 0. 001 ） and hippocampus （ P〈 0.01 ） of untreated diabetic group compared to the controls. In untreated diabetic group, conspicuous intracytoplasmic vacuole formation was present in neurons in diabetic rat hippocampus; mitochondriales crista disappeared, some ribosomal particles became diffusely dispersed, and the nucleus became shrunken. TLR obviously ameliorated the morphological changes and improved SOD and GSH-Px activity. In TLR treatment group, the levels of GSH-Px and SOD were significantly increased and the levels of MDA were decreased in the plasma （P〈 0.001 ） and hippocampus （P〈 0.05） compared to those of the diabetic rats. Conclusion TLR can improve the ultrastructure and oxidative stress level, probably through depleting free radical production and increasing activities of antioxidatant. （Shanghai Med J, 2009, 32： 406-409）
出处
《上海医学》
CAS
CSCD
北大核心
2009年第5期406-409,I0002,共5页
Shanghai Medical Journal
基金
国家重点基础研究规划("973"计划
2005CB523304)资助项目
关键词
糖尿病脑病
海马
氧化应激
超微结构
Diabetic encephalopathy
Hippocampus
Oxidative stress
Ultrastructure
