TSP-1 expression changes in diabetic rats with spinal cord injury
TSP-1 expression changes in diabetic rats with spinal cord injury
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DOI：
10.1179/174313209x403887
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发表时间：
2009-03
影响因子：
1.9
通讯作者：
Zhenghua Hong;Hai‐xiao Chen;Huaxing Hong;Lie Lin;Zhangfu Wang
中科院分区：
文献类型：
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作者：
Zhenghua Hong;Hai‐xiao Chen;Huaxing Hong;Lie Lin;Zhangfu Wang
摘要目的：脊髓损伤(SCI)是世界范围内发病率和死亡率较高的疾病，尤其是合并糖尿病的患者。凝血酶敏感蛋白1(TSP-1)是一种相互激活因子，可在高血糖时引起神经元损伤。我们在糖尿病大鼠模型中研究了TSP-1在脊髓损伤发生中的作用。方法：雌性SD大鼠30只，随机分为3组：脊髓损伤组、脊髓损伤+糖尿病组和假手术组。10只大鼠腹腔注射链脲佐菌素(60 mg/kg)复制糖尿病模型，其余20只大鼠注射生理盐水为脊髓损伤组，第三组为假手术组。4周后，脊髓损伤组大鼠10只，糖尿病大鼠10只，用冲击器造成脊髓损伤，假手术组也在相同时间段无脊髓损伤。于脊髓损伤后12h处死动物，进行免疫组织化学和免疫印迹分析TSP-1蛋白的表达。苏木精-伊红染色观察3组大鼠脊髓的形态变化。所有数据采用t检验。结果：造模前三组大鼠体重、血糖均无明显差异。糖尿病诱导4周后，SCI组与SCI+糖尿病组体重、血糖差异有统计学意义。免疫组织化学和Western印迹分析显示，脊髓损伤组TSP-1表达高于假手术组，但低于脊髓损伤+糖尿病组(p<；0.01)。脊髓损伤组，尤其是脊髓损伤+糖尿病组损伤脊髓的病理改变非常明显，表现为中央核心病变，周围有备用的边缘组织，多变的囊变和胶质细胞的形成。讨论：我们的工作提供了实验证据，在糖尿病大鼠损伤后12小时的脊髓损伤节段可以检测到TSP-1的高表达。它可能导致糖尿病大鼠脊髓损伤后的严重损害。
Abstract Objectives: Spinal cord injury (SCI) is associated with high morbidity and mortality worldwide, especially in patients with diabetes mellitus. Thrombospondin 1 (TSP-1) is a mutual activator and can cause neuron injury during hyperglycemia. We investigated the role of TSP-1 in a model of diabetic rats in the development of SCI. Methods: Thirty Sprague–Dawley female rats were divided into three groups (SCI group, SCI + diabetes group and sham-operated group) at random. Ten rats were intraperitoneally injected with streptozocin (60 mg/kg) to induce diabetes; the remaining 20 rats received an injection of 0.9% saline as SCI group and the third group was sham-operated group. Four weeks later, ten rats in the SCI group and ten diabetic rats were subjected to SCI using an impactor, and the sham-operated group was also followed at the same time course without SCI. These animals were killed at 12 hours after SCI for immunochemistry and Western blot analysis of the injured section for the expression of TSP-1 protein. Morphological changes of spinal cord in three groups also were observed through hematoxylin–eosin staining. All data were analysed by t-test. Results: The data of weight and blood sugar indicated no significant difference in all three groups before animal model induction. Four weeks after the induction of diabetes, the differences between the SCI and SCI + diabetes groups in weight and blood sugar were distinct. Immunochemistry and Western blot analysis showed increased TSP-1 expression in SCI group when compared with the sham-operated group rat but less than the SCI + diabetes group (p<0.01). The pathological alterations, such as central core lesion with a spare peripheral rim of tissue, and variable cyst formations and gliosis were very apparent in the damaged spinal cord area in the SCI group and especially in the SCI + diabetes group. Discussion: Our work provides experimental evidence that the elevated expression of TSP-1 can be detected in the injured segment of the spinal cord at 12 hours after injury in diabetic rats. It may contribute to severe damage in diabetic rats after SCI.