Mer受体酪氨酸激酶与SD大鼠糖尿病周围神经病变的相关性  

Correlation between Mer receptor tyrosine kinase and diabetic peripheral neuropathy in Sprague-Dawley rats

作　　者：苏晓杨 陈文婷 付怡丹 赵燕[1] 兰丹凤 杨秋萍[1] Su Xiaoyang;Chen Wenting;Fu Yidan;Zhao Yan;Lan Danfeng;Yang Qiuping(Yunnan Province Clinical Research Center for Metabolic diseases,First Affiliated Hospital of Kunming Medical University,Kunming 650032,Yunnan Province,China;The First People’s Hospital of Yunnan Province,Kunming 650100,Yunnan Province,China)

机构地区：[1]昆明医科大学第一附属医院云南省代谢性疾病临床医学研究中心,云南省昆明市650032 [2]云南省第一人民医院,云南省昆明市650100

出　　处：《中国组织工程研究》2025年第8期1593-1599,共7页Chinese Journal of Tissue Engineering Research

基　　金：云南省科技厅科技计划项目(202001AY070001-159),项目负责人:杨秋萍。

摘　　要：背景:糖尿病周围神经病变的发病机制目前尚未明确,TAM(Tyro3、Axl和MerTK)受体酪氨酸激酶具有控制中枢神经系统凋亡细胞和抑制炎症反应的作用。目的:探讨2型糖尿病及其周围神经病变SD大鼠血浆及坐骨神经组织Mer受体酪氨酸激酶水平的差异,研究Mer受体酪氨酸激酶与糖尿病周围神经病变的关联性。方法:40只雄性SD大鼠随机分为对照组15只、2型糖尿病组10只及2型糖尿病周围神经病变组15只。对照组大鼠喂普通饲料,实验组大鼠行高脂高糖饮食6周,并腹腔内注射单剂量小剂量链脲佐菌素35 mg/kg,14 d尾静脉取血检测血糖≥16.7 mmol/L为2型糖尿病造模成功。周围神经病变组大鼠动物继续高糖、高脂喂养8周。麻醉后活体分离检测大鼠坐骨神经传导速度,腹主动脉取血,取坐骨神经组织。光镜下观察各组神经纤维组织学改变,确认糖尿病周围神经病变造模成功。ELISA检测大鼠外周血血糖、血脂及血清MerTK水平,苏木精-伊红染色观察坐骨神经组织学改变;免疫荧光、免疫组化及免疫蛋白印迹检测坐骨神经组织中MerTK的表达。结果与结论:①实验成功构建SD大鼠2型糖尿病及2型糖尿病周围神经病变大鼠模型,糖尿病周围神经病变成模率80%;与对照组比较,2型糖尿病及糖尿病周围神经病变组大鼠血糖水平显著升高(P<0.0001),糖尿病周围神经病变组高于2型糖尿病组;坐骨神经传导速度明显下降(P<0.05),糖尿病周围神经病变组低于2型糖尿病组。②组织学检查:与对照组相比,2型糖尿病组大鼠坐骨神经核减少,有部分空泡变性,出现吞噬细胞;糖尿病周围神经病变组胞体肿胀,核间距增大,出现空泡变性,髓鞘周围出现隔断、不平滑,轴索变为网格状。③血清中MerTK水平:糖尿病周围神经病变组显著高于对照组(P<0.05)。④坐骨神经组织中MerTK的表达:与对照组比较,糖尿病周围神经病变组中明显上调(BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system.OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy.METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue.RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modelin

关 键 词：Mer受体酪氨酸激酶 糖尿病周围神经病变 生物学标记物 2型糖尿病 SD大鼠 

分 类 号：R496[医药卫生—康复医学] R318[医药卫生—临床医学] R446