摘要
目的研究葡萄糖原合酶-3β（glycogensynthasekidnase 3β，GSK-3β）抑制剂4-benzyl-2-methyl-1，2，4-thiadiazolidine-3，5-dione（TDZD-8）对一氧化碳（carbonmonoxide，CO）中毒大鼠迟发性脑病（delayedneuropsychologicalsequelae，DNS）发生率、神经细胞形态学以及Tau蛋白过度磷酸化的影响。方法大鼠经Morris水迷宫训练l周后随机数字表法随机选取10只作为空白对照组（Con组）。余大鼠采用腹腔注射CO气体建立急性CO中毒模型（染毒），将存活大鼠采用随机数字表法分为CO中毒模型组（Mod组）、TDZD-8低剂量组（TL组）、TDZD-8中剂量组（TM组）、TDZD-8高剂量组（TH组），每组10只。各组大鼠均接受6d高压氧治疗。染毒后15d应用Morris水迷宫筛选DNS大鼠。于染毒后21d灌注固定取脑组织，采用苏木精伊红（hematoxylin-eosin，HE）染色检测脑组织病理学变化，免疫组化检测脑组织Tau蛋白磷酸化。结果Mod组大鼠逃避潜伏期（39．7＋20．5）s较Con组（11．0±3．5）s显著延长（P〈0．05），DNS发生率高达70％，脑组织病理损害明显，皮质及海马P-tau（Serl99）阳性细胞较Con组明显增多（P〈0．05）。TDZD-8各干预组较Mod组逃避潜伏期缩短，DNS发生率下降，脑组织病理损害减轻，皮质及海马P-tau（Serl99）阳性细胞减少，但仅TM组与Mod组比较，差异有统计学意义（P〈0．05）。DNS大鼠较非DNS大鼠皮质及海马P-tau（Serl99）阳性细胞明显增多。结论Tau蛋白过度磷酸化可能参与了CO中毒大鼠DNS的病理过程。TDZD-8对大鼠CO中毒DNS脑损伤具有保护作用。
Objective To determine the effects of 4-benzyl-2-methy-l,2,4-thiadiazolidine-3,5-dione（TDZD-8）, inhibitor of glycogen synthase kidnase 3[3 （GSK-3β）, on the expression of Tau protein hyperphosphorylation, pathological change in neuron and incidence of delayed neuropsychologieal sequelae（DNS） after carbon monoxide（CO） poisoning. Methods Ten rats were randomly chosen for control group（Con group） after one week Morris water maze training. CO poisoning model was established with introducing CO into abdominal cavity. The survival rats were randomly divided into four groups with 10 rats each group： CO poisoning group （Mod group） and low-dose group （0.5 mg/kg）（TL group）, middle-dose group（1.0 mg/kg）（TM group） and high-dose group（ 1.5 mg·kg）（TH group） of TDZD-8. All rats received hyperbaric oxygen therapy for six days. Morris water maze was adopted 15 d after CO poisoning to identify DNS happening. The pathological change was observed by hematoxylin and eosin staining. The expression of hyperphosphorylated Tau protein was determined by immunohistochemical staining. Results The escape latency in Mod group （39.7±20.5） s was longer than that in Con group （11.0±3.5） s （P〈0.05）. Incidence of DNS in Mod group reached 70%. Significant brain tissue pathological damage can be seen in Mod group, which showed more P-tau （Ser199） positive cells in cortex and hippocampus than those in Con group （P〈0.05）. Compared with Mod group, the escape latency, brain tissue pathological damage, incidence of DNS and expression of P-tau （Ser199） positive cells in TDZD-8 intervention group were improved. However significant differences only be found between TM group and Mod group （P〈0.05）. There were more P-tau （Ser199） positive cells in cortex and hippocampus in DNS rats than those in non-DNS rats（P〈0.05 ）. Conclusions Tau protein hyperphosphorylation may be involved in the pathological process of DNS after CO poisoning. TDZD-8 had a protective effect t
出处
《国际麻醉学与复苏杂志》
CAS
2015年第3期234-238,共5页
International Journal of Anesthesiology and Resuscitation
基金
徐州市社会发展基金（XM138059）
徐州医学院附属医院优秀学科带头人培养对象基金（2011109062）
关键词
一氧化碳中毒
迟发性脑病
TDZD-8
TAU蛋白
Carbon monoxide poisoning
Delayed neuropsychologic sequelae
4-benzyl-2-methyl-l, 2,4-thiadiazolidine-3,5-dione
Tau protein
