雷公藤毒素对七氟醚麻醉后糖尿病大鼠学习记忆的影响
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The effect of celastrol on learning and memory in diabetic rats after sevoflurane inhalation
背景
本研究的目的是设计一个可见于老年性痴呆患者的一些神经病理学改变的动物模型，并观察雷公藤毒素对该模型认知神经病理学的影响。
方 法
40只雄性SD大鼠，体重300-350g，随机分为5组（n = 8）：对照组（Con）; 七氟醚组（Sev）; 糖尿病组（DM）; 糖尿病+七氟醚组（DM / Sev）; 糖尿病+七氟醚+雷公藤红素组（Cel）。通过腹膜内注射链脲霉素（STZ）诱导糖尿病。20天后，Sev，DM / Sev和Cel组大鼠吸入3％七氟醚2小时，而对照组和DM组则吸入空气。Cel组大鼠每天腹腔注射雷公藤毒素（0.7mg / kg）持续4天，而对照组腹腔内注射等体积的二甲基亚砜。使用Morris水迷宫试验来检测认知功能。最后一次水迷宫试验完成后杀死大鼠，用刚果红染色观察海马中淀粉样物质的沉积。并用免疫组织化学法检测海马中GFAP和IGF-1的表达。
结 果
糖尿病降低认知功能，使淀粉样物质沉积和GFAP表达增加，并减少海马中IGF-1的表达（所有p值<0.05）。七氟醚麻醉可增强该变化但雷公藤毒素可抑制该变化（所有p值<0.05）。
结 论
Sev / DM组大鼠的认知功能和神经化学变化与老年痴呆症患者相似。雷公藤毒素可抑制这些变化并应进一步评估其作为治疗痴呆症患者临床药物的可能性。
原始文献摘要
Abstract
Introduction: The aim was to devise an animal model showing some of the neuropathological changes seen in senile dementia, and to investigate the effect of celastrol on cognition neuropathology in this model.
Material and methods: Forty male Sprague Dawley rats weighing 300–350 g were randomly divided into 5 groups (n = 8 each): control (Con); inhaled sevoflurane (Sev); diabetes mellitus (DM); diabetes mellitus + inhaled sevoflurane (DM/Sev); diabetes + inhaled sevoflurane + celastrol (Cel). Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). After 20 days, the Sev, DM/Sev and Cel group rats inhaled 3% sevoflurane for 2 h,while the control and DM groups inhaled air. Cel group rats were given intraperitoneal injections of celastrol (0.7 mg/kg) daily for 4 days, while the control group received intraperitoneal injections of an equal volume of dimethylsulfoxide. The Morris water maze test was performed to test cognition. Animals were killed after the last water maze test and Congo red staining was used to observe deposition of amyloid substance in the hippocampus. The expression of GFAP and IGF-1 in the hippocampus was observed by immunohistochemistry.
Results: Diabetes decreased cognition, increased amyloid substance and GFAP expression, and decreased IGF-1 expression in the hippocampus(all p-values < 0.05). Sevoflurane administration intensified and celastrol decreased these changes (all p-values < 0.05).
Conclusions: Sev/DM rats showed cognitive and neurochemical changes similar to those seen in senile dementia. Celastrol decreased these changes and should be evaluated further as a possible clinical agent in dementia.
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