竹荪多糖对慢性酒精暴露诱导的大鼠认知功能障碍的影响

Effects of Dictyophora polysaccharides on cognitive dysfunction induced by chronic alcohol exposure in rats

摘要

目的 探讨竹荪多糖（dictyophora polysaccharides，DIP）对慢性酒精所致大鼠认知功能障碍的影响。 方法 60只雄性SD大鼠随机分为5组（n=12）：空白对照组（Control，生理盐水），单纯DIP处理组［DIP_H，300 mg/（kg·d）DIP连续灌胃28 d］，单纯酒精组［EtOH，10 mg/（kg·d）60%酒精连续灌胃28 d］，竹荪多糖低剂量干预组［EtOH+DIP_L，10 mg/（kg·d）60%酒精+100 mg/（kg·d）DIP灌胃，中间间隔6 h，连续28 d］，竹荪多糖高剂量干预组［EtOH+DIP_H，10 mg/（kg·d）60%酒精+300 mg/（kg·d）DIP灌胃，中间间隔6 h，连续28 d］，灌胃至第25天进行4 d的水迷宫训练，第29天行水迷宫测试检测大鼠记忆、学习功能情况，苏木精-伊红染色评估肝及脑组织水肿和炎症情况，免疫组织化学染色检测脑组织炎症细胞及髓鞘碱性蛋白（myelin basic protein，MBP）的表达情况，免疫印迹检测海马组织髓鞘相关蛋白2，2-环核苷酸-3-磷酸二酯酶（2，2-Cyclic Nucleotide-3-Phosphodiesterase，CNP）表达量，髓鞘染色（luxoL fast blue，LFB染色）及髓鞘透射电镜观察大鼠髓鞘结构完整性。 结果 与Control组相比，EtOH组逃避潜伏期明显增加，MBP表达量减少，髓鞘密度明显减少。DIP干预可改善大鼠认知功能障碍，增加MBP及CNP的表达及减少髓鞘的损伤情况。 结论 在300 mg/kg剂量下，DIP可能通过保护髓鞘的结构和功能完整性来改善慢性酒精暴露诱导的认知功能缺陷。

Abstract

Objective To investigate the effects of dictyophora polysaccharides（DIP） on cognitive dysfunction induced by chronic alcohol exposure in rats. Methods Sixty male Sprague-Dawley（SD） rats were randomly divided into five groups（n=12）：control group （normal saline），DIP group［DIP_H，DIP administered by gavage at 300 mg/（kg·d） for 28 consecutive days］，alcohol group［EtOH，60% alcohol administered by gavage at 10 mg/（kg·d） for 28 consecutive days］，low-dose DIP treatment group［EtOH+DIP_L，60% alcohol administered at 10 mg/（kg·d） and DIP administered at 100 mg/（kg·d） by gavage，with an interval of 6 hours between doses，for 28 consecutive days］，and high-dose DIP treatment group［EtOH+DIP_H，60% alcohol administered at 10 mg/（kg·d） and DIP administered at 300 mg/（kg·d） by gavage，with an interval of 6 hours between doses，for 28 consecutive days］. On day 25 of gavage，water maze training was provided for the rats for 4 days. On day 29，a water maze test was performed to determine the memory and learning functions of the rats；HE staining was used to evaluate the edema and inflammation of the liver and brain tissues； presence of inflammatory cells and the expression of myelin basic protein（MBP） in brain tissue were measured using immunohistochemical staining； Western blot was used to measure the expression of 2，2-cyclic nucleotide-3-phosphodiesterase（CNP） in the hippocampal tissue；the structural integrity of the myelin sheath was evaluated using LuxoL fast blue（LFB） staining and transmission electron microscopy. Results Compared with the control group，the EtOH group showed a significantly increased escape latency，reduced expression of MBP，and decreased density of the myelin sheath. DIP intervention significantly improved cognitive dysfunction in rats，increased the expression of MBP and CNP，and reduced myelin damage. Conclusion At a dose of 300 mg/kg，DIP may ameliorate cognitive dysfunction induced by chronic alcohol exposure by protecting the structural and functional integrity of myelin sheaths.

关键词

慢性酒精暴露 / 竹荪多糖 / 认知功能 / 海马 / 髓鞘

Key words

chronic alcohol exposure / dictyophora polysaccharides / cognitive function / hippocampus / myelin sheath

基金资助

国家自然科学基金资助项目(82060340)