衰老大鼠术后认知功能障碍模型构建以及金钗石斛对该模型大鼠治疗效果评价
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国家自然科学基金项目(82160223);贵州省中医药管理局中医药、民族医药科学技术研究课题(QZYY-2021-111);遵义市科技计划项目[遵义市科合HZ字(2022)391号]


Establishment of postoperative cognitive dysfunction model in aging rats and evaluation of the therapeutic effect of Dendrobium nobile on the model rats
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    摘要:

    目的 构建衰老大鼠术后认知功能障碍(POCD)模型,并利用胃灌金钗石斛评价其对该模型治疗效果。方法 选取30只4月龄的SD大鼠,通过在其颈背部皮下注射10% D - 半乳糖的方式构建衰老大鼠模型。注射剂量设定为0.125 g·kg-1·d-1,连续注射42 d。将成功构建的衰老大鼠随机分为对照组、POCD组和POCD治疗组,每组10只。POCD组与POCD治疗组在3.2%七氟烷吸入麻醉的条件下实施左肾切除术,以此来建立衰老大鼠POCD模型,而对照组的大鼠则不进行任何处理。待大鼠麻醉苏醒2 h后,对POCD治疗组按照10 g·kg-1·d-1 的剂量进行金钗石斛汤剂灌胃处理,对照组和POCD组则给予等体积的生理盐水灌胃,灌胃操作持续进行14 d。运用Morris水迷宫实验对各组大鼠的学习记忆能力展开评估;平衡木实验评价各组大鼠平衡能力和运动协调能力;ELISA法检测血清中神经元特异性烯醇化酶(NSE)、S-100β含量;HE染色观察大鼠海马神经元细胞的形态变化。结果 水迷宫实验中,与对照组和POCD治疗组相比,POCD组的衰老大鼠在第三象限的滞留时间以及有效进入平台的次数均显著减少,差异有统计学意义(P<0.05);平衡木实验中,与对照组及POCD治疗组比较,POCD组衰老大鼠的始动时间、过杆时间明显延长,差异均有统计学意义(P<0.05)。ELISA结果显示,与对照组及POCD治疗组比较,POCD组衰老大鼠血清NSE、S-100β含量明显升高,差异均有统计学意义(P<0.05)。HE染色结果提示,POCD组海马神经元出现明显病理改变,其细胞结构层次模糊,排列既紊乱又松散,细胞数量显著减少,细胞形态失去规则性,细胞核发生固缩现象,染色程度较深,细胞质边界不清晰;POCD治疗组大鼠的海马组织虽已产生病理性改变,但病变程度较POCD组更轻。结论 采用“10% D-半乳糖0.125 g·kg-1·d-1连续42 d注射于4月龄SD大鼠颈背部皮下构建的衰老大鼠,在3.2%七氟烷吸入麻醉下行左肾切除术”的多因素复合造模法可成功构建衰老大鼠POCD模型,通过中药金钗石槲治疗后,该模型大鼠的认知功能可得到改善,此方法可为今后研究利用我国传统医药治疗POCD提供可靠动物模型

    Abstract:

    Objective To establish a postoperative cognitive dysfunction(POCD) model in aging rats and evaluate the model's quality through intragastric administration of Dendrobium nobile extract. Methods Thirty 4-month-old SD rats were selected to construct an aging rat model by subcutaneous injection of 10 % D-galactose in their neck and back. The injection dose was set to 0.125 g·kg-1·d-1 for 42 consecutive days. The successfully constructed aging rats were randomly divided into three groups: control group, POCD group and POCD treatment group, with 10 rats in each group. The POCD group and the POCD treatment group underwent unilateral nephrectomy under the condition of 3.2 % sevoflurane anesthesia to establish a POCD model in aging rats, while the rats in the control group did not undergo any treatment. After 2 hours of recovery from anesthesia, the POCD treatment group was treated with Dendrobium nobile decoction at a dose of 10 g·kg -1·d -1. The control group and the POCD group were given an equal volume of normal saline, and the gavage operation continued for 14 days. Morris water maze experiment was employed to gauge the learning and memory faculties of rats in every group. Balance beam experiment was carried out to gauge the balance and motor coordination aptitudes of rats in each respective group. The contents of NSE and S-100β in serum were detected by ELISA. HE staining was utilized to observe the morphological alterations of hippocampal neurons in rats. Results In the water maze experiment, the POCD group exhibited a marked decrease in both the duration of retention in the third quadrant and the frequency of effective platform entries, when compared with the control group and the POCD treatment group, and the statistical significance of this difference was evident(P<0.05). In the balance beam experiment, when compared to the control group and the POCD treatment group, the aging rats in the POCD group exhibited a significant prolongation in both the starting time and the time taken to cross the beam, and this disparity was statistically significant(P<0.05). ELISA results indicated that, in comparison with the control group and the POCD treatment group, the aging rats in the POCD group had a significant increase in serum NSE and S - 100β levels, and the statistical significance of this difference was evident(P<0.05). HE staining results revealed that the hippocampal neurons in the POCD group presented distinct pathological alterations. The cellular structure was indistinct, with a chaotic and loose arrangement. There was a marked decrease in the number of cells. The cell morphology was irregular, and the nuclei were pyknotic, exhibiting a high-intensity staining. Additionally, the cytoplasmic boundaries were unclear.Conclusion The aging rat POCD model was successfully established by using the multifactorial method of ‘10% D-galactose 0.125 g·kg -1·d -1 subcutaneously injected into the neck and back of the 4-month-old SD rats for 42 days and unilateral nephrectomy under 3.2% sevoflurane anesthesia’, this method can provide a reliable animal model for the future research of using our traditional medicine to treat POCD

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蒋瑞,张乃心,赵楠,等.衰老大鼠术后认知功能障碍模型构建以及金钗石斛对该模型大鼠治疗效果评价[J].西部医学,2025,37(10):1438-1444,1450.

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  • 在线发布日期: 2025-10-20
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