山莨菪碱对大鼠横纹肌溶解致急性肾损伤时内质网应激的影响-内科学专业论文.docxVIP

解放军医学院硕士学位论文 解放军医学院硕士学位论文 目 录 中文摘要 ············································································ 1 英文摘要 ············································································ 3 前 言 ············································································ 5 正 文 ············································································ 7 材 料 ············································································ 7 方 法 ············································································ 9 结 果 ·········································································· 12 讨 论 ·········································································· 16 结 论 ·········································································· 18 附 图 ·········································································· 19 参考文献 ·········································································· 27 文献综述 内质网应激与肾脏疾病 ········································· 29 附 录 英文缩略词表 ····················································· 39 攻读学位期间发表文章情况 ·················································· 41 致 谢 ·········································································· 43 解放军医学院硕士学位论文 解放军医学院硕士学位论文 解放军医学院硕士学位论文 解放军医学院硕士学位论文 - - PAGE 10 - 作 者：赵 维 学科专业：内科学 导 师：吴广礼 山莨菪碱对大鼠横纹肌溶解致急性肾损伤时内质网应激的影响 中文摘要 背景与目的 本课题组以往研究表明，过度训练可导致大鼠横纹肌溶解，进 而导致急性肾损伤(AKI)，其中细胞凋亡机制发挥着重要作用，山莨菪碱可通过抑 制细胞凋亡发挥肾保护作用，而山莨菪碱抗凋亡的具体作用机制值得探讨。研究 表明，当细胞暴露于缺氧、营养缺乏、氧化应激、蛋白质异常糖基化反应以及钙 稳态失衡等因素时，会导致内质网内未折叠或误折叠蛋白质蓄积，诱发内质网应 激(ERS)。ERS 是细胞的一种自我保护机制，但过强或持续时间过长的 ERS 可引起 细胞凋亡。ERS 介导的细胞凋亡参与了急性肾损伤的病理生理过程，山莨菪碱抗 凋亡机制是否与 ERS 有关尚不清楚。本研究拟评价山莨菪碱对大鼠横纹肌溶解致 急性肾损伤时 ERS 的影响，以探讨其抗凋亡的机制，为临床研究提供参考。 方法 雄性 SD 大鼠 42 只，体重 200~220 g，采用随机数字表法将其分为 3 组：对照组（C 组, n=6），双侧后肢肌肉注射生理盐水 10 ml/kg；急性肾损伤组（AKI 组, n=18），双侧后肢肌肉注射 50% (v/v)甘油 10 ml/kg；山莨菪碱组（AD 组, n=18）， 腹腔注射山莨菪碱 10 mg/kg，20 min 后处理同 AKI 组。C 组于肌肉注射生理盐水 后即刻(T0)，AKI 组和 AD 组于甘油给药后 1 h(T1)、6 h(T2)、24 h(T3)分别随机取 6 只大鼠，抽取静脉血样测定血浆尿素氮(BUN)、