目的探索淫羊藿次苷Ⅱ(ICSⅡ)对链脲佐菌素(STZ)所致大鼠学习记忆减退的作用及机制。方法雄性SD大鼠随机分为假手术组,模型组,ICSⅡ低、高剂量组(均n=10)。模型组和ICSⅡ组大鼠在第1日和第3日双侧侧脑室注射STZ 5μL(1.5 mg·kg~(-1))模拟散发性老年性痴呆,假手术组注入等体积柠檬酸缓冲液。第二次手术后开始给药,ICSⅡ低、高剂量组每日灌胃ICSⅡ3、10 mg·kg~(-1),假手术组和模型组给予等体积双蒸水,连续给药21 d。给药后第16日开始进行为期6 d的Morris水迷宫实验检测大鼠行为学功能。水迷宫实验结束后,通过Western blot实验技术检测大鼠海马组织中自噬基因Beclin 1、微管相关蛋白1轻链3(LC3)Ⅰ和LC3Ⅱ的蛋白表达以及β-淀粉样蛋白(Aβ1-42)的含量。结果水迷宫实验中模型组较假手术组大鼠的平均逃避潜伏期明显延长,穿越目标象限次数显著减少(P<0.05);海马组织中Aβ1-42的含量显著增加(P<0.05),Beclin 1表达明显减少(P<0.05),LC3-Ⅱ/LC3-I比值降低(P<0.05)。与模型组相比,ICSⅡ高剂量组大鼠逃避潜伏期缩短(P<0.05),穿越原平台象限次数增加(P<0.05);Aβ1-42的蛋白含量明显降低(P<0.05),LC3-Ⅱ/LC3-Ⅰ比值及Beclin 1蛋白表达显著增加(P<0.05)。结论自噬途径参与了STZ诱导的大鼠学习记忆减退;ICSⅡ具有抗侧脑室注射STZ诱导的认知功能损伤作用,其机制可能与诱导细胞自噬有关。 Objective To explore the effect and mechanism of icariin Ⅱ (ICS Ⅱ) on learning and memory impairment induced by streptozotocin (STZ) in rats. Methods Male Sprague-Dawley rats were randomly divided into sham operation group, model group, low and high ICS Ⅱ group (all n = 10). Rats in model group and ICSⅡgroup were injected with STZ 5μL (1.5 mg · kg -1) into simulated bilateral Alzheimer’s disease on day 1 and day 3, and sham operation group were injected with equal volume of citrate buffer . After the second operation, ICSⅡ and 10 mg · kg -1 were given intragastrically to ICS Ⅱ low and high dose groups, respectively. The rats in sham operation group and model group were given equal volume of double distilled water for 21 days. On the 16th day after the administration, the 6-day Morris water maze test was used to detect the behavioral function in rats. After the water maze test, the protein expression of autophagy gene Beclin 1, microtubule-associated protein 1 light chain 3 (LC3) Ⅰ and LC3 Ⅱ in rat hippocampus and the expression of β-amyloid protein (Aβ1-42 ) Content. Results In the water maze test, the mean escape latency of the model group was significantly longer than that of the sham operation group (P <0.05); the content of Aβ1-42 in the hippocampus was significantly increased (P <0.05); Beclin 1 (P <0.05), and the ratio of LC3-Ⅱ / LC3-I decreased (P <0.05). Compared with the model group, the escape latency of ICSⅡhigh dose group was shorter (P <0.05) and the number of crossing the original platform quadrant increased (P <0.05); the protein content of Aβ1-42 decreased significantly (P <0.05) / LC3-Ⅰ ratio and Beclin 1 protein expression increased significantly (P <0.05). Conclusion The autophagy pathway is involved in STZ-induced learning and memory decline. ICSⅡ has an anti-STZ-induced cognitive impairment effect, which may be related to the induction of autophagy.