APP5肽类似物165对老年性痴呆模型大鼠行为学及PSD95和Shank 1表达的影响

目的观察5肽类似物165对老年性痴呆(Alzhei mer disease,AD)模型大鼠学习记忆能力及突触后致密区蛋白95(postsynaptic density95,PSD95)和骨架蛋白Shank1表达的影响。方法将45只大鼠随机分为正常对照组、模型组和5肽类似物165治疗组,模型组和治疗组大鼠按体重3mg/kg行双侧侧脑室链脲佐菌素(streptozotocin,STZ)注射,第3天重复注射建立AD模型,对照组以人工脑脊液代替STZ。术后21d治疗组按体重0.34mg/(kg.d)给予APP5肽类似物165灌胃干预,其余两组以蒸馏水代替。3周后应用Morris水迷宫、免疫组织化学和Western blotting方法检测大鼠的学习记忆能力及PSD95和Shank1的表达。结果5肽类似物165治疗组大鼠的平均游泳时间较模型组明显缩短(P<0.01),且海马PSD95和Shank1阳性神经细胞数及PSD95和Shank1蛋白表达较模型组明显增加(P<0.05)。结论5肽类似物165可显著提高大鼠学习记忆能力,增加大鼠海马PSD95和Shank1表达,表明其对突触功能和可塑性具改善作用。

Photoprotective effect of the N-terminal 5-mer peptide analog P165 of amyloid precursor protein in human dermal fibroblasts

Background We showed in our previous study that the N-terminal 17-mer peptide of amyloid precursor protein （APP17-mer peptide）,an active peptide segment with trophic and antioxidative effects,protects skin fibroblasts against ultraviolet （UV） damage and downregulates matrix metalloproteinase 1 （MMP-1） expression.The aim of the current study was to explore the protective effects of P165,the N-terminal 5-mer peptide analog of amyloid precursor protein that is resistant to enzymolysis,on UVA-induced damage in human dermal fibroblasts （HDFs）.Methods HDFs were cultured in Dulbecco＆#39;s modified Eagle＆#39;s medium without and with P165 （concentrations were 1,10,and 100 μJmol/L）.Then,15 J/cm2 UVA irradiation was used to obtain the UV-irradiated model.Cell proliferation was analyzed using MTT kit.The collagen type Ⅰ and MMP-1 contents in cell lysate were determined by enzyme-linked immunosorbent assay （ELISA）.Fluorometric assays were performed to detect the formation of intracellular reactive oxygen species （ROS） in the cells.Results P165 significantly protected the HDFs against UVA-induced cytotoxicity.Compared with the UVA-irradiated control,1,10,and 100 μmol/L P165 elevated cell proliferation by 14.98% （P〈0.05）,17.52% （P〈0.01） and 28.34% （P〈0.001）,respectively.Simultaneously,10 and 100 μmol/L P165 increased collagen type Ⅰ content （both P〈0.05）.Moreover,P165 treatment （all concentrations） also markedly suppressed the UVA-induced MMP-1 expression （all P〈0.001）.P165 at 1,10,and 100 μmol/L also reduced UVA-induced ROS generation by 11.27%,13.69% （both P〈0.05）,and 25.48% （P〈0.001）,respectively.Conclusions P165 could protect the HDFs against UVA-induced photodamage,including cytotoxicity,and MMP-1 generation.Furthermore,it also increased the collagen type Ⅰ content in the cells.The inhibitory effect on intracellular ROS generation might be involved in these photoprotective effects.Thus,P165 may be a useful candidate in the prevention and treatment of skin photoaging.

β淀粉样肽前体蛋白N端328-332类似物165对谷氨酸引起神经毒作用的影响

目的通过观察β淀粉样肽前体蛋白N端328-332(APP5肽)类似物165对谷氨酸引起神经毒性作用的影响,进一步证实APP5肽类似物165的神经营养作用。方法以人神经母细胞瘤株SY5Y为细胞模型,分为正常对照组、谷氨酸500μmol/L损伤组和谷氨酸500μmol/L加APP5肽及类似物165各40μmol/L保护组。以MTT代谢率、LDH漏出率、细胞轴突长度和胞体面积作为观察指标。结果与正常对照组相比,谷氨酸损伤组MTT代谢率降低,LDH漏出率升高,轴突长度和胞体面积均缩小;而加入APP5肽及类似物165保护后,可使上述指标得以改善。结论APP5肽及类似物165具有神经营养作用,可减轻谷氨酸引起的神经元损伤。