【摘要】 目的　探讨用 β淀粉样肽前体蛋白 (APP)中的某些肽段免疫小鼠可否减轻小鼠脑内 β淀粉样肽 (Aβ)及其前体蛋白 (APP)的表达。方法　分别用 APP中的 31 9- 335肽段 (APP1 7肽 )、597- 62 4肽段 (APP2 8肽即 Aβ1 - 2 8)免疫小鼠 ,APP1 7肽、Aβ1 - 2 8由我室合成并纯化。第 3次免疫后 ,诱发小鼠糖尿病模型。小鼠分 4组 :即用 APP1 7肽免疫的正常小鼠 (1 7PC) ;用 APP1 7肽免疫后诱发糖尿病的小鼠 (1 7PDM) ;用 Aβ1 - 2 8免疫的正常小鼠 (2 8PC) ;用 Aβ1 - 2 8免疫后诱发糖尿病的小鼠 (2 8PDM)。第 5次免疫后 ,对各组小鼠脑切片进行 Aβ类抗体的免疫组织化学染色。结果　 1 7PC组小鼠海马内表达 Aβ1 - 4 2、 Aβ1 - 1 6及 APP C端抗体的阳性染色神经元数目多 ,而 1 7PDM组小鼠海马内上述各种抗体的阳性染色数目比 1 7PC组明显减少 (P<0 .0 1 ) ;2 8PC组小鼠海马内表达 Aβ1 - 4 2、Aβ1 - 1 6及 APP N端抗体的阳性染色神经元数目多 ,而 2 8PDM组小鼠海马内上述各种抗体阳性染色的数目比 2 8PC组明显减少 (P<0 .0 1 )。结论　糖尿病小鼠血 -脑屏障破坏 ,抗体进入脑组织 ,与β淀粉样肽或其前体蛋白结合而使之易被清除。更多还原

【Abstract】 Objective To investigate whether immunization with the peptide fragments of β amyloid precursor protein (APP) attenuates the expression of β amyloid and APP in the brains of diabetic mice Methods Mice were immunized with the 319 335 peptide fragment of APP (APP17mer peptide) and 597 624 peptide fragments of APP (APP28mer peptide i e Aβ1 28) APP17mer peptide and Aβ1 28 were synthesized and purified by HPLC in our laboratory After the third immunization, mice diabetic models were produced with streptozotocin (STZ) The mice were divided into four groups: normal mice immunized with APP17mer peptide (17PC); diabetic mice immunized with APP17mer peptide (17PDM); normal mice immunized with Aβ1 28 (28PC); diabetic mice immunized with Aβ1 28 (28PDM) Cryostat sections of mice brain were prepared after the fifth immunization Immunohistochemistry were studied for Aβ1 16、Aβ42、APP C teminal、APP N terminal( APP 52 80 amino acid sequence) antibodies Results There are neurons stained positively by Aβ1 16、Aβ42、APP C terminal antibodies in the brain of 17PC group In contrast to 17PC group the number of positively stained hippocampal cells in 17PDM group were markedly reduced ( P <0 01) The number of neurons positive for Aβ1 16、Aβ42 and APP N terminal in the brain of 28PC group was numerous, while in the brain of 28PDM group there were little positively stained neurons( P <0 01) Conclusions The blood brain barrier of diabetic mice is damaged The antibodies which entered the brain combined with β amyloid or APP and so attenuated the expression of β amyloid or APP更多还原