胰岛素降低糖尿病大鼠大脑皮质β-淀粉样蛋白含量的可能机制  

The possible mechanism of insulin reducing amyloid beta peptide in the brain cortex of diabetic rats

作　　者：曲忠森[1] 赵永波[1] 刘文文[1] 王建枝[2] 

机构地区：[1]上海交通大学附属第一人民医院神经科,200080 [2]华中科技大学同济医学院病理生理系

出　　处：《中华神经科杂志》2006年第6期392-395,共4页Chinese Journal of Neurology

摘　　要：目的探讨胰岛素降低糖尿病大鼠大脑皮质神经元中β淀粉样蛋白(amyloidbeta peptide,Aβ)的可能机制。方法雄性SD大鼠15只,随机分为正常对照组、糖尿病组、糖尿病+胰岛素组,每组5只。用链脲佐菌素建立糖尿病大鼠模型,用32P放射性配体结合实验检测3组大鼠大脑皮质神经元中糖原合酶激酶3(GSK3)的活性,酶联免疫吸附(ELISA)法检测Aβ的产量及Western blot检测淀粉样前体蛋白(APP)的表达。结果与对照组[GSK3(1.04±0.11),Aβ40(40.92±5.34)pg/μl,Aβ42(29.64±3.19)pg/μl,APP(1.05±0.08)]相比,糖尿病组GSK3活性(2.02±0.12)和Aβ生成[Aβ40(67.53±11.69)pg/μl,Aβ42(45.02±4.10)pg/μl]明显增加(P<0.01),APP(1.52±0.16)表达增加(P<0.05);应用胰岛素后能明显降低GSK3活性(1.21±0.17,P<0.01)和糖尿病大鼠大脑皮质Aβ[Aβ40(42.96±6.03)pg/μl,P<0.05;Aβ42(31.09±3.94)pg/μl,P<0.01]水平,但APP的表达(1.39±0.13)无明显改变。结论糖尿病大鼠皮质神经元Aβ生成增加,GSK3在这一过程中起着重要作用;胰岛素通过抑制GSK3可降低Aβ的生成。Objective To investigate the reduction of amyloid beta peptide （Aβ） production induced by insulin in the cortex of diabetic rat. Methods 15 male SD rats were randomly divided into control group, diabetes group, and diabetes plus insulin group. The diabetic rats were induced by streptozotocin. The activity of glycogen synthase kinase-3 （GSK-3） was measured by ^32P liquid scintillography for incorporated radioactivity in control group, DM group, DM ＋ insulin group, the production of Aβ was determined by sandwich ELISA in each group, and the expression of APP was determined by Western-blot. Results In control group, the activity of GSK-3 （ 1.04 ± 0. 11 ） , the production of Aβ（ Aβ40（ 40. 92 ± 5. 34 ） pg/μl, Aβ42 （ 29. 64 ± 3.19 ） pg/μl ） and the levels of full-length APP （ 1.05 ± 0.08） was low, but in DM group, the activity of GSK-3 （2.02 ±0. 12） and the production of Aβ（Aβ40 （67. 53 ± 11.69 ） pg/μl, Aβ42 （ 45. 02 ± 4. 10 ） pg/μl ） increased （ P 〈 0. 01 ）, accompanied by the elevated levels of full-length APP （ 1.52 ± 0. 16, P 〈 0. 05 ）. The activity of GSK-3 （ 1.21 ± 0. 17 ） was decreased （ P 〈 0. 01 ）, the production of Aβ （ Aβ40 （42. 96 ± 6. 03 ） pg/μl, P 〈 0. 05 ; Aβ42 （ 31.09 ± 3.94 ） pg/μl,P〈0. 01 ） was also decreased after insulin treatment, and the elevated levels of full-length APP （ 1.39 ± 0. 13） was not changed compared with that of DM group. Conclusions The production of Aβ increases in diabetes, GSK-3 might play an important role in this process, and insulin decreases Aβ production by inhibiting GSK-3.

关 键 词：糖尿病 实验性 糖原合成酶激酶3 淀粉样Β蛋白前体 淀粉样Β蛋白 胰岛素 

分 类 号：R587.1[医药卫生—内分泌] R749.16[医药卫生—内科学]