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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 possible mechanism of insulin lowering amyloid beta peptide (Aβ) in cerebral cortex neurons of diabetic rats. Methods Fifteen male Sprague-Dawley rats were randomly divided into normal control group, diabetic group and diabetic + insulin group, with 5 rats in each group. Diabetic rats were induced by streptozotocin (STZ). The activity of glycogen synthase kinase 3 (GSK3) in cerebral cortex neurons was detected by 32P radioligand binding assay. The activity of GSK3 was detected by enzyme linked immunosorbent assay (ELISA) Aβ production and Western blot detection of amyloid precursor protein (APP) expression. Results Compared with the control group [GSK3 (1.04 ± 0.11), Aβ40 (40.92 ± 5.34) pg / μl, Aβ42 (29.64 ± 3.19) pg / μl, APP (1.05 ± 0.08)], GSK3 activity in diabetic group (2.02 ± 0.12 ) And Aβ (67.53 ± 11.69 pg / μl, Aβ42 (45.02 ± 4.10) pg / μl] and APP (1.52 ± 0.16) (P <0.01), and significantly decreased the activity of GSK3 (1.21 ± 0.17, P <0.01) and Aβ40 (42.96 ± 6.03) pg / μl in the cerebral cortex of diabetic rats However, APP expression (1.39 ± 0.13) did not change significantly. Conclusions Aβ production is increased in cortical neurons of diabetic rats. GSK3 plays an important role in this process. Insulin inhibits the production of Aβ by inhibiting GSK3.