CAJ | 학술논문

目的:观察小檗碱对2型糖尿病海马CA3区损伤的保护作用及其该过程中过氧化物酶体增殖物激活受体(PPARs)α/δ/γ和正性转录延伸因子b(P-TEflb)的作用.方法:腹腔注射35 mg/kg链脲菌素加高糖高脂饲料喂养16周建立2型糖尿病大鼠模型,随后16周每天分别给予低中高剂量小檗碱75、150、300 mg/kg、非诺贝特100 mg/kg和罗格列酮4 mg/kg,处死大鼠后用HE染色检杳海马CA3区和免疫组化技术检测PPARα、δ、γ和Cdk9、cyclin T1的表达.结果:糖尿病大鼠海马CA3区的锥体细胞形状和排列变得不规则、数量减少,中高剂量小檗碱和罗格列酮能恢复受损伤的锥体细胞接近正常大鼠的水平.在海马CA3区几乎检测不到PPARγ蛋白的表达,中高剂量小檗碱和非诺贝特明显增加糖尿病大鼠中减少了的PPARα和PPARδ表达(P<0.01);中高剂量小檗碱和罗格列酮能明显使降低了的Cdk9和cyclin T1表达恢复至正常水平(P<0.01).结论:小檗碱调控海马CA3区PPARα/δ和正性转录延伸因子b(Cdk9和cyclin T1)蛋白的表达可能是其改善海马锥体细胞损伤的机制之一.
목적:관찰소벽감대2형당뇨병해마CA3구손상적보호작용급기해과정중과양화물매체증식물격활수체(PPARs)α/δ/γ화정성전록연신인자b(P-TEflb)적작용.방법:복강주사35 mg/kg련뇨균소가고당고지사료위양16주건립2형당뇨병대서모형,수후16주매천분별급여저중고제량소벽감75、150、300 mg/kg、비낙패특100 mg/kg화라격렬동4 mg/kg,처사대서후용HE염색검묘해마CA3구화면역조화기술검측PPARα、δ、γ화Cdk9、cyclin T1적표체.결과:당뇨병대서해마CA3구적추체세포형상화배렬변득불규칙、수량감소,중고제량소벽감화라격렬동능회복수손상적추체세포접근정상대서적수평.재해마CA3구궤호검측불도PPARγ단백적표체,중고제량소벽감화비낙패특명현증가당뇨병대서중감소료적PPARα화PPARδ표체(P<0.01);중고제량소벽감화라격렬동능명현사강저료적Cdk9화cyclin T1표체회복지정상수평(P<0.01).결론:소벽감조공해마CA3구PPARα/δ화정성전록연신인자b(Cdk9화cyclin T1)단백적표체가능시기개선해마추체세포손상적궤제지일.
AIM: To investigate the protective effect of berberine on the diabetic CA3 region of hippocampus injury and the role of peroxisome proliferator-activated receptors (PPARs) α/δ/γ and positive transcription elongation factor b (P-TEFb) in this process. METHODS: Diabetic rats were induced by an injection of 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet for 16 weeks. At the end of week 16, the rats were divided into 7 groups: the control group rats and the diabetic model group rats were treated with no drugs, diabetic rats of the other five groups were given low-dose, middle-dose, high-dose berbefine (75, 150,300 mg/kg), fenofibrate (100 mg/kg) and rosiglitazone (4 mg/kg) every day, respectively. The CA3 region of hippocampus morphology was observed with HE staining, and PPARα/δ/γ and P-TEFb (Cdk9 and cyclin T1) expression were detected by immunohistochemistry analysis. RESULTS: Pyramidal cells were lost in the CA3 region of diabetic rat hippocampus with the shape and arrangement of cells less organized, 16-week treatment with middle-dose, high-dose berberine restored the damaged pyramidal cells to near control. PPARγ protein expression was barely detectable in the CA3 region of hippocampus, middle-dose, high-dose berberine and fenofibrate strikingly increased both PPARα and PPARδ expression in diabetic (P < 0.01); middle-dose, high-dose berberine and rosiglitazone markedly took the decreased Cdk9 and cyclin T1 expression back to control level (P < 0.01). CONCLUSION: Berberine modulates PPARα/δ and P-TEFb (Cdk9 and cyclin T1) protein expression in the CA3 region of diabetic rat hippocampus which may contribute to ameliorate pyramidal cells damage.