基础医学与临床
基礎醫學與臨床
기출의학여림상
BASIC MEDICAL SCIENCES AND CLINICS
2010年
1期
54-58
,共5页
魏子峰%王永生%王茜%马立人%张作凤%高俊玲%张宇新
魏子峰%王永生%王茜%馬立人%張作鳳%高俊玲%張宇新
위자봉%왕영생%왕천%마립인%장작봉%고준령%장우신
帕金森病%半胱氨酸蛋白酶-3%磷酸化P38 MAPK%酪氨酸羟化酶%1-甲基-4-苯基-1,2,3,6-四氢吡啶
帕金森病%半胱氨痠蛋白酶-3%燐痠化P38 MAPK%酪氨痠羥化酶%1-甲基-4-苯基-1,2,3,6-四氫吡啶
파금삼병%반광안산단백매-3%린산화P38 MAPK%락안산간화매%1-갑기-4-분기-1,2,3,6-사경필정
Parkinson's disease%caspase-3%p-P38 MAPK%TH%MPTP
目的 研究磷酸化P38 MAPK在1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)所致帕金森病(PD)模型小鼠中对黑质半胱氨酸蛋白酶-3(caspase-3)的调控作用.方法 将小鼠随机分为MPTP模型组,腹腔注射MPTP(30 mg/kg,生理盐水溶);抑制剂组,在注射MPTP前1 h腹腔注射SB203580(10 mg/kg,溶于5 mg/mL DMSO).均1次/d,连续5 d;对照组,注射与模型组和抑制剂组等量生理盐水和DMSO.观察行为学、免疫组织化学和免疫蛋白印迹法观察黑质酪氨酸羟化酶(TH)、caspase-3和磷酸化P38 MAPK(p-P38 MAPK)的表达.结果 与对照组相比,模型小鼠出现典型的PD症状,TH阳性神经元和蛋白水平分别下降约60%和65%(P<0.01),p-P38 MAPK、caspase-3阳性细胞及蛋白水平显著增加(P<0.01);经P38 MAPK抑制剂SB203580处理后,上述变化均显著减轻(P<0.01).结论 磷酸化P38 MAPK在MPTP诱导的PD小鼠黑质caspase-3表达中可能有重要调控作用,SB203580对PD小鼠具有一定的神经保护作用.
目的 研究燐痠化P38 MAPK在1-甲基-4-苯基-1,2,3,6四氫吡啶(MPTP)所緻帕金森病(PD)模型小鼠中對黑質半胱氨痠蛋白酶-3(caspase-3)的調控作用.方法 將小鼠隨機分為MPTP模型組,腹腔註射MPTP(30 mg/kg,生理鹽水溶);抑製劑組,在註射MPTP前1 h腹腔註射SB203580(10 mg/kg,溶于5 mg/mL DMSO).均1次/d,連續5 d;對照組,註射與模型組和抑製劑組等量生理鹽水和DMSO.觀察行為學、免疫組織化學和免疫蛋白印跡法觀察黑質酪氨痠羥化酶(TH)、caspase-3和燐痠化P38 MAPK(p-P38 MAPK)的錶達.結果 與對照組相比,模型小鼠齣現典型的PD癥狀,TH暘性神經元和蛋白水平分彆下降約60%和65%(P<0.01),p-P38 MAPK、caspase-3暘性細胞及蛋白水平顯著增加(P<0.01);經P38 MAPK抑製劑SB203580處理後,上述變化均顯著減輕(P<0.01).結論 燐痠化P38 MAPK在MPTP誘導的PD小鼠黑質caspase-3錶達中可能有重要調控作用,SB203580對PD小鼠具有一定的神經保護作用.
목적 연구린산화P38 MAPK재1-갑기-4-분기-1,2,3,6사경필정(MPTP)소치파금삼병(PD)모형소서중대흑질반광안산단백매-3(caspase-3)적조공작용.방법 장소서수궤분위MPTP모형조,복강주사MPTP(30 mg/kg,생리염수용);억제제조,재주사MPTP전1 h복강주사SB203580(10 mg/kg,용우5 mg/mL DMSO).균1차/d,련속5 d;대조조,주사여모형조화억제제조등량생리염수화DMSO.관찰행위학、면역조직화학화면역단백인적법관찰흑질락안산간화매(TH)、caspase-3화린산화P38 MAPK(p-P38 MAPK)적표체.결과 여대조조상비,모형소서출현전형적PD증상,TH양성신경원화단백수평분별하강약60%화65%(P<0.01),p-P38 MAPK、caspase-3양성세포급단백수평현저증가(P<0.01);경P38 MAPK억제제SB203580처리후,상술변화균현저감경(P<0.01).결론 린산화P38 MAPK재MPTP유도적PD소서흑질caspase-3표체중가능유중요조공작용,SB203580대PD소서구유일정적신경보호작용.
Objective To investegate the effect of phosphorylated-P38 MAPK(mitogen-activated protein kinase) on the expression of caspase-3 in the substania nigra (SN) of MPTP-induced mouse model of(PD). Methods Mice were randomly divided into MPTP model group, which were treated with MPTP and inhibitor group. Once a day for 5 days; control group was treated with saline and DMSO as much as the model group received per day for 5 days. The behavioral were observed, immunohistochemistry and Western blot for TH, caspase-3 and phosphorylation of P38 MAPK were used to observe the change of positive cell number and the expression level in the SN of midbrain. Results Compared with the mice in control group, the model group showed typical symtoms of PD with decreased numbers of TH-positive neurons and the protein level of TH in SN of the midbrain by about 60% and 65% respec-tively(P<0.01) , the numbers of caspase-3 and phosphorylation of P38 MAPK immunoreactive cells and their protein level in the SN of the midbrain increased markedly (P<0.01). After giving SB203580, the above changes were reduced obviously (P <0. 01). Conclusion In the mouse model of subacute Parkinson's disease induced by MPTP, phosphorylated-P38 MAPK regulated caspase-3 in the SN of midbrain, the specific P38 MAPK inhibitor SB203580 is neurologically oprotective to the mouse model.
