中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2014年
2期
161-167
,共7页
刘志华%汪惠丽%吴圣%刘阳%陈向涛
劉誌華%汪惠麗%吳聖%劉暘%陳嚮濤
류지화%왕혜려%오골%류양%진향도
双酚 A%树突棘%Wnt 信号通路%突触形成
雙酚 A%樹突棘%Wnt 信號通路%突觸形成
쌍분 A%수돌극%Wnt 신호통로%돌촉형성
bisphenol A%dendritic spine%Wnt signaling%synapse formation
目的:探讨发育关键期双酚 A(BPA)暴露对海马齿状回(DG)区突触形成和树突棘的影响及其机制。方法出生7 d 的 SD 大鼠,腹腔注射 BPA 50,250和500μg·kg -1·d -1,连续7 d。Golgi-Cox 染色分析海马 DG 区树突棘密度和树突棘头形态大小,Western blotting 检测β联蛋白,Wnt7a 及 Wnt5a 蛋白表达。结果BPA 50,250和500μg·kg -1组海马 DG 区树突棘密度依次为9.67±0.17,8.97±0.13,(8.71±0.15)/10μm,相对于正常对照组的(10.21±0.17)/10μm,BPA 50,250和500μg·kg -1·d -1组树突棘密度显著下降(P<0.05)。正常对照组树突棘头为(0.67±0.03)μm2,BPA 50,250和500μg·kg -1组树突棘头依次为0.53±0.03,0.51±0.03和(0.50±0.03)μm2,显著低于正常对照组(P <0.05)。BPA 50,250和500μg·kg -1·d -1组磷酸化的β联蛋白占总体β联蛋白的百分比分别提高了18.28%,32.22%和57.01%,而 Wnt7a 表达显著降低(P<0.05),Wnt5a 表达显著提高(P<0.05)。结论在 BPA 所引起的突触形成和树突棘的损伤中,Wnt 信号通路可能起关键作用。
目的:探討髮育關鍵期雙酚 A(BPA)暴露對海馬齒狀迴(DG)區突觸形成和樹突棘的影響及其機製。方法齣生7 d 的 SD 大鼠,腹腔註射 BPA 50,250和500μg·kg -1·d -1,連續7 d。Golgi-Cox 染色分析海馬 DG 區樹突棘密度和樹突棘頭形態大小,Western blotting 檢測β聯蛋白,Wnt7a 及 Wnt5a 蛋白錶達。結果BPA 50,250和500μg·kg -1組海馬 DG 區樹突棘密度依次為9.67±0.17,8.97±0.13,(8.71±0.15)/10μm,相對于正常對照組的(10.21±0.17)/10μm,BPA 50,250和500μg·kg -1·d -1組樹突棘密度顯著下降(P<0.05)。正常對照組樹突棘頭為(0.67±0.03)μm2,BPA 50,250和500μg·kg -1組樹突棘頭依次為0.53±0.03,0.51±0.03和(0.50±0.03)μm2,顯著低于正常對照組(P <0.05)。BPA 50,250和500μg·kg -1·d -1組燐痠化的β聯蛋白佔總體β聯蛋白的百分比分彆提高瞭18.28%,32.22%和57.01%,而 Wnt7a 錶達顯著降低(P<0.05),Wnt5a 錶達顯著提高(P<0.05)。結論在 BPA 所引起的突觸形成和樹突棘的損傷中,Wnt 信號通路可能起關鍵作用。
목적:탐토발육관건기쌍분 A(BPA)폭로대해마치상회(DG)구돌촉형성화수돌극적영향급기궤제。방법출생7 d 적 SD 대서,복강주사 BPA 50,250화500μg·kg -1·d -1,련속7 d。Golgi-Cox 염색분석해마 DG 구수돌극밀도화수돌극두형태대소,Western blotting 검측β련단백,Wnt7a 급 Wnt5a 단백표체。결과BPA 50,250화500μg·kg -1조해마 DG 구수돌극밀도의차위9.67±0.17,8.97±0.13,(8.71±0.15)/10μm,상대우정상대조조적(10.21±0.17)/10μm,BPA 50,250화500μg·kg -1·d -1조수돌극밀도현저하강(P<0.05)。정상대조조수돌극두위(0.67±0.03)μm2,BPA 50,250화500μg·kg -1조수돌극두의차위0.53±0.03,0.51±0.03화(0.50±0.03)μm2,현저저우정상대조조(P <0.05)。BPA 50,250화500μg·kg -1·d -1조린산화적β련단백점총체β련단백적백분비분별제고료18.28%,32.22%화57.01%,이 Wnt7a 표체현저강저(P<0.05),Wnt5a 표체현저제고(P<0.05)。결론재 BPA 소인기적돌촉형성화수돌극적손상중,Wnt 신호통로가능기관건작용。
OBJECTIVE To investigate the effects and its underlying mechanis m of bisphenol-A (BPA)exposure on spine and synapse formation in detate gyrus (DG)area of hippoca mpus during criti-cal develop mental period.METHODS Sprague-Dawley(SD)rats were injected intraperitoneally with BPA (50,250 and 500 μg·kg -1·d -1 )fro m postnatal day 7 (PND7)to PND14.Dendritic spine morphol-ogy in DG area was exa mined using Golgi-Cox staining method and determined with I mage J software. Western blotting method was e mployed to test the Wnt related proteins.RESULTS The spine density and the average spine head size in BPA exposed groups significantly decreased in a dose-dependent manner when co mpared to control group(P<0.05).Meanwhile,Wnt related proteins were affected dur-ing BPA exposure.Specifically,the percentage of phosphorylated β-catenin increased following BPA ex-posure (P<0.05),whereas Wnt7a expression level was significantly decreased and Wnt5a expression level increased (P<0.05).CONCLUSION Wnt signaling pathway plays an i mportant role in BPA-in-duced i mpairments in spine and synapse formation.