半枝莲总黄酮对ApoE基因缺陷小鼠动脉粥样硬化及磷脂转运蛋白表达的影响  

Effects of the total flavonoids of scutellaria barbataon on atherosclerosis and expression of PLTP in Apo E gene deficiency mice

作　　者：祝娉婷[1] 孙云[1] 刘兆国[2] 刘玉萍[2] 卜平[1] 

机构地区：[1]扬州大学医学院,江苏扬州225001 [2]南京中医药大学药学院,江苏南京210023

出　　处：《中国药理学通报》2015年第6期833-838,共6页Chinese Pharmacological Bulletin

基　　金：教育部博士点基金资助项目(No 20123250120003);江苏省自然科学基金资助项目(No BK20140493);江苏省高校面上项目(No 13KJB360015);江苏省中医药局科技项目(No LZ13249)

摘　　要：目的探讨半枝莲总黄酮(TFSB)对高脂饲养Apo E基因缺陷(Apo E-/-)小鼠在动脉粥样硬化(AS)病变形成早期抑制AS的作用及其分子机制。方法 11周龄♂Apo E-/-小鼠40只,随机分为模型组、TFSB低、中、高剂量组、辛伐他汀组,每组8只。取C57BL/6J小鼠8只作为正常对照组。均给予高脂饲养4周后给药,8周后全部处死,HE染色观察主动脉形态学变化,血液流变仪测血浆黏度、全血黏度(低切、高切),温氏法测红细胞比容。全自动生化分析仪检测血清TG、TC、HDL-C、LDL-C表达水平,ELISA法检测血清磷脂转运蛋白(PLTP)及维生素E(VE)的表达水平。Western blot法检测各组小鼠肝脏PLTP蛋白表达水平及法尼酯衍生物X受体(FXR)表达水平。结果模型组造模成功;TFSB各剂量组对模型小鼠主动脉AS形态学有改善作用,可明显降低AS模型小鼠血清TG、TC、LDL-C水平,升高HDL-C水平,与模型组比较,差异均具有显著性(P<0.05或P<0.01);TFSB各剂量组可明显降低AS模型鼠的红细胞比容、血浆黏度及全血黏度(低切、高切),且与模型组相比,差异均有显著性(P<0.01);TFSB各剂量组血清PLTP表达水平较模型组明显减少,差异均有显著性(P<0.01),且PLTP与VE水平呈负相关(r=-0.675,P<0.01);与模型组相比,TFSB中、高剂量组能够明显抑制肝脏PLTP及FXR蛋白表达水平(P<0.01)。结论 TFSB可能通过调节Apo E-/-小鼠FXR水平,从而调节PLTP水平、升高VE水平、调节血脂、改善血液流变学及减少小鼠的AS损伤,进而发挥抗AS的作用。Aim To observe the effects of the total fla-vonoids of scutellaria barbataon （ TFSB ） on high-fat feeding ApoE gene deficiency mice in early atheroscle-rosis （ AS ） and its underlying mechanisms. Methods 40 ApoE^-/ -male mice were divided into five groups：model group, SIM group and L-TFSB, M-TFSB, H-TFSB group, 5 C57BL/6J mice were selected as nor-mal control group. All mice in experimental group were fed with high-lipid diet for 4 weeks and all mice were killed after 8 weeks. H＆E staining was used to observe morphology of aorta. Blood rheometer was used to ex-amine plasm viscosity and whole blood viscosity. Fully automatic biochemical analyser was used to detect the serum levels of TG, TC, LDL-C and HDL-C. The ex-pression levels of PLTP and VE in serum were meas-ured by ELISA. The expression levels of PLTP and FXR in liver were examined by Western blot. Results The model was established successfully. TFSB groups could improve the aorta AS morphology of model mice and significantly reduce the serum levels of TG, TC and LDL-C, while increase the level of HDL-C （ P〈0. 05 or P〈0. 01 ） . TFSB groups could decrease the hematocrit value, plasma viscosity and whole blood vis-cosity of AS model mice significantly and had statistical significance when compared with model group （ P 〈0. 01 ） . The expression levels of PLTP of serum were reduced significantly when compared with model group （ P 〈0. 01 ） . We also found that the expression of PLTP was in negative correlation with VE （ r = -0. 675,P〈0. 01）. M-TFSB and H-TFSB group could decrease the expressions of PLTP and FXR of liver when compared with model group （ P 〈0. 01 ） . Con-clusion TFSB may exert its anti-AS effect partly through inhibiting the levels of FXR and PLTP of ApoE^-/ -mice, increasing the level of VE, regulating blood lipids, improving blood rheology and reducing the damage of AS in mice.

关 键 词：AS TFSB APO E^-/-小鼠 血脂 PLTP FXR 

分 类 号：R-332[医药卫生] R284.1