ApoE基因缺陷鼠免疫、血液稳态和抗氧化功能改变

目的:探讨载脂蛋白E(apoproteinE,ApoE)功能障碍对脂质代谢、血液稳态、脾T淋巴细胞亚群及自由基代谢的影响.方法:以ApoE基因缺陷(ApoE0)鼠为实验模型,以相同遗传背景的C57BL/6J鼠为对照,对比血浆中有关指标的不同.结果:与对照组比较,ApoE0鼠的总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)和低密度脂蛋白胆固醇(10w density lipoprotein cholesterol,LDL-C)水平均高于正常对照鼠(P＜0.05),而ApoE0鼠的高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)仅为正常对照鼠的1/5(P＜0.01);ApoE0鼠的血浆组织纤溶酶原激活物活性(tissue plasminogen activator activity,tPAa)增加18.3%(P＞0.05),纤溶酶原激活抑制剂活性(plasminogen activatorinhibitor activity,PAIa)下降19.6%(P＜0.05),使tPAa/PAIa升高55%(P＜0.01);ApoE0鼠的凝血酶原活性、凝血酶活性和纤溶酶活性分别升高54.2%(P＜0.01)、135%(P＜0.01)和37.6%(P＜0.01),而纤溶酶原活性降低24.3%(P＜0.01);ApoE0鼠CD4+和CD8+分别降低17.2%(P＜0.05)和58.9%(P＜0.01),CD4+/CD8+升高146%(P＜0.01);ApoE0鼠血浆超氧化物岐化酶(superoxide dismutase,SOD)活性降低17.5%(P＜0.01),MDA水平增加29.8%(P＜0.01),肝脏SOD活性有下降趋势(P ＞0.05),而丙二醛(malonadehyde,MDA)含量升高99%(P＜0.01);两种鼠血管的SOD活性和MDA水平差异无显著性(P＞0.05).结论:ApoE基因缺陷鼠造成脂质代谢紊乱,还使凝血和纤溶功能亢进、淋巴细胞亚群比例失调及血浆氧化-抗氧化平衡破坏等异常.利用这一模型进行的有关研究应同时考虑由于ApoE功能障碍引起的这些变化.

Changes of immune, haemostasis and anti-oxidation functions in ApoE gene deficiency mice

Objective: To study influence of ApoE dysfunction on haemostasis, T cell subpopulations and metabolism of lipids and free radicals. Methods: ApoE gene knockout (ApoE0) mice were used as the subjects and the homogeneous mice of C57BL/6J as the control. Results: In comparison with control, TC, TG and LDL C levels were higher in ApoE0 mice ( P <0.05), and their HDL C level was only 20% of the control ( P <0.01); the activity detected was 18.3% higher ( P <0.05) for tPA and 19.6% lower ( P <0.01) for PAI, and the ratio of tPA/PAI was 55% higher ( P <0.01) in ApoE0 mice; the activity of thrombinogen, thrombin and plasmin increased by 54.2% ( P <0.01), 135% ( P <0.01) and 37.6% ( P <0.01) respectively, and plasminogen decreased by 24.3 ( P <0.01) in ApoE0 mice; T cell subpopulation of CD4 + and CD8 + in ApoE0 mice decreased by 17.2% ( P < 0.01) and 58.9% ( P <0.01) respectively, and the ratio of CD4 +/CD8 + increased by 146% ( P < 0.01); SOD of ApoE0 mice was 17.5% lower ( P <0.01) and MDA was 29.8 ( P <0.01) higher in plasma, while SOD decreased insignificantly ( P >0.05) and MDA increased by 99% ( P <0.01) inliver; there were no differences in SOD activity and MDA level between two groups ( P >0.05) Conclusion: ApoE dysfunction causes disturbance of lipid metabolism, hyperfunction of coagulation and fibrinolysis, change of proportion of T cell subpopulation and disorder of oxidation and antioxidation balance.