建立基因敲除小鼠颈动脉粥样硬化模型(ppt)课件.ppt

1、Lipoprotein Lipase(LPL)Deficiency Increases Plasma Lipid Level and Enhances Neointima Formation After Carotid Artery Injury in apoE Knock-out Mice 冼勋德冼勋德 刘国庆刘国庆北京大学心血管研究所北京大学心血管研究所 Candidate genes in lipoprotein metabolismLusis et al Circulation.2004Lipoprotein Lipase in the Arterial WallPentikinen

2、et al Arterioscler Thromb Vasc Biol.2002Lipoprotein Lipase in the Arterial WallPentikinen et al Arterioscler Thromb Vasc Biol.2002HypothesisLPL Arterial response to injuryhyperlipidemic conditions？A 1x2-mm strip of filter paper saturated with 10%FeCl3 solution was applied to the adventitial surface

3、of the surgically exposed carotid artery for 3.0 minutes,then removed.The surgical incision was sutured with 40 monofilament,and the animal was returned to its cage.Common carotid arteries of apoE-/-,LPL+/-(ELK)mice(A)and apoE-/-,LPL+/+(EK)mice(B)8 weeks after ferric chloride injuryneointima formati

4、on after carotid artery injury by FeCl3 for 8 weeksELKcarotid artery stained with H&EEKnoninjuredinjuredneointima formation after carotid artery injury by FeCl3 for 8 weekscarotid artery stained with H&E ELKEKnoninjuredinjuredMean Intimal and Medial Cross-sectional Areas of EK and ELK Mice 8 Weeks a

5、fter Injurymediaintimal0246810Mean Area(um2X104)EKELK*EKELKmedia2.95x10420005.98x1041000intimal4.01x10460008.15x1042000lipid deposit after carotid artery injury by FeCl3 for 8 weeksELKEKcontrol carotid artery stained with OROnoninjuredinjuredlipid deposit after carotid artery injury by FeCl3 for 8 w

6、eeksELKEKcarotid artery stained with OROnoninjuredinjuredlipid deposit after carotid artery injury by FeCl3 for 8 weeksELKEKcarotid artery counterstained with ORO and haematoxylininjurednoninjuredlipid deposit after carotid artery injury by FeCl3 for 8 weeksELKEKcarotid artery counterstained with OR

7、O and haematoxylinnoninjuredinjuredMacrophage stain for 8 weeksELKEKELKEKVon Willebrand Factor Stain for 8 weeksThe Plasma Triglyceride Levels of ELK and EK Mice Fed HCCELK-0wkEK-0wk ELK-4wks EK-4wks ELK-8wks EK-8wks0100200300ELKEKTG concentration(mg/dl)0 week4 weeks8 weeksELK（n=4）61.5211.09113.95.9

8、8270.1724.29EK（n=3）53.9618.1761.613.1485.079.40P value0.760.00150.0016*NSThe Plasma Total Cholesterol Levels of ELK and EK Mice Fed HCCELK-0wkEK-0wk ELK-4wks EK-4wks ELK-8wks EK-8wks02505007501000ELKEKTC concentration(mg/dl)0 week4 weeks8 weeksELK(n=4)395.534.89718.740.52939.3246.67EK（n=3）239.659.77

9、530.759.52686.0856.66P value0.0970.040.018NS*The Plasma Glucose Levels of ELK and EK Mice Fed HCCELK-0wkEK-0wk ELK-4wks EK-4wks ELK-8wks EK-8wks050100150ELKEKGLU concentration(mg/dl)0 week4 weeks8 weeksELK(n=4)118.37.9164.546.10109.74.46EK(n=3)85.1917.7461.613.14109.532.90P value0.190.680.98Animal B

10、ody Weight of ELK and EK Mice Fed HCCELK-0 wkEK-0 wk ELK-4 wks EK-4 wks ELK-8 wks EK-8 wks0102030ELKEKAnimal Body Weight(g)0 week4 weeks8 weeksELK17.750.7821.381.4521.752.18EK19.750.8822.630.7524.670.60P value0.140.470.32NSNSNSEKELKneointima formation after carotid artery injury by FeCl3 for 4 weeks

11、carotid artery stained with H&E lipid deposit after carotid artery injury by FeCl3 for 4 weeksELKEKcarotid artery counterstained with ORO and haematoxylinPAI-1LPL+/+LPL-/-0.000.010.020.03LPL+/+LPL-/-Relative mRNA expression(PAI-1/actin)ReferenceMary Beth DeYoung,Clifford Tom,David A.Dichek,et al Pla

12、sminogen Activator Inhibitor Type 1 Increases Neointima Formation in Balloon-Injured Rat Carotid Arteries.Circulation.2001;104:1972-1977Koichi Kaikita,Agnes B.Fogo,Lijun Ma,John A.Schoenhard,Nancy J.Brown,Douglas E.Vaughan,et al Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and

13、Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition.Circulation.2001;104:839-844Yanhong Zhu,Peter M.Farrehi,William P.Fay,et al Plasminogen Activator Inhibitor Type 1 Enhances Neointima Formation After Oxidative Vascular Injury in Atherosclerosis-Prone Mice.Circulation.2001;1

14、03:3105-3110Marianne Pynn,Katrin Schfer,Stavros Konstantinides,Martin Halle,et al Exercise Training Reduces Neointimal Growth and Stabilizes Vascular Lesions Developing After Injury in Apolipoprotein EDeficient Mice Circulation.2004;109:386-392Future WorksPAI-1LPLNeointima formation？Other Pathways？Thank You！