AIM: To observe the inhibitory effect of recombinant human endostatin (rhES) on plaque angio-genesis, and to explore the regulatory mechanism of Dll4 /Notch pathway in the anti-angiogenic effect of rhES.METH-ODS: Male Wistar rats were randomized into 3 groups: normal control group (N group), atherosclerotic model group (AS group), and rhES treated group (AS +rhES group).The rats in N group were fed a normal diet, while the remaining 2 groups were established to atherosclerotic rat model via high-cholesterol diet, intraperitoneal injection of vitamin D3 and aor-tic balloon injury.The rats in AS +rhES group received intraperitoneal injection of rhES.The blood total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-1 (IL-1) and troponin I (TnI) were measured.The atherosclerotic abdominal aortas were taken for pathological observation.Immu-nohistochemical staining was used to measure the density of neovessels in the plaques, which were marked by CD31.The protein levels of Dll4 and Notch1 in the aortas were analyzed by Western blot.RESULTS: The levels of blood TC, TG, LDL-C, CRP and IL-1 in AS group and AS +rhES group were much higher than those in N group (P <0.05), and no sta-tistical difference between AS group and AS +rhES group was observed.The expression of CD31 in AS group was the high-est among all groups.Compared with AS group, the density of neovessels in the plaques of AS +rhES group decreased sig-nificantly (P <0.05).The protein expression of Dll4 and Notch1 in AS group was lower than that in N group (P <0.05). Compared with AS group, the protein expression of Dll4 and Notch1 increased significantly (P <0.05).CONCLUSION:rhES has the ability to inhibit plaque angiogenesis in rats.The activation of Dll4 /Notch pathway may be the mechanism of rhES in inhibiting plaque angiogenesis.%目的：观察重组人内皮抑素（rhES）对大鼠动脉粥样硬化（AS）斑块内新生血管的抑制作用，探讨Dll4／Notch 信号通路在其中的调控机制。方法：雄性 Wistar 大鼠随机分为正常对照组（N 组）、AS 组和 AS ＋rhES组，每组10只。 N 组始终喂基础饲料，其余2组采用高脂喂养、维生素 D3负荷及球囊损伤动脉内膜建立大鼠 AS模型。 AS ＋rhES 组以10 mg・ kg －1・ d －1的 rhES 腹腔注射4周，另2组注射等量生理盐水。采血检测各组的总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL－C）、C 反应蛋白（CRP）、白细胞介素－1（IL－1）和肌钙蛋白 I （TnI）等；免疫组化 CD31染色观察新生血管密度；Western blot 法检测主动脉内 Dll4、Notch1蛋白表达。结果：与 N组比较，AS 组和 AS ＋rhES 组的 TC、TG、LDL－C、CRP 和 L－1水平均显著升高（P ＜0．05），但上述指标在 AS 组和 AS＋rhES 组之间差异无统计学显著性。 CD31染色结果显示，AS 组的新生血管表达最丰富；与 AS 组比较，AS ＋rhES组的新生血管密度显著下降（P ＜0．05）。 AS 组的 Dll4和 Notch1蛋白水平显著低于 N 组（P ＜0．05）；相比 AS 组， AS ＋rhES 组的 Dll4和 Notch1蛋白水平显著升高（P ＜0．05）。结论： rhES 能够抑制大鼠 AS 斑块内血管新生，Dll4／Notch 通路的激活可能是 rhES 抑制斑块内的血管新生的信号机制。
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