ABSTRACT
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.
ABSTRACT
ObjectiveToestablisharatmodelofatherosclerosiscombinedwithsyndromeofintermingledphlegm and blood stasis , to observe the inflammatory reactions and the treatment effect of prescription ( Danlou tablet ) on the rat model.Methods Thirty-two healthy male SD rats were randomly and equally divided into four groups , namely, normal control group, model control group, atorvastatin group (ATV group), and Danlou group (DLP group).The normal control group was given basic forage , while other three groups were given high fat forage plus intraperitoneal injection of vitamin D 3 and balloon injury of the left common carotid artery to build rat atherosclerosis model combined with syndrome of intermingled phlegm and blood stasis , and then received intragastric administration of saline , atorvastatin suspension and Danlou tablets suspension for 4 weeks, respectively.After intervention, both serum lipid and hs-CRP, IL-6, TNF-α, and LP-PLA2 levels were determined by ELISA , pathological alterations in the thoracic aorta was analyzed using HE staining , the expressions of IL-6, TNF-αand LP-PLA2 mRNA in the thoracic aorta tissue were assessed by real-time fluorescent quantitativePCRtechnology.Results ①Comparedwiththenormalcontrolgroup,thereweresignificantincreasesin serum TC, LDL-C, hs-CRP, IL-6, TNF-α, and LP-PLA2 levels (P0.05).There were also reduced aortic intimal hyperplasia , macrophage infiltration and plaque area compared with those of the model group .Conclusions Rat model of atherosclerosis combined with syndrome of intermingled phlegm and blood stasis can be established by high fat diet feeding combined with the intraperitoneal injection of vitamin D 3 and balloon injury of carotid artery .The prescription ( Danlou tablet ) can inhibit the inflammatory reaction and ameliorate atherosclerotic changes in the rat models .