ABSTRACT
Objective: To observe the endothelial-dependent vasodilatation and expressions of cyclophilin A (CyPA), phosphorylated extracellular signal regulated kinase1/2 (p-ERK1/2) in experimental rats with obesity combining atherosclerosis. Methods: A total of 30 male Wistar rats were randomly divided into 3 groups:Control group, the rats received basic diet followed by intraperitoneal injection of normal saline;Atherosclerosis (AS) group, the rats received basic diet for 8 weeks followed by high cholesterol diet with intraperitoneal injection of a single dose vitamin D3 600,000 IU/kg; Obesity+AS group, the rats received high cholesterol diet for 8 weeks (which made their body weights at 20%higher than the other 2 groups) followed by intraperitoneal injection of a single dose vitamin D3 600,000 IU/kg. n=10 in each group. 16 weeks later, the endothelial-dependent vasodilatation was examined in all rats, expressions of CyPA and p-ERK1/2 in arterial wall were detected by HE staining and immunohistochemistry. Results: Compared with Control group, both AS group and Obesity+AS group had reduced endothelial-dependent vasodilatation (72.49 ± 3.27)%and (42.28 ± 2.62)%vs (96.63 ± 3.85)%, such reduction was even more in Obesity+AS group (42.28 ± 2.62)%vs (72.49 ± 3.27)%, all P Conclusion: The rats with obesity and AS had decreased endothelial-dependent vasodilatation, severe atherosclerosis and calciifcation plaques, increased expressions of CyPA and p-ERK1/2, which speculated that obesity might be an independent risk factor for atherosclerosis.
ABSTRACT
Objective: To observe the changes of endothelial-dependent vasodilatation and cyclophilin A (CyPA) expression at different phases of atherosclerosis in experimental rats. Methods: A total of 30 male Wistar rats were divided into 4 groups: Control group, the rats received normal diet, and 3 atherosclerosis groups, the rats received high cholesterol diet for different period of time and a single dose intraperitoneal injection of Vitamin D3 at 600,000 IU/kg, as Atherosclerosis at 8 weeks (AS 8W) group, AS 12W group and AS 15W group, n=8 in each AS group. The rats were sacriifced at the same time to isolate aorta abdominalis. The expression of CyPA at the wall of aorta abdominalis was detected by HE staining and immunohistochemistry. In addition, the aorta abdominalises was cut into 5 mm rings to observe its response to acethylcholine in exvivo organ bath. Results: With prolonged modeling time, the rats at different groups presented normal vessel structure, endothelial cell damage, vessel smooth muscle cell proliferation, atherosclerosis plaque formation and calciifed plaque formation for differentpathological characteristics. The endothelial-dependent vasodilatation was decreased and the maximum vasodilatation percentage in Control group, AS 8W group, AS 12W group and AS 15W group were at (93.46 ± 2.80) %, (82.58 ± 3.25) %, (61.19 ± 3.72)% and (41.28 ± 2.68)% respectively,P<0.05 between each group. The CyPA expression in endothelial cell and vessel smooth muscle cell were increased accordingly in 4 groups by OD value as (0.25 ± 0.06), (0.34 ± 0.09), (0.53 ± 0.09) and (0.68 ± 0.13) respectively,P<0.05 between each group. Conclusion: The CyPA expression increased and the endothelial-dependent vasodilatation decreased with the progress of atherosclerosis accordingly in experimental rats. The expression level of CyPA is related to atherosclerosis degree and it is one of the initial factors for atherosclerosis in rats.
ABSTRACT
Objective To observe the expression changes of cyclophilin A ( CyPA ) , Krüppel-like factor 2 (KLF2),and endothelial nitric oxide synthase (eNOS) in the pathological process of atherosclerosis in rats. Methods Thirty-two male Wistar rats were randomly divided into four groups:a control group and atherosclerosis 8,12,and 15 week groups (n=8 in each group). The atherosclerosis groups were fed with high-fat diet,and they were given vitamin D3 600 000 IU for a single intraperitoneal injection,and the rats in the control group were fed with the basal feed. The rats were sacrificed at 8,12,and 15 weeks. Their abdominal aortas were separated and stained with hematoxylin-eosin staining. Immunohistochemical method was used to detect the expression levels of CyPA,KLF2,and eNOS on arterial walls. Results With the progression of atherosclerosis lesion,the rats in the control group,and atherosclerosis 8,12,and 15 week groups showed different characteristics, including normal vessel structure, endothelial cell damage, smooth muscle cell proliferation,formation of atherosclerotic plaque,and formation of calcified plaque. There were significantly differences in the expression levels of CyPA,KLF2,eNOS on vessel walls among the control group,atherosclerosis 8,12,and 15 week groups (CyPA:0. 0037 ± 0. 0018,0. 0276 ± 0. 0090,0. 0526 ± 0. 0129,and 0. 1080 ± 0. 0388;KLF2:0. 0932 ± 0. 0331,0. 0415 ± 0. 0076,0. 0207 ± 0. 0059, and 0. 0014 ± 0. 0003;eNOS:0. 0358 ± 0. 0185,0. 0148 ± 0. 0080,0. 0049 ± 0. 0025,0. 0037 ± 0. 0026;F=36. 395,42. 108,and 21. 255,respectively,all P<0. 05),and the CyPA expression showed an increasing trend among groups, and there were significant differences between the pairwise comparisons (all P<0. 05). The expression level of KLF2 showed a progressive declining trend,and there were significant differences between pairwise comparisons (all P <0. 05);there was significant difference in eNOS expression between the atherosclerosis 12-week group and the atherosclerosis 15-week group, and there were significant differences among other groups (all P<0. 05). Conclusion With the progression of atherosclerotic lesions, the expression of CyPA increases progressively, and the expression levels of KLF2 and eNOS decrease progressively. This may be one of the approaches of CyPA caused atherosclerotic lesion.