Abstract: Objective: To investigate the effects of urantide on the expressions of type Ⅳ collagen(Col Ⅳ) in thoracic aorta and vascular smooth muscle cells(VSMC) in the rats with atherosclerosis(AS), and to clarify its mechanism of prevention and treatment of AS.Methods: A total of 180 Wistar rats were randomly divided into normal control group (n=30) and AS model group (n=150).The rat models of AS were established by feeding on high-fat diet or intraperitoneally injecting vitamin D₃(VD₃).The AS model rats were randomly divided into AS group, fluvestation(Flu) group and urantide group (3, 7, and 14 d groups).The expression of Col Ⅳ in thoracic aorta wall of the rats was detected by immunohistochemistry.The levels of hydroxyproline (HYP) in serum and urine of the rats in various groups were measured by ELISA.The VSMC were randomly divided into normal control group, urotensin Ⅱ(UⅡ 10^-8mol·L^-1) group, Flu group and urantide (10^-10to 10^-6 mol·L^-1) groups.The levels of Col Ⅳ in VSMC of the rats in various groups were determined by ELISA.Results: There was a significant difference in the expression levels of Col Ⅳ in the irregular plaques of the thoracic aorta of the rats between various groups (F=35.09,P<0.01). The expression levels of Col Ⅳ in thoracic aorta of the rats in AS group were significantly increased compared with normal control group (P<0.01); the intensity and extent of Col Ⅳ positive staining in urantide group were lower than those in AS group (P<0.01).There were significant differences in the serum and urine HYP levels between various groups (F=24.38, P<0.01;F=26.72,P<0.01). Compared with normal control group, the serum HYP level of the rats in AS group were significantly increased (P<0.01), and the urine HYP level was significantly decreased (P<0.01).Compared with AS group, the serum HYP levels in urantide groups were significantly decreased (P<0.01) and the urine HYP levels were significantly increased (P<0.01), no less than the level in Flu group.The expression levels of Col Ⅳ in the culture supernatant of VSMC in the rats in various groups had significantly difference (F=31.04,P<0.01).The expression level of Col Ⅳ in the culture supernatant of VSMC of the rats in UⅡ group was significantly increased compared with normal control group (P<0.01); the expression levels of Col Ⅳ in the culture supernatant of VSMC of the rats in urantide groups were significantly decreased compared with UⅡ group(P<0.05 or P<0.01).Conclusion: Urantide can inhibit the expressions of Col Ⅳ in the thoracic aorta and VSMC of the AS rats and alleviate the degree of AS lesions, which provides the experimental evidence for the clinical application of urantide in the treatment of AS.

Key words: atherosclerosis, urotensinⅡ, urantide, vascular smooth muscle cells, type Ⅳ collagen