Role of vascular remodeling for urotensin Ⅱ in rat thoracic aorta after balloon injury

AIM: To explore the possible effect of UII in the process of remodeling after vascular injury. METHODS: The rat model of balloon injury in thoracic aorta was established. Male rats were randomized to 4 groups (n=5), including sham injury group, injury group, UII group (UII pumped into the rats after thoracic aorta balloon injury at 1.0 nmol·kg-1·h-1) and urantide group (urantide pumped into the rats after thoracic aorta balloon injury at 10 nmol·kg-1·h-1). At 21 days, the thoracic aortas were taken out to measure the changes of pathology, the expression of UII, the proliferation of VSMC and the expression of collagen. RESULTS: (1) At the 21 days after operations, the systolic blood pressure was higher in UII group than that in injury group ［(140.0±10.0) mmHg vs (132.0±3.4) mmHg, P>0.05］. The systolic blood pressure was also obviously higher than that in urantide group ［(140±10.0) mmHg vs (128.0±2.4) mmHg, P<0.05］. (2) Urotensin Ⅱ was expressed strongly in the injured area after thoracic aorta injury. (3) In contrast to injury group, the intimal thicken in urotensin Ⅱ group enhanced, the decrease in lumen area was marked (0.13±0.05 vs 0.07±0.02, P<0.05), the cell proliferation index was markedly increased (0.74±0.16 vs 0.40±0.11, P<0.01), and the expression of collagen was also markedly increased (counted as IOD, 318±127 vs 78±26, P<0.01). (4) In contrast to injury group, the decrease in lumen area was not abolished (0.09±0.03 vs 0.07±0.02, P>0.05) after chronic infusion of urotensin Ⅱ receptor antagonist urantide, the cell proliferation index was markedly increased (0.73±0.15 vs 0.40±0.11, P<0.01) and the expression of collagen was not statistically increased (counted as IOD, 200±79 vs 78±26, P>0.05). CONCLUSION: Urotensin Ⅱ expresses strongly in the myointimal cells after thoracic aorta injury in rat. The extra UII enhances the proliferation of VSMC and expression of collagen in the myointimal, increases the stenosis of injured vasculature, indicating that UII might take part in the process of repairing after vessel injury.     

Effect of urantide on liver function and histomorphology in atherosclerotic rats

AIM:To investigate the effect of urantide on the liver function and histomorphology in the rats with atherosclerosis (AS).METHODS:The AS Wistar rat model was induced by intraperitoneal injection of vitamin D₃ (VD₃) and feeding with high-fat diet. The rats were randomly divided into normal control group, AS model group, positive medicine group and urantide group. The liver function indexes of the rats were measured by biochemical test, and the pathological changes of the aorta and liver of the rats were observed by hematoxylin-eosin (HE) staining. The mRNA expression of urotensin Ⅱ (UⅡ) and GPR14 at mRNA and protein levels in rat livers was determined by RT-qPCR and Western blot. RESULTS:The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), lactate dehydrogenase (LDH), total bilirubin (TBIL), indirect bilirubin (IBIL) and alkaline phosphatase (ALP) in AS model group were significantly increased compared with normal control group (P<0.05). The above indexes in urantide group were remarkably decreased compared with AS model group (P<0.05). No change of the levels of direct bilirubin (DBIL), total protein (TP), globulin (GLB) and albumin (ALB) in each group was observed. Urantide postponed hepatocyte fatty degeneration and repaired hepatocyte injury in the AS rats. Compared with normal control group, the mRNA and protein levels of UⅡ and GPR14 in the liver were significantly increased in AS model group (P<0.05). With the prolongation of dosing time, the mRNA and protein levels of UⅡ and GPR14 in the liver were significantly decreased in urantide group compared with AS model group (P<0.05). CONCLUSION:Urantide significantly attenuates the liver damage caused by liver fatty degeneration in AS rats.