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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 urotensinⅡ (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.
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Objective To investigate the total flavones of rhododendra(TFR) on contractility of rat myocardial cells and its possible mechanism. Methods The contraction amplitude and contraction frequency of primary cultured rat myocardial cells were observed by image analysis system. The intracellular free Ca2 + content was measured by calcium ion imaging system. Results 10 and 100 nmol /L hU Ⅱ significantly accelerated the contraction frequency of myocardial cells,and 10 nmol /L hU Ⅱ increased the contraction amplitude of myocardial cells,but 100 nmol /L hU Ⅱ reduced the contraction amplitude of myocardial cells. TFR 300 mg /L significantly slowed the contraction frequency of rat myocardial cells and increased the contraction amplitude. TFR in the range of 33. 3 ～ 300 mg /L could significantly inhibit the increase of contraction frequency,the decrease of contraction amplitude and the increase of intracellular free Ca2 + content induced by 100 nmol /L hU Ⅱ. Conclusion TFR can slow down the contraction frequency of myocardial cells and increase its contractility,which may be related to the decrease of free Ca2 + content in myocardial cells.
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Urotensin Ⅱ (UⅡ) and urotensin Ⅱ receptor (UTR) have significant effects on the pathogenesis of type 2 diabetes (T2D). UTR, as a G protein-coupled receptor (GPCR), mediates UⅡ signal transduction.The gene polymorphism of UⅡ and UTR is high related to the susceptibility of diabetes, suggesting a relationship between UⅡ system and T2D. UⅡ system can influence the process of T2D by affecting body weight, lipid and glucose metabolism and inflammatory response. UⅡ can also induce insulin resistance by regulating insulin-related signaling pathway or accelerating oxidative stress.Therefore, UⅡ system might be a potential target for T2D treatment.
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Objective To investigate the effect of urotensin Ⅱ on myocardial fibrosis in rats.Methods The pressure overload animal model was established in rats by abdominal aorta coarctation.The rats were divided into sham operation group,modeled for 4,8 and 12 weeks group.The expression of U Ⅱ,GPR14,col-Ⅰ,col-Ⅲ,and PKA in cardiac tissues was detected by Western blot.Isolated and cultured cardiac myofibroblasts (CFs) from new-born SD rats were treated with U Ⅱ,KT5720 or SB-611812,and then the proliferation of CFs was observed by micro scope and CKK-8.Results The expression of U Ⅱ,GPR14,col-Ⅰ,col-Ⅲand PKA increased markedly in cardiac tissues of model rat,which were time-dependent.U Ⅱ promoted the proliferation of CFs (P＜0.05),which could be inhibited by KT5720 or SB-611812.Conclusions U Ⅱ/UT system promotes the occurring and development of myocardial fibrosis.
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Objecitve:To investigate effects of urotensin Ⅱ( UⅡ)/UT system on innate immune inflammatory signal pathway TLR4-IRF3 in the lipopolysaccharide (LPS)-stimulated Kupffer cells (KCs).Methods: Rat KCs were isolated and cultured.Pro-in-flammatory cytokines including IL-6,IFN-βand IFN-γwere assayed by ELISA in culture supernatant of KCs.Cell surface TLR4 were tested with flow cytometry technique.Expression of IRF3 were tested with real-time PCR and Western blot.Results: Significant increases were showed in IL-6, IFN-βand IFN-γsecretion, TLR4-expressed positive rates and IRF3 mRNA levels in KCs after stimulated by LPS,but were inhibited via urantide pretreatment.In addition,LPS induced upregulation of nuclear IRF3 protein and downregulation of cytoplasm IRF3 protein in KCs,which were blocked by urantide pretreatment.Conclusion:UⅡ/UT system mediates immune inflammatory response in part through activating TLR 4-IRF3 pathway in LPS-stimulated KCs.
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Objective To evaluate the effect of a vasoactive substance urotensin Ⅱ on the expression of type Ⅰ collagen and migration of human skin fibroblasts,and to explore the underlying mechanisms of signal transduction.Methods Fibroblasts were isolated from human foreskin tissues and subjected to primary culture.After a series of subculture,fibroblasts were classified into several groups to be treated with different concentrations (10-10 to 10-6 mol/L) of urotensin lⅡ for 24 hours,urotensin Ⅱ of 10-s mol/L for different durations (0,4,12,24 hours),or pretreated with PD98059 (a mitogen-activated protein kinase kinase inhibitor),nicardipine (a calcium channel blocker) and ciclosporin (a calcineurin inhibitor) of 10-5 mol/L respectively for 30 minutes followed by treatment with urotensin Ⅱ of 10-8 mol/L for 24 hours.The cells receiving no treatment served as the control.Subsequently,enzyme-linked immunosorbent assay was performed to determine the level of urotensin Ⅱ in the supernatant of fibroblasts,and Transwell assay to estimate the migration activity of fibroblasts.Statistical analysis was carried out by t test and analysis of variance.Results Urotensin Ⅱ promoted the expression of type Ⅰ collagen in a time-and concentrationdependent manner.The level of type Ⅰ collagen was increased by 21.2％ (P ＞ 0.05),52.2％ (P ＜ 0.05),84.4％ (P ＜0.05),83.6％ (P ＜ 0.05) and 77.1％ (P ＜ 0.05) in the supernatant of fibroblasts treated with 10-10,10-9,10-8,10-7 and 10-6 mol/L of urotensin Ⅱ for 24 hours respectively,by 23.2％ (P ＞ 0.05),69.5％ (P ＜ 0.05) and 84.1％ (P ＜0.05) in the supernatant of fibroblasts treated with urotensin Ⅱ of 10-8 mol/L for 4,12 and 24 hours respectively,compared with the untreated control fibroblasts.The migration activity was markedly enhanced in fibroblasts treated with urotensin Ⅱ of 10-8 mol/L for 24 hours compared with the control fibroblasts (P ＜ 0.05).PD98059,nicardipine and cyclosporin A inhibited the secretion of type Ⅰ collagen by 18.2％,15.9％ and 19.7％ respectively,and suppressed the migration of fibroblasts by 38.3％ (P ＜ 0.05),20.7％ (P ＜ 0.05) and 81.4％ (P ＜ 0.05) respectively in the groups receiving pretreatment compared with those treated with urotensin Ⅱ alone.Conclusions Urotensin Ⅱ can promote the secretion of type Ⅰ collagen by and migration of fibroblasts,which may be realized through the Ca2+,calmodulin kinase,and mitogen-activated protein kinase pathways.
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Objective To investigate the effects of urotensin Ⅱ/urotensin Ⅱreceptor ( UⅡ/UT) system on the expression of inflammatory signal molecules p 38 mitogen-activated protein kinase ( p38 MAPK) and nuclear factor-κB ( NF-κB ) in lipopolysaccharide ( LPS )-stimulated Kupffer cells ( KCs ) . Methods Rat KCs were isolated and purified by means of in situ perfusion and density gradient centrifuga-tion.The isolated cells were randomly divided into six treatment groups including group 1:UⅡ(-) urantide (-)LPS(-), group 2:UⅡ(+)urantide(-)LPS(-), group 3: UⅡ(-)urantide(+)LPS(-), group 4:UⅡ(-)urantide(-)LPS(+), group 5:UⅡ(+) urantide(-) LPS(+) and group 6:UⅡ(-)urantide(+) LPS(+) .Western blot assay was performed to detect p 38 MAPK/p-p38 MAPK protein and NF-κB p65 sub-unit.The DNA-binding activity of NF-κB was tested by electrophoretic mobility shift assay (EMSA).Re-sults There was no significant difference with the expression of p 38 MAPK protein in KCs among the six groups (P>0.05).The expression of p65 protein and p-p38 MAPK and the DNA-binding activity of NF-κB were significantly enhanced in LPS-stimulated KCs from groups 4, 5 and 6 in comparison with those in group 1 (P0.05), but that were decreased in group 6 than those in group 4 (all P<0.01).Conclusion UⅡ/UT system participated in the activation of p38 MAPK and NF-κB signaling pathways in LPS-stimulated primary Kupffer cells .
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Objective To study the relationship between essential hypertension(EH)with serum homocysteine(HCY),uroten-sinⅡ(UⅡ),angiotensin converting enzyme(ACE)and N-terminal pro-brain natriuretic peptide(NT-proBNP).Methods By collec-ting the clinical cases,UⅡwas determined by ELISA and HCY,ACE and NT-proBNP were simultaneously detected by ELISA.The detection results were analyzed and compared between the patients with essential hypertension(EH group)and the healthy con-trols.Results The levels of serum HCY,UⅡ,ACE and NT-proBNP in the EH group were significantly increased compared with the healthy control group;the area under curve (AUC)of serum HCY,UⅡ,ACE and NT-proBNP in the ROC curve in the EH group were 0.93,0.765,0.792 and 0.972 respectively,which showed clinical diagnostic significance.Conclusion The levels of HCY,UⅡ,ACE and NT-proBNP are highly expressed in EH and have significant differences compared with the healthy popula-tion,which has the diagnostic value to EH.
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ObjectiveTo investigate the expression of urotensin Ⅱ(UⅡ) in the lung cancer tissue from surgical resection of lung cancer patients,and to detect the relationship between UⅡ expression and pathologie types and the clinical stages of lung cancer.MethodsThe expression rates of UⅡof 45 lung cancer tissues and 20 inflammatory pseudotumor were measured by immunohistochemical assay,and the relationship between UⅡ expression and the pathologic types and clinical stages of lung cancer was analyzed.ResultsUⅡwas mainly distributed in lung cancer cell cytoplasm,which was tan-yellow particles.The positive expression rate of UⅡin nonsmall cell lung cancer was 61.3％ (19/31),which was higher than that in small cell lung cancer(7.1％,1/14)and pulmonary inflammatory pseudotumor( 15.0％,3/20) (P ＜ 0.01 ).The positive expression rate of UⅡ was 100％ in adenocareinoma.The positive expression rate of UⅡin staging Ⅲ non-small cell lung cancer( 85.7％ )was higher than that of staging Ⅰ ( 16.7％ ) ( P ＜ 0.05).ConclusionUⅡ cxists in the cytoplasm of lung cancer cells,and the expression of UⅡis correlated with the pathological type and TNM staging of lung cancer.
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Objective To examine the correlation between urotensin Ⅱ (UⅡ) concentration and the severity of liver fibrosis. Methods Liver fibrosis model was induced in rats by intraperitoneal administration of CCl4. At 4,6,8 weeks, the rats were sacrificed, and the hepatic tissue hydroxyproline (HYP) content was measured. Hepatic tissue specimens were histopathologically evaluated according to a fibrosis scoring system. Plasma UⅡ levels were measured by ELISA method. Results Plasma UⅡ gradually increased with the increase of duration of CCL4, UⅡ concentration correlated to liver fibrosis ( R2 = 0.875, P ＜ 0.05) and hepatic HYP( R2 = 0.65, P ＜0.05). Conclusion UⅡ was involved in the pathogenesis of liver fibrosis.
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Objective To evaluate the plasma levels of adrenomedullin (ADM) and urotensin Ⅱ ( U-Ⅱ ) in children with capillary bronchiolitis, and their clinical significance. Methods One hundred and fifty three children with capillary bronchiolitis and 36 healthy children were recruited. Plasma levels of ADM and U- Ⅱ were measured at acute stage ( <7days) and convalescent stage (>14days) of airway inflammation. The relationship of plasma ADM and U-Ⅱ levels with symptom scores was evaluated. Results Plasma levels of ADM and U-Ⅱ in acute stage of capillary bronchiolitis were significantly higher than those in convalescent stage and healthy controls ( ADM: t = 20. 57 and 26. 26, P < 0. 01; U-Ⅱ: t = 14. 27 and 7. 61, P < 0. 01 ) , and there were significant differences among mild, moderate and severe capillary bronohiolitis (F = 245. 94 and 304. 79, P <0. 01). Plasma level of U-Ⅱ in convalescent stage of capillary bronchiolitis was lower than that of healthy controls (t = 6. 99, P <0. 01 ) , but ADM was still in a higher level ( t = 8. 98, P < 0. 01 ). In the convalescent stage, there was significant difference on U-Ⅱ levels among mild, moderate and severe capillary bronchiolitis ( F = 25.69, P < 0. 01 ) , but no significant difference was observed for ADM levels (F = 2. 25 , P > 0. 05 ) . Plasma levels of ADM and U- Ⅱ in acute stage showed positive correlation with symptom scores, and the regression coefficients were 0.884 (P =0. 000) for ADM and 0. 943 (P = 0. 000) for U-Ⅱ . Conclusion Plasma ADM and U-Ⅱ levels in children with capillary bronchiolitis are increased in acute stage and correlated with the symptom scores, which may serve as laboratory indicators for assessing the severity of the disease.
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Aim To investigate the effect of urotensin Ⅱ on vascular calcification.Methods Calcified VSMCs of rat in vitro were induced by β-glycerophosphate.Cellular calcium content,ALP activities,~(45)Ca accumulation and osteocalcin content were measured.Results Compared with those of control group,calcium content,ALP activities,~(45)Ca uptake and osteocalcin in calcified VSMCs increased greatly(P<0.01).Calcium content,ALP activities,~(45)Ca uptake and osteocalcin of calcified VSMCs stimulated by urotensin Ⅱ (10~(-10)、10~(-9) and 10~(-8) mol·L~(-1))were greatly increased in a concentration-dependent manner as compared with those of calcified group(P<0.01).Conclusion UrotensinⅡ aggravates the calcification of VSMCs induced by β-glycerophosphate.
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Objective To determine the plasma urolensin Ⅱ(UⅡ) levels in various types of coronary heart disease and to clarify how the plasma UⅡ levels correlate with the clinical presentation, extent and severity of coronary artery atherosclerosis (CAD). Methods: One hundred and three aged patients undergoing elective diagnostic coronary angiography for proven or clinical suspected coronary heart disease were enrolled in this study. The extent and severity of coronary artery disease were evaluated by vessel score and Gensini score, respectively. Plasma UⅡ levels were measured by radioimmunoassay. Results: The plasma UⅡ levels in the patients with modest to severe coronary stenosis (3.03±0.34 pg/ml, 1.83±0.67 pg/ml) were significantly lower than that in subjects with normal coronary artery (4.80±1.11 pg/ml, P＜0.001). The plasma UⅡ levels in patients with coronary heart disease were also significantly lower than that in patients with insignificant coronary stenosis (P ＜ 0.001). Compared to patients with stable angina pectoris, plasma UⅡ levels in patients with acute coronary syndrome were significantly decreased (1.89±0.51 pg/ml vs 2.42±0.77 pg/ml, P＜ 0.001). Plasma UⅡ levels were found to be negatively correlated with the severity of coronary artery stenosis (r = -0.488, P＜0.001), as well as the vessel score (r = -0.408, P＜0.05) in the patients with CAD. Conclusion: Significant inverse correlations exist between the plasma UⅡ levels, and the extent and severity of coronary artery stenosis. These findings suggest that plasma UⅡ contribute to the development and progression of coronary artery stenosis, and may be a novel marker to predict clinical types, as well as the extent and severity of coronary artery disease in the patients.
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Objective The goal of this study was to examine the association between urotensin Ⅱ (U Ⅱ) concentration and the severity of coronary artery disease (CAD). Methods We studied U Ⅱ concentrations in 100 patients with known or suspected CAD referred for cardiac catheterization. Based on coronary angiograms, subjects were classified as having no or mild CAD (stenosis ＜50%) and significant CAD (stenosis=50%). Micheal score system was used to estimate the severity of CAD. Result U Ⅱ concentration in the significant CAD group had no difference compared with the no or mild CAD group (1.95±1.18 pmol/L vs 2.04±1.47 pmol/L, P＞0.05),but higher in the severe group (score =9) than in the normal or nearly normal group (score＜3)( 2.50±1.62 pmol/L vs 1.61±1.05 pmol/L,P=0.03). U Ⅱ concentration had no relationship with other known risk factors, but it correlated with CAD severity (r=0.213, P=0.034).In multiple regression analysis, U Ⅱ is one of the determinants of the severity of CAD, other than age, abnormal glucose, hypertension and gender. Conclusios U Ⅱ is elevated in severe CAD and there is a significant relationship between U Ⅱ concentration and CAD severity.
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Objective To investigate the alteration of urotensin Ⅱ in plasma of acute lung injury(ALI)rats,which affected by the urotensin Ⅱ receptor antagonist(URA),and to study the function of URA to ALI.Methods Forty-two Sprague Dawley(SD)rats were divided into two groups randomly,with each containing 21 rats.All rats were injected with oleic acid for ALI models.G1 as ALI model group,the other group was injected with URA as experiment group(G2).2 ml blood was drawn in 3,12,24 hours after injection,with each time blood being drawn in seven rats of each group.Plasma was separated from the blood.Keep plasma in-80℃ to be detected.Results The concentration of UⅡ of G1 in 3,12,24hours was(105.57?9.52)pg/ml,(119.30?8.30)pg/ml,(133.33?9.65)pg/ml,respectively;and(133.65?8.89)pg/ml,(131.99?9.80)pg/ml,(114.03?9.12)pg/ml in the same time of G2.With the time going on,the plasma concentration of UⅡwas significantly increased(P
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Objective To investigate the effects of urotensinⅡ(UⅡ)receptor antagonist(URA)on UⅡ in plasma and bronchoalveolar lavage fluid(BALF)in rats with acute lung injury(ALI).Methods Twenty eight Sprague Dawley(SD)rats were randomly divided into four groups:saline control group(group A),the other three groups(group B,group C,group D).Rats were injected with oleic acid and URA to produce ALI models.Three hours after injection,arterial blood was drawn for blood gas analysis in all rats.Immediately after this,blood of heart was collected in group A and group B.Then blood of heart were collected after 12 hours in group C and after 24 hours in group D.Rats were killed when blood of heart was drawn.Bronchoalveolar lavage(BAL)with saline was performed in the right lung.BALF was centrifugated and the upper fluid was put to the EP tube.Plasma was separated from the blood of heart.Both plasma and BALF were kept at -80 ℃ to be determined.Results Compared with group A,arterial pressure of oxygen was significantly decreased in the group B,group C,group D(P
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Objective To investigate the effects of Urotensin Ⅱ(UⅡ)on proliferation of rat pheochromocytoma cell line(PC12) and primary cultured human pheochromocytoma cells.Methods We observed the effects of UⅡ on the proliferation of rat PC12 cells and human pheochromocytoma cells in vitro by MTT method.Results 1.UⅡ had no obvious effect on the proliferation of rat PC12 cells.2.UⅡ(at 10-7 and 10-6mol/L) promoted the proliferation of primary cultured human pheochromocytoma cells. Conclusion UⅡ stimulates the proliferation of human pheochromocytoma cells and probably plays a role in the pathogenesis of pheochromocytoma.
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Objective To investigate the roles of urotensin Ⅱ(U-Ⅱ) in rat with chronic obstructive pulmonary disease(COPD).Methods Male SD rats were randomly divided into chronic bronchitis group(group B),COPD group(group C),exsmoker group(group D) and control group(group A). The concentrations of U-Ⅱ in plasma,BALF and lung tissues were measured by RIA.Lung function and pathological analysis of lung specimens were performed.Results There was no significant difference of plasma U-Ⅱ levels among groups.The BALF levels of U-Ⅱ was 1.7,2.2,4.7,4.9 folds higher than plasma levels in group A,B,C and D respectively(all(P
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UrotensinⅡis the earliest active peptide detected from the teleost fish spinal cord, which is correlated with various risk factors of cerebrovascular diseases.This article reviews the latest advances in reasearch on urotensinⅡin cerebrovascular diseases,so as to provide assistance for urotensinⅡin the prevention and treatment of cerebrovascular diseases.
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Objective To observe the levels of plasma and urinary urotensin Ⅱ in patients with Type 2 diabetes mellitus (DM)and to investigate the influence of renal impairment and other involved clinical or laboratory feature on them. Methods The 42 patients with type2 patients were divided into three groups according to their correctional clearance of creatinine(Ccr):Group A(n=14)with Ccr≥70 mL/min; group B(n=18)with 30≤Ccr