Objective To evaluate the relationship between endothelin (ET) in bile and peripheral blood with systemic and hepatobiliary injury in patients with acute cholangitis of severe type (ACST). Methods ET, ALT and total bilirubin in bile and peripheral veinous blood of 25 patients with acute cholangitis of severe type (ACST) were detected during operation, one week and two weeks after operation. Results The contents of ET, ALT and total bilirubin were significantly lower on 7-day and 14-day after operations as compared with that during operations (Ｐ＜0.05 and Ｐ＜0.01). The concentration of ET in peripheral veinous blood paralleled with that in bile. Conclusion This suggests that ET is tightly related with the pathologic process of ACST. So, in patients with ACST, the dynamic measurement of ET in peripheral veinous blood can be an index for judging the degree of pathological damage either to the hepatobiliary or systemic systems.
To investigate the effect of modified cold preservation on rat livers. The modified method was that the vascular bed of rat liver was infused with an additional 20 ml, 30 ml and 40 ml self-made HYD solution/100g liver. Via portal vein and the vesselses of liver were ligated. Forty rats were randomly divided into four groups including conventional storage group (control group) and modified preservation groups (20%, 30% and 40% group). The indices of hepatic microcirculation, enzymes level in the effluent and bile production were determined in the groups. Results: Bile production and all the indices of hepatic microcirculation including portal perfused pressure, endothelin-1 in the effluent, Trypan Blue distrubution time and histology in experimental groups were significantly superior to those in control group (Ｐ＜0.05). The liver enzymes in 30% group were markedly lower than those in control group (Ｐ＜0.05). The preservation effect of rat livers in 30% group was the best among the experimental groups. Conclusions: The modified cold storage method is effective and may have potential for clinical application for liver preservation.
Objective To study the effects of endothelin (ET) on acute pancreatitis in rats. Methods The acute edematous pancreatitis (AEP) and hemorrhagic necrotizing pancreatitis (AHNP) model of rats were induced by cerulein and dextran-110 and endothelin-1 was administered on AEP rats via intravenous injection. Serum amylase, plasma ET and 6-Keto-PGF1α, pancreas hostologic observation were determined. Results The serum concentration of amylase increased markedly in AHNP rats, and there was a significant difference between AHNP and AEP (Ｐ＜0.01). A dose of extrinsic ET-1 may induce the conversion of AEP to AHNP in rats. The degree of pancreatic damage correlates positively with the level of the plasma ET. Conclusion Endothelin might take part in the development of acute pancreatitis, and play a key role in the conversion of AEP to AHNP.
Objective To investigate the effect of the damage and functional change of vascular endothelial cells (VEC) on diabetic retinopathy(DR). Methods Circulating endothelial cell (CEC) number and plasma endothelin(ET) level were measured in 18 normal control subjects and 55 patients with diabetes mellitus (DM) consisting of 20 cases of DM with out retinopathy,20 cases of DM with-background diabetic retinopathy and 15 cases of DM with proliferative diabetic retinopathy. Results CEC number and plasma ET level in DM were significantly higher than those in normal subjects(Plt;0.001)respectively.With the progression of DR,CEC number was significantly elevated and plasma ET level was gradually elevated.There was significant positive correlation between CEC number and plasma ET level (r=0.738,Plt;0.001,n=55). Conclusion VEC damage and elevated plasma ET level induced by VEC damage may play an important role in the development and progression of DR. (Chin J Ocul Fundus Dis,2000,16:166-168)
In order to study effect of endothelin (ET-1) on hepatic blood flow in rats and effect of nitric oxide (NO) and prostacyclin (PGI2) on ET-1 biological function, 20 rats were randomized into control, ET-1, ET-1 plus nitric-Larginine, ET-1 plus prostacyclin and indomethen groups. The result showed that ET-1 decreased hepatic blood flow and lasted for longer time. NO and PGI2 may antagonize the biological action of ET-1 during endotoxemia. Therefore, the endothelium-derived vascular factors may regulate hepatic blood flow.
Objective To investigate the alteration of protein kinase C (PKC) and endothelin system in early diabetic rats, and the effect of specific PKC inhibitor on the expression of retinal endothelin-1 (ET-1). Methods The rats model with streptozotocin(STZ)-induced diabetes were set up. The expression of retinal PKC was detected by enzyme-linked immunoabsorbent assay (ELISA). The expression of retinal ET-1, ET-3, ET-A and ET-B receptor mRNA was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The alteration of retinal ET-1 mRNA after intravitreal injection of PKC inhibitor GF109203X in diabetic rats was also observed. Results The activities of membranous PKC were significantly increased in 2-week diabetic rats compared with that in normal rats（t=3.296 , P=0.008）, while activities of cytosolic PKC were unchangeable（t=0.138, P=0.894）. The expression of retinal ET-1 mRNA was significantly increased（P=0.008）, while no change was found in expression of ET-3, ET-A and ET-B mRNA（P=0.918，P=0.889，P=0.500）. After intravitreal in jection of 10-5、10-6、10-7 mol/L PKC inhibitor GF109203X in diabetic rats, the expression of retinal ET-1 mRNA was decreased in a dose-dependent manner compared with the control rats. Conclusion Activation of PKC and increased expression of ET-1 could be found in the retina of early diabetic rats, and PKC inhibitor could inhibit the expression of retinal ET-1. (Chin J Ocul Fundus Dis，2004，20：168-171)
ObjectiveTo investigate the change of renal endothelin (ET) excretion and its relation to renal dysfunctions in obstructive jaundice.MethodsSixty male Wistar rats were randomized into two groups, the common bile ducts were ligated to establish the model of obstructive jaundice in experimental group, and only sham operation was done in control group. Ten rats were taken from each group at 5, 10 and 15 days respectively after operation, renal functions were evaluated by paminohippuric acid clearance (CPAH), inulin clearance (CIN) and fractional sodium excretion (FENa+); furthermore, plasma endotoxin (EX) level was determined, and ET1 contents in renal arterial plasma, renal venous plasma and renal tissue were detected. ResultsOnly FENa+ was significantly increased at the 5th day in experimental group; since the 10th day, all the three renal functional parameters gradually decreased, and FENa+ was significantly lower than that in control group at 15th day (P＜0.01 vs control). ②The plasma EX sustained at significantly higher levels after operation in experimental group (P＜0.01 vs control). ③The renal arterial plasma ET1 was significantly decreased, while the contents in renal venous plasma and renal tissue were significantly increased after operation in experimental group (P＜0.01 vs control). ④There were positive correlation between plasma EX and renal ET1 content, negative correlation between renal ET1 content and CPAH/CIN, and positive correlation between renal ET1 content and FENa+ (P＜0.01).ConclusionThe increased excretion of renal ET stimulated by endotoxemia may play an important role in the renal dysfunctions in obstructive jaundice.
ObjectiveTo observe the concentration of plasma endothelin (ET-1) in patients with nonarteritic anterior ischemic optic neuropathy(NAION) and investigate the relationship between ET-1 and NAION.MethodsThe plasma levels of ET-1 in 41 patients with NAION and 15 age-matched normal control subjects were measured by radioimmuoassay (RIA). The patients with NAION were divided into high papilloedema group, light papilloedema group, and recovery group according to the degree of papilloedema; and were divided into group1 (within 14 days), 2 (within 15-30 days), 3 (within 31-60 days), and 4 (within 61-180 days) according to the disease course. The plasma levels of ET-1 in different groups were detected and compared.ResultsThe plasma level of ET-1 in patients with NAION was significantly higher than that in the normal subjects (t=5.02，P＜0.05）and there was no obvious difference in NAION patients with different genders.There were significant differences of the plasma level among the groups with different degree of papilloedema（F=4.65，P＜0.05）. ET-1 plasma level gradually decreased as the disease course increased, and there were significant differences among the groups with different disease course（F=4.29，P＜0.05）. The difference of plasma level of ET-1 between Group 13 with corresponding disease courses and the control group was significant respectively(t1=5.92，t2=3.47，t3=2.18， P1lt;0.01, P2lt;0.05, P3lt;0.05)ConclusionThe plasma level of ET-1 in patients with NAION may be related to the degree of papilloedema lesion and disease courses. (Chin J Ocul Fundus Dis, 2005,21:156-158)
ObjectiveTo study the effect of endothelin receptor antagonist on recent outcome of patients undergoing Fontan surgery. MethodsThirty nine patients who received Fontan procedure from January 2009 to December 2010 in Wuhan Asia Heart Hospital were recruited in the study. There were 25 males and 14 females with mean age of 8.02±4.98 years (ranged from 2.5 to 18.0 years). According to the admission number, the patients were randomly divided into an endothelin receptor antagonists group (bosentan group, n=16) and a control group (n=23). The bosentan group received bosentan treatment by gastric fill or oral according to the recommended dose in three days after surgery for over 7 days. The control group did not receive any pulmonary hypertension targeted therapy. On the 10th day after surgery, indexes including mortality etc in the two groups were compared. ResultsNo death occurred in the bosentan group. One patient died on the 5th day after operation in the control group. There was no significant difference in the postoperative mortality. The patients in the bosentan group got significantly better results than the control group in cardiac function, incidence of pleural effusion, vasoactive drugs score, and serum B-type natriuretic peptide, albumin, alanine aminotransferase on the 10th day (P < 0.05); while the 6-minute walk distance, transcutaneous oxygen saturation, white blood cell count, C-reactive protein, cardiac troponin I, and creatinine of the two groups showed no statistical difference (P > 0.05). ConclusionEndothelin receptor antagonists can improve the short-term outcome of patients after Fontan surgery.
This prospective animal study was designed to investigate the changes of plasma endothelin (ET) levels in acute necrotizing pancreatitis (ANP). Sprague-Dawley rats were randomly devided into 3 groups: acute necrotizing pancreatitis (ANP) group in which ANP was induced by infusion of 5% sodium taurocholate (STC) into biliopancreatic duct, sham operation (SO) group and platelet activating factor antagonist BN50739 (BN) group. Blood levels of ET and platelet activating factor (PAF) were detected. Pancreatic microcirculatory blood flow was measured and pancreatic histological scores were evaluated. Results showed that the pancreatic microcirculatory blood flow in ANP group was decreased to a great extent immediatly after induction of ANP and soon began to rise slowly for 3 hours and again decreased steadily after that. The blood levels of ET, PAF and histological scores in ANP group were significantly higher than those in SO group. In BN group, the blood flow was significantly improved and the levels of blood ET, PAF and histological scores were all significantly lower as compared to those in ANP group. It is concluded that ischemia/ reperfusion is present in the initiation of acute necrotizing pancreatitis induced by STC in the rat. This leads to injuries of endothelial cells and increase in the production of ET and PAF. I/R lesions,and interaction of ET and PAF lead to a vicious circle, thus augmenting the pathological changes in the pancreas.