The correlation between pulmonary endothelin receptors and alveolar-arterial oxygen gradient (A-aDO2) in rats with hepatopulmonary syndrome was investigated. Animals were divided into 2 groups: Sham-operated (Sham) group and common bile duct ligation (CBDL) group. Arterial blood gas was evaluated by a blood gas analyzer. The concentrations of ET-1 in blood and lung tissue sample were evaluated by radioimmunoassay. The distribution and expression of two kinds of subtype receptor of ET-1, ETRA and ETRB were examined by in situ hybridization. The results showed that the level of A-aDO2 was higher in CBDL group than that in Sham group (P < 0.05). The levels of plasma and pulmonary ET-1 in CBDL group were both higher than in Sham group (P < 0.05). There was no significant difference in average A of ETRA between two groups by imaging analysis (0.21 +/- 0.06 vs 0.22 +/- 0.08, P > 0.05), while that of ETRB was higher in CBDL group than in Sham group (0.58 +/- 0.16 vs 0.28 +/- 0.07, P < 0.05). The expression of ETRB in lung was positively correlated with A-aDO2 (P < 0.05). It was concluded that the widened A-aDO2 may be related with enhancement of the expression of ETRB in lung.
Endothelin-1/metabolism ; Hepatopulmonary Syndrome/*metabolism ; Lung/*metabolism ; Oxygen/*metabolism ; Pulmonary Alveoli/*metabolism ; Rats, Wistar ; Receptor, Endothelin A/metabolism ; Receptor, Endothelin B/*metabolism

OBJECTIVETo determine the lung expression of tissue factor (TF) mRNA in hepatopulmonary syndrome (HPS) using a rat model system and to investigate the potential significance of its differential expression.

METHODSForty male Sprague-Dawley rats were used to establish models of cirrhosis (n = 20) and HPS (n = 20). Blood gas analysis was used to investigate the effects of each model on pulmonary function. Effects on the expression of TF mRNA in lung were determined by qRT-PCR and on lung pathology by histological analysis.

RESULTSThe HPS rats showed significantly lower PaO2 than the cirrhosis rats (58.20 +/- 3.19 mmHg vs. 85.00 +/- 2.53 mmHg, P less than 0.05) but significantly higher TF mRNA expression in lung (0.77 +/- 0.22 vs. 0.33 +/- 0.14, P less than 0.05). TF mRNA expression was negatively correlated with the value of PaO2 (r = -0.565, P less than 0.05). The lungs of the cirrhosis rats showed widened alveolar intervals, diversified sizes of alveolar spaces, reduced lung capacity, inflammatory cell infiltration, and hyperemia in the pulmonary vessels. The lungs of the HPS rats showed all of the same changes but also with accumulated macrophages and micro-thrombosis in the pulmonary vessels. Among the HPS rats, those with micro-thrombosis in pulmonary vessels showed a greater increase in TF mRNA expression than those without (0.68 +/- 0.17 vs. 0.40 +/- 0.12, P less than 0.05).

CONCLUSIONThe expression of TF mRNA in lung of hepatopulmonary syndrome model rats was elevated and might increase the incidence of thromboembolism in the lung.

Animals ; Disease Models, Animal ; Hepatopulmonary Syndrome ; genetics ; metabolism ; Lung ; metabolism ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Thromboplastin ; genetics ; metabolism

OBJECTIVETo determine the changes in levels of D-dimer, prothrombin time (PT), fibrinogen (Fib), CD4 and CD8 in relation to hepatopulmonary syndrome (HPS) by using a rat model system and to assess the association with pathologic changes in lung.

METHODSForty male Sprague-Dawley rats were divided into equal groups for modeling of cirrhosis and HPS. The two groups were assessed by blood gas analysis, standard biochemical tests to measure D-dimer, PT, Fib, CD4 and CD8, and pathological examination of lung tissues.

RESULTSThe HPS rats showed significantly lower PaO2 than the cirrhosis rats (58.20+/-3.19 mmHg vs. 85.00+/-2.53 mmHg, P = 0.000). The HPS rats showed significantly higher levels of D-dimer, Fib and CD8 than the cirrhosis rats (0.39+/-0.09 mg/ml vs. 0.25+/-0.05 mg/ml, P = 0.000; 1.77+/-0.10 g/L vs. and 1.49+/-0.09 g/L, P = 0.010; 32.32+/-4.45/mm3 vs. 20.13+/-6.09/mm3, P = 0.014). The HPS rats showed significantly lower levels of PT, CD4 and CD4/CD8 than the cirrhosis rats (14.86+/-1.04 s vs. 16.23+/-0.75 s, P = 0.036; 20.45+/-3.86/mm3 vs. 26.75+/-5.32/mm3, P = 0.000; 0.64+/-0.09 vs. 1.32+/-0.13, P = 0.000). The lung tissues of the HPS rats showed microthrombosis in pulmonary vessels, which were not observed in lung tissues of the cirrhosis rats.

CONCLUSIONHPS-related differential levels of D-dimer, PT, Fib, CD4, CD8 and CD4/CD8 may represent a biomarker profile suggestive of incidence of thromboembolism in lung.

Animals ; CD4 Antigens ; metabolism ; CD4-CD8 Ratio ; CD8 Antigens ; metabolism ; Disease Models, Animal ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Hepatopulmonary Syndrome ; blood ; Liver Cirrhosis ; blood ; Lung ; pathology ; Male ; Prothrombin Time ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the expression of ET-1 mRNA in the lung of rats with hepatopulmonary syndrome.

METHODSMale Sprague-Dawley rats were divided into four groups: SO, IHPH, PHPH and PCS. Two weeks after production of rat models, all measurements were performed. Arterial blood gas was analyzed. The concentrations of NO and ET-1 in lungs were measured by using radioimmunoassay. In situ hybridization, ET-1 mRNA expressions were detected in lung tissue sections with digoxin-labeled ET-1 oligonucleotide probes. Liver and lung tissues and all the results of in situ hybridization were analyzed by one pathologist. At a magnification of 10 x 40, percent areas of positive stains were detected to indicate the expressions of ET-1 mRNA in the arteries, capillaries and branches.

RESULTSArterial blood gas analysis showed that PaO(2) (mmHg) decreased more significantly in IHPH (73.85 +/- 6.51) rats than in PHPH (97.39 +/- 1.33), PCS (95.23 +/- 2.22) and SO rats (99.05 +/- 0.75). Alveolar-arterial oxygen gradient (A-aG) (mmHg) increased more significantly in IHPH rats (32.99 +/- 6.57) than in PHPH (4.98 +/- 1.69), PCS (6.51 +/- 2.04) and SO rats (3.23 +/- 0.81). Changes of vascular active substance in plasma and lung indicated that the level of lung NO of IHPH (19.78 +/- 5.33) was increased significantly more than that of PHPH (13.21 +/- 3.99) and PCS (13.89 +/- 3.16). These levels in lung homogenate increased more significantly than those SO (8.71 +/- 1.68). The levels of ET-1 in IHPH rats (195.1 +/- 36.2) was significantly lower than in PHPH (234.8 +/- 71.0), PCS (240.4 +/- 66.5) and SO rats (271.8 +/- 40.6). ET-1 mRNA in situ hybridization showed that there was no significant difference in positive expression of ET-1 mRNA in alveolar arteries and small bronchi. The expression of ET-1 mRNA was significantly lower in alveolar capillary endothelia (5.12 +/- 1.27) than in PHPH (7.43 +/- 0.83), PCS (7.07 +/- 0.86) and SO (7.81 +/- 1.98) rats.

CONCLUSIONThe low expressions of ET-1 mRNA in HPS rat alveolar capillary endothelia accompanied by decreased ET-1 levels in lung may play an important role in the mechanism of HPS.

Animals ; Disease Models, Animal ; Endothelin-1 ; biosynthesis ; genetics ; Hepatopulmonary Syndrome ; metabolism ; pathology ; Image Processing, Computer-Assisted ; In Situ Hybridization ; Lung ; metabolism ; pathology ; Male ; Nitrates ; metabolism ; Nitrites ; metabolism ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the protective effects of ofloxacin by reduction of endotoxin on lung in rats with hepatopulmonary syndrome (HPS).

METHODSRat models of HPS were induced by ligating the bile duct to result in the biliary cirrhosis. Thirty male SD rats were randomly divided into three groups with 10 animals in each one: sham operation group (the bile ducts were isolated and 2 ml NS was injected i.p), HPS model group (the bile ducts were ligated and 2 ml NS was injected i.p) and levofloxacin group (the bile ducts were did as the former group and 20 mg/kg ofloxacin injected i.p). After 6 weeks the portal pressure, ratios of dry weight to wet weight of lung (D/W), weight of spleen, plasma levels of endotoxin, MPO active and MDA contents in the lung. Plasma and lavage fluid of lung were examined. The results of the blood-gas analysis, the bacterial culture of blood, bile and ascites and the evaluation of pathologic change of lung be also investigated.

RESULTSIn levofloxacin group, portal pressure [(19.28 +/- 2.3) compare with (17.80 +/- 2.18)cm H2O, P<0.01], D/W [(5.1 +/- 0.7) compare with (4.9 +/- 0.7), P <0.01], plasma endotoxin levels [(59 +/- 6.2) compare with (268 +/- 35.6)ng/L, P<0.01], MPO active [(0.40 +/- 0.10) compare with (0.24 +/- 0.03)U, P<0.01] and MDA [(0.32 +/- 0.05) compare with (0.22 +/- 0.03) micromol/L, P<0.01] contents in the lung were significantly decreased compared with those in HPS group, and the inflammation of lung was also obviously alleviated.

CONCLUSIONReduction of endotoxin can attenuate the injury of lung in HPS rats.

Animals ; Anti-Bacterial Agents ; therapeutic use ; Bronchoalveolar Lavage Fluid ; chemistry ; Endotoxins ; blood ; Hepatopulmonary Syndrome ; blood ; drug therapy ; Levofloxacin ; Lung ; drug effects ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Ofloxacin ; therapeutic use ; Portal Pressure ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the correlation between radiologic vascular dilatation and serum nitrite concentration and eNOS expression in the endothelial cell and pneumocyte in a rabbit model of hepatopulmonary syndrome induced by common bile duct ligation (CBDL). MATERIALS AND METHODS: Thin-section CT scans of the lung and pulmonary angiography were obtained 3 weeks after CBDL (n=6), or a sham operation (n=4), and intrapulmonary vasodilatation was assessed. The diameter and tortuosity of peripheral vessels in the right lower lobe by thin-section CT and angiography at the same level of the right lower lobe in all subjects were correlated to serum nitrite concentration and eNOS (endothelial nitric oxide synthase) expression as determined by immunostaining. RESULTS: The diameters of pulmonary vessels on thin-section CT were well correlated with nitrite concentrations in serum (r = 0.92, p < 0.001). Dilated pulmonary vessels were significantly correlated with an increased eNOS expression (r = 0.94, p < 0.0001), and the severity of pulmonary vessel tortuosity was found to be well correlated with serum nitrite concentration (r = 0.90, p < 0.001). CONCLUSION: The peripheral pulmonary vasculature in hepatopulmonary syndrome induced by CBLD was dilated on thin-section CT and on angiographs. Our findings suggest that peripheral pulmonary vascular dilatations are correlated with serum nitrite concentrations and pulmonary eNOS expression.
Angiography ; Animals ; Common Bile Duct/injuries ; Dilatation, Pathologic/radiography ; Disease Models, Animal ; Endothelium, Vascular/metabolism ; Hepatopulmonary Syndrome/etiology/*metabolism ; Ligation ; Lung/*blood supply/metabolism/*radiography ; Nitric-Oxide Synthase/*metabolism ; Nitrites/*blood ; Pulmonary Artery/radiography ; Rabbits ; Research Support, Non-U.S. Gov't ; Tomography, X-Ray Computed/methods

OBJECTIVETo explore the mechanism of tanshinol on alleviate the inflammatory injury of lung tissue in rat hepatopulmonary syndrome (HPS).

METHODSSD rats were randomly divided into normal control group (n = 8), hepatopulmonary syndrome (HPS) group (n = 11) and tanshinol intervention group (n = 9). HE staining was used to observe the histopathology changes of pulmonary and hepatic tissues, and to count the number of macrophages in lung tissues. The activity of alanine transferase (ALT) and concentrations of endotoxin, tumor necrosis factor-a (TNF-alpha) and homocystein (Hcy) in plasma were detected. The concentrations of TNF-alpha, nitric oxide (NO) and malondialdehyde (MDA) and the activity of inducible nitric oxide synthase (iNOS) in the lung tissues were measured, respectively.

RESULTSThickened alveolar septum and increased macrophages were observed in lungs in HPS rat. After administered with tanshinol, the pulmonary pathological changes were alleviated and the number of macrophages in lung tissue was decreased compared with HPS group. The activity of ALT and the concentrations of endotoxin, TNF-alpha and Hcy in plasma ,and TNF-alpha, iNOS, NO and MDA in lung tissue in HPS group were higher than those of normal control group; meanwhile, those tanshinol group were less those that of HPS group.

CONCLUSIONTanshinol may play an important role in delaying the development of HPS through protecting liver or directly antagonizing the effect of intestinal endotoxemia so as to alleviate the inflammatory reaction in lung tissue.

Alanine Transaminase ; metabolism ; Animals ; Caffeic Acids ; pharmacology ; Disease Models, Animal ; Endotoxins ; blood ; Hepatopulmonary Syndrome ; drug therapy ; pathology ; Homocysteine ; blood ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood