AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction,and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic ra...AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction,and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic rats. METHODS: Male Wister rats were fed with a diet containing maize flour,lard,cholesterol,and alcohol and injected subcutaneously with CCl4 oil solution every two days for 8 wk to induce typical cirrhosis and development of HPS. The animals were also given a nitric oxide (NO) production inhibitor,Nω-nitro-L-arginine methyl ester (L-NAME) intraperitoneally,and an iNOS inhibitor,aminoguanidine hydrochloride (AG) via gavage daily from the end of the 4th wk to the end of the 6th or 8th wk,or a HO-1 inhibitor,zinc protoporphyrin (ZnPP) intraperitoneally 12 h prior to killing. Blood,liver and lung tissues were sampled. RESULTS: Histological deterioration of the lung paralleled to that of the liver in the cirrhotic rats. The number of pulmonary capillaries was progressively increased from 6.1 ± 1.1 (count/filed) at the 4th wk to 14.5 ± 2.4 (count/filed) at the 8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated with increased blood levels of lipopolysaccharide (LPS)(0.31 ± 0.08 EU/mL vs control 0.09 ± 0.03 EU/mL),alanine transferase (ALT,219.1 ± 17.4 U/L vs control 5.9 ± 2.2 U/L) and portal vein pressure. Compared with normal control animals,the number of total cells in bronchoalveolar lavage fluid (BALF) of the cirrhotic rats at the 8th wk was not changed,but the number of macrophages and the ratio of macrophages to total cells were increased by nearly 2-fold,protein expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) started to increase significantly at the 4th wk,and reached its peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression appeared to be quicker than that of eNOS. NO2-/NO3-was also increased,which was correlated to the increase of iNOS (r = 0.7699,P < 0.0001) and eNOS (r = 0.5829,P < 0.002展开更多
基金Supported by the Awards to University Academic Leaders Granted by the Government of Shanxi Province of China to Hui-Ying Zhang and partially by the US National Institute of Health, NIAAA, Grant R01 AA014428 to Cheng Ji
文摘AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction,and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic rats. METHODS: Male Wister rats were fed with a diet containing maize flour,lard,cholesterol,and alcohol and injected subcutaneously with CCl4 oil solution every two days for 8 wk to induce typical cirrhosis and development of HPS. The animals were also given a nitric oxide (NO) production inhibitor,Nω-nitro-L-arginine methyl ester (L-NAME) intraperitoneally,and an iNOS inhibitor,aminoguanidine hydrochloride (AG) via gavage daily from the end of the 4th wk to the end of the 6th or 8th wk,or a HO-1 inhibitor,zinc protoporphyrin (ZnPP) intraperitoneally 12 h prior to killing. Blood,liver and lung tissues were sampled. RESULTS: Histological deterioration of the lung paralleled to that of the liver in the cirrhotic rats. The number of pulmonary capillaries was progressively increased from 6.1 ± 1.1 (count/filed) at the 4th wk to 14.5 ± 2.4 (count/filed) at the 8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated with increased blood levels of lipopolysaccharide (LPS)(0.31 ± 0.08 EU/mL vs control 0.09 ± 0.03 EU/mL),alanine transferase (ALT,219.1 ± 17.4 U/L vs control 5.9 ± 2.2 U/L) and portal vein pressure. Compared with normal control animals,the number of total cells in bronchoalveolar lavage fluid (BALF) of the cirrhotic rats at the 8th wk was not changed,but the number of macrophages and the ratio of macrophages to total cells were increased by nearly 2-fold,protein expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) started to increase significantly at the 4th wk,and reached its peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression appeared to be quicker than that of eNOS. NO2-/NO3-was also increased,which was correlated to the increase of iNOS (r = 0.7699,P < 0.0001) and eNOS (r = 0.5829,P < 0.002
