ABSTRACT
Aim To observe the effect of Salvianolic-aid B ( Sal B ) on the progression of hepatic fibrosis-carcinoma in mice induced by diethylnitrosamine ( DEN ) and investigate the mechanism of Sal B in-volved in the shift between pSmad 3 C/p21-mediated tumor suppressive signaling and pSmad 3L/PAI-1/c-Myc-mediated pro-fibrogenic/oncogenic signaling . Methods A total of 100 male Kunming mice were randomly grouped , DEN-induced hepatic fibrosis-car-cinoma model of mice was established , which was in-tragastrically treated by Sal B with two dosages ( 15 , 30 mg · kg -1 ) and colchicine with one dosage ( 0.2 mg· kg -1 ) , respectively.The mice were sacrificed at 12th week or 16th week after the start of DEN adminis-tration.Pathological changes of livers in each group were assessed by liver biopsy , hematoxylin-eosin ( HE ) staining and Van Gieson ( VG ) staining .The protein expressions of pSmad3C, pSmad3L, p21, plas-minogen activator inhibitor-1 ( PAI-1 ) and c-Myc in liver tissues were assayed by Western blot .Results In the normal control group , the surface of mouse liver was smooth and soft , and the structure of the hepatic lobule was intact.In the DEN alone group, at 12th week, the surface of mouse liver was rough and hard , the hepatic lobule was encysted or separated by colla-gen bundles, and pseudolobules emerged.At 16th week, the surface of mouse liver in the DEN alone group was rough with some nodules. HE and VG staining showed that the hepatocytes of nodules with obvious atypia and hyperchromatic nuclei were veri-fied.However, these pathological changes were evi-dently improved in Sal B treatment groups compared with the DEN group , which was proved by reductive cirrhotic nodules and alleviative fibrosis at 12th week, and decreasing cancerous nodes and ameliorative dif-ferentiation via Sal B treatment at 16th week.Western blot results showed that the protein expression of pS-mad3C, pSmad3L, PAI-1 were less, and c-Myc ex-pression was scarcely found in normal group; in DEN alone group, at 12th week, the protein expression of pSmad3C had no significant change , while the protein levels of pSmad3L, PAI-1, p21 were up-regulated, and at 16th week, the protein expressions of pS-mad3C, pSmad3L, p21, PAI-1 and c-Myc increased. In Sal B treatment group, the expressions of p21 and pSmad3C increased significantly , pSmad3L and PAI-1 protein levels markedly decreased at 12th week, the expression of pSmad3C increased obviously , p21 was almost unchanged , and the expression of pSmad 3L, PAI-1 and c-Myc were significantly reduced at 16th week .Conclusions Sal B could delay the progression of hepatic fibrosis-carcinoma in mice induced by DEN , and the mechanism may involve mediating the shift of pSmad3C/p21 and pSmad3L/PAI-1/c-Myc signaling.
ABSTRACT
Objective To investigate the predictive value of serum aldosterone and Plasminogen activator inhibitor-1 ( PAI-1 ) levels to the severity of coronary artery lesions and the recent prognosis in acute coronary syndrome (ACS) patients underwent percutaneous coronary intervention(PCI). Methods The study included 160 consecutive patients admitted. All the patients received coronary angiography and were divided into two groups:control group and ACS group. The patients' blood samples were abtained at the root of aortic artery to measure the serum aldosterone and PAI-1 levels. We analyzed their relationship with the severity of coronary artery lesions. The patients were also divided into three groups( high-score group, moderate-score group,low-score group)according to Gensini accumulated points,we analyzed the difference of aldosterone and PAI-1 levels in three groups. The predictive values of aldosterone and PAI-1 to the recent pronosis of ACS patients underwent PCIwere assessed. Results ( 1 )The patients' serum aldosteeone and PAI-1 levels in ACS group were significantly higher than control group( all P <0. 05 ) ;(2)The aldosterone and PAI-1 levels in high-score group were higher than moderate-score group, and moderate-score group was higher than low-score group. (3)The serum aldosterone level in ACS patients was positively correlated with the PAI-1 level ( r = 0.213, all P < 0. 05 ). ( 4 ) Multiple factor Logistic regression analysis indicated that aldosterone, PAI-1 levels were srtong independent predictors for the recent prognosis of ACS patients underwent PCI. Conclusion The aldosterone ,PAI-1 levels in ACS patients were correlated with the severity of coronary artery lesions. Both of them were strong predictors for the recent prognosis of ACS patients underwent PCI.