Objective To investigate whether protease inhibitor (ulinastatin, UTI) can protect liver from ischemiareperfusion injury in hepatocellular carcinoma (HCC) patients undergoing hepatectomy after hepatic inflow occlusion. Methods A prospective randomized control study was designed. Thirtyone HCC patients undergoing hepatectomy after hepatic inflow blood occlusion were randomly divided into the following two groups. UTI group (n=16)， 1×105 units of ulinastatin was given intravenously in operation, then the dosage was continuously used twice a day up to 5 days postoperatively. Control group (n=15), the patients received other liver protective drugs. Liver function, plasma C-reactive protein (CRP) and cortisol level were compared between these two groups. Results The postoperative liver function of the UTI group was significantly improved compared with the control group. For example, on the third postoperative day the aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin level in the UTI group were significantly lower than those in the control group, respectively (P＜0.05). On the first postoperative day, the plasma CRP concentration in the UTI group was significantly lower than that in the control group(P＜0.01). The plasma cortisol level in the control group markedly increased compared with the level before operation(P=0.046). However, there was no significant difference in the UTI group between before and after operation. Conclusion Ulinastatin can effectively protect liver from ischemia/reperfusion injury in HCC patients undergoing hepatectomy performed after hepatic inflow occlusion. Also, it can relieve the surgical stress for patients.
Objective To explore the effect of Tie-2 small interference RNA (siRNA) treatment in human hepatoma transplanted subcutaneously in nude mice. Methods Tumor cells were implanted in the hind flank of male nude mice of 6 weeks. Tumor-bearing mice were divided into two groups （gene therapy group and control group） and injected intra-tumorally with Tie-2-siRNA/Lipofectamine and saline/Lipofectamine respectively. The tumor volume and weight, serum AFP and microvessel density (MVD) and the histological change of the tumor were tested after gene therapy. Results The growth inhibitory rates in gene therapy group were 26.94%， 53.01% and 68.91% on day 4， 7 and 10 after gene therapy respectively. The tumor volumes of gene therapy group (118.47, 111.57 and 104.59 mm3) were smaller than those of the control group (162.17, 237.46 and 336.41 mm3) respectively (P＜0.01), and the weight of tumor in gene therapy group was lighter than that of the control group 〔(0.89±0.09) g vs (1.24±0.03), P＜0.01〕. The AFP value in gene therapy group was obviously lower than that of the control group 〔(107.66±24.13) ng/ml vs (266.08±50.96) ng/ml, P＜0.01〕. There was significant diference of MVD between the gene therapy group (34.63±4.07) and the control group (81.01±9.44) with the method of immunohistochemitry (P＜0.01). Histopathology in the control group showed that the tumor volumes were bigger, and a high atypic of tumor cells were seen. The main pathological changes in tumor tissue of gene therapy group were necrosis, there were massive necrosis. The apoptosis cells were seen in the both of necrosis and non-necrosis areas in only 2 mice of gene therapy group. Conclusion Tie-2-siRNA inhibits the tumor growth and tumor angiogenesis， and is a possible new approach for liver neoplasm gene therapy.
Objective To investigate the extent of hepatic ischemia reperfusion (HIR) injury in rat cirrhotic liver under different ischemic time，and find the time limit under which the rat with cirrhotic liver could tolerate. Methods At first，the cirrhosis of the rat were induced by carbon tetrachloride（CCl4）injected subcutaneously. Then these rats were randomly divided into four groups. Group A(n=6) was made by sham operation, group B, C, D(n=16) were respectively given 20, 30, 40min hepatic warm ischemia. The 7day survival rate, AST, ALT, TNF and liver, pulmonary pathology were observed. Results The 7-day survival rate was decreased with the increase of hepatic ischemic time. The survival rate of group B, C, D were respectively 100%, 60%, 40%. Between group C, D and group B there were significant differences（P＜0.05）. The level of AST and ALT in group D were （2 448.4±942.3）u/L and （1 189.0±403.4）u/L respectively, and those in group C were （2 185.1±1 732.9）u/L and （1 183.5±707.2）u/L respectively, which were higher than those in group B and A significantly（P＜0.01）. The level of TNF was increased significantly 4hr after reperfusion, as compared with that before operation 〔(0.177±0.139）u/ml〕, P＜0.01. TNF of group B, C, D were （0.399±0.216）u/ml, （0.671±0.351）u/ml and （0.789±0.371）u/ml respectively. At the same time the level of TNF in group C, D was higher than that in group B, A significantly（P＜0.01）. Liver and lung pathology showed increased damage with increasing ischemia. Conclusion Hepatic injury is induced by HIR in rats with cirrhotic liver, and its severity increases with the increase of ischemic time. There is a certain hepatic ischemic time between 20min and 30min, which can be tolerated by the rats with cirrhotic liver. TNF may be used as an indicator，showing the degree of HIR injury and foreseeing the result of injury.
