Objective To study the relation between changes of the hepatic energy metabolism and allograft viability in early phase after orthotopic liver transplantation, arterial blood ketone body ratio (AKBR) was measured in pre- intra and post-operative phase. Methods The monkeys were divided into two groups in accordance with survived times. A group (>24h), 5 monkeys survived 29—168 postoperative hours; B group (<24h), 9 monkeys survived only 5—22 hours. Results AKBR in all models immediately decreased to extraordinarily low state in anhepatic-phase (versus preanhepatic phase, P<0.01), and A group recovered rapidly to the normal levels, and maintained continuously for 12 postoperative hours above the level of 0.7. In contrast in B group, AKBR decreased below 0.7 rapidly and failed to restore to the normal level. Within 12 hours postoperatively, in B group, AKBR was lower than 0.4. Conclusion AKBR is a sensitve indicator to the allograft viability in the early phase after hepatic transplantation.
Objective To study the effect of Kupffer cell on the liver ischemia/reperfusion injury.Methods The literature in recent years on the liver ischemia/reperfusin injury were reviewed.Results The activated kupffer cell can generate and release a variety of soluble toxic mediators, affect the liver microcirculation directly or indirectly. Conclusion Kupffer cell have important effect on liver ischemia/reperfusion injury.
Objective To assess value and limitations of non-invasive methods in assessing liver fibrosis.Methods By summarized current situation and advancement of serum fibrotic markers, ultrasound, CT and MRI in assessing liver fibrosis, we investigated their value and limitations. Results In addition to diagnosis, non-invasive methods of assessing liver fibrosis assess severity of liver fibrosis. For liver fibrosis, however, non-invasive methods can not monitor effectively reaction to therapy and progression. Conclusion Non-invasive methods play important roles in diagnosis and assessing severity of liver fibrosis, and reduce the need of liver biopsy.
【Abstract】ObjectiveTo construct a recombinant eukaryotic expression vector for human endostatin in order to study the inhibitory effect of liposome-mediated endostatin gene on the growth of human liver carcinoma in nude mice. MethodsHuman endostatin cDNA including IL-2 secreting peptide was cloned into eukaryotic expression plasmid pcDNA3.0 to construct recombinant plasmid pCD-sEndo. pCD-sEndo plasmid was transferred into hepatocarcinoma cell line SMMC-7721 mediated by liposome Dosper, the expression and secretion of endostatin gene was detected by RTPCR and Western blot analysis. The suspension of SMMC-7721 cells was injected subcutaneously at the back of 32 nude mice to establish the model of human liver carcinoma. The mice were divided into 4 groups randomly, and injected with Dosper+pCD-sEndo, Dosper+pcDNA3.0, Dosper and physiological brine separately. Tumor volume was measured by stages. The mice were executed after the drug had been given for 1 week, then the microvessel density (MVD) of the tumor tissue was detected with immunohistochemical method and apoptotic index of tumor cells was measured by TUNEL-stain. ResultsThe eukaryotic expression vector pCD-sEndo was successfully constructed and was confirmed by enzyme digestion and sequence analysis. Expression of endostatin gene was detected in transfected SMMS-7721 cells by RTPCR in vitro, and endostatin protein was also detected in the supernatant of transfected SMMS-7721 cells by Western blot. In vivo study, the growth of human liver carcinoma was inhibited in the group injected with endostatin gene: the average volume of tumor in this group was significantly smaller than that in other groups (P<0.05); the average MVD in this group was 6.2±2.5, significantly less than that in the group injected with physiological brine (32.8±6.4), Dosper (27.8±6.4), or Dosper+pcDNA3.0 (25.5±5.5), P<0.05. The average apoptotic index of tumor cells in treatment group, brine group, Dosper group and Desper+pcDNA3.0 group was 24.5±7.3, 7.6±2.5, 9.5±3.0 and 11.2±3.6 respectively, it was evidently higher in the treatment group than in the latter three groups. ConclusionHuman endostatin mediated by cation liposome could decrease the microvessel number of implanted human hepatocarcinoma in nude mice. It could also accelerate apoptosis of tumor cells and inhibit growth of tumor.
Objective To observe the effects of Thymosin α1 (Tα1) on acute rejection after liver transplantation and immune function of T cells. Methods Twenty recipients of liver transplantation due to primary hepatic carcinoma were divided into two groups: Tα1 group (n=10) and control group (n=10). Tα1 group received subcutaneous injection of Tα1 1.6 mg on the first day after liver transplantation and then twice a week for at least one month. Both Tα1 group and control group took same immunodepressants. Core biopsies were carried to compare the incidence rate of acute rejection between Tα1 group and control group. Peripheral T cellular immune function in these two groups was detected on 1 d before, 1 week, 2 weeks and 1 month after transplantation. Results There was not significant difference of incidence rate of acute rejection between Tα1 group and control group (Pgt;0.05). In the Tα1 group, CD4+, CD8+ lymphocyte cell counts and the CD4+/CD8+ ratio were significantly higher than those in the control group in 2 weeks and 1 month after transplantation (P<0.05). Conclusion Use of Tα1 in recipients who also takes rountine immunosuppressants dose not increase the risk of occurring acute rejection after liver transplantation. Tα1 can significantly increase CD4+, CD8+ counts and CD4+/CD8+ ratio, which shows that Tα1 may improve recipients’ cellular immune function.
Objective To review the advances of livingrelated liver transplantation for children. MethodsOn the basis of the data in Kyoto university, the center of livingrelated liver transplantation in the world, the current situation of livingrelated liver transplantation for children were investigated. ResultsEighty percent of patients who underwent the livingrelated liver transplantation were children with cholestatic liver disease. From the data of 462 cases, the patients’survival rate for 1, 3 and 5 years after livingrelated liver transplantation (79.8%, 77.0% and 77.0% respectively) preceded the survival rate of 129 patients who underwent the whole liver transplantation (76.0%, 70.0% and 65.0% respectively). To the livingrelated liver transplantation, the survival rate was higher for patients who underwent selective operation (85.0%) than emergency surgery (67.0%). The principal causes of death were rejection and infection. Furthermore, a partial orthotopic liver transplantation and livingrelated liver replantation were performed for children. Conclusion Strict indication, optimal health status and perfect postoperative management are the keys to keep patients longterm healthy survival. The curative effect of livingrelated liver transplantation precedes the whole liver transplantation. For children, livingrelated liver transplantation is better than for adults.
Objective To investigate the change of immunologic gene expression in cases of colorectal cancer with liver metastasis. Methods The total RNAs were extracted from tumor tissues of original lesions in 16 patients with colorectal cancer, DNA microarray was used to examine the change of immunologic gene expression in colorectal cancer patients with or without liver metastasis. Results Compared with samples without liver metastases, the expressions of 11 immunologic genes obviously down-regulated in the tumor tissues of colorectal cancer patients with liver metastasis, including:carboxypeptidase D;Fc fragment of IgE, high affinityⅠreceptor for gamma polypeptide;Fc fragment of IgG, low affinityⅢa receptor (CD16a);free fatty acid receptor 2;interleukin 2 receptor gamma;protein tyrosine phosphatase receptor type C;complement factor B;major histocompatibility complex, classⅡ, DM alpha;major histocompatibility complex, classⅡ, DM beta;major histocompatibility complex, classⅡ, DQ alpha 1;granzyme B. The functions involved the growth and activation of immunologic cell, signal transduction, cell apoptotic, cell factors, receptors, complement, apoptotic, and immunogenicity of tumor cell. Conclusions Down-regulation of a various of immunologic gene expression in colorectal cancer patients with liver metastasis inhibits the function of immunology, and tumor cells escaped the destruction of immunology system results in metastasis.
Objective To explore the cause, diagnosis, and treatment methods of portal vein thrombosis (PVT) after splenectomy. Methods The clinical data of 29 patients who were got splenectomy because of portal hypertension or traumatic splenic rupture from August 2002 to August 2008 in our hospital were analyzed retrospectively. Results Tweenty-seven patients with PVT were treated successfully, whose thrombi were absorbed completely or partially. One case died of peritonitis,septic shock,and multiple organ failure. One case died of hematemesis, hepatic coma,and multiple organ failure. Tweenty-four patients were followed up, the follow-up time was 0.5 to 3 years, the average was 2 years. Two cases died of massive hemorrhage, 1 case died of hepatic encephalopathy,and 1 case died of liver failure. Two cases occurred deep venous thrombosis in one year after treatment, and the remaining patients had no recurrence of venous thrombosis. Conclusions PVT have some connection with the raise of blood platelet and the hemodynamic changes of the portal vein system after splenectomy. Standardization of operation, early diagnosis, early line anticoagulant,and antiplatelet adhesion therapy are effective way to prevent and treat PVT.
To quantitatively measure the α1-adrenergic receptors and select the suitable conditions of receptor-ligand binding assay. Radioligand binding analysis was used to measure the concentration of α1-adrenergic receptors, and the measuring conditions were selected, respectively. Under the selected conditions, the α1-adrenergic receptors in lier plasma membranes of 8 nonhepatopathy subjects were measured.Under such suitable conditions as 3H-prazosin concentration 0.1-2.0nmol/L, incubating temperature 37℃, reaction time 20 minutes and seperating free ligand from system with double layer of filter paper, the binding of 3H-prazosin to α1receptors from 8 nonhepatopathy subjects were saturable with a high affinity. The Bmax, Kd, RMC and Hill coefficient were 142.1±14.1 fmol per milligram of protein, 0.2382±0.0548 nM, 739.0±167.6 fmol per gram of liver and 0.90±0.03, respectively.The suitable conditions may be very important for measuring α1-adrenergic receptors in human liver plasma membranes, which should be considered in hepatopathy studies.
ObjectiveTo study the effects of aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS) on the pathological changes of liver tissues and ultrastructural changes of liver cells in rodent model of endotoxic shock. MethodsTwentyfour male Wistar rats were randomly divided into normal control group,lipopolysaccharide (LPS) control group and AG treatment group, each group had 8 rats. Rats were challenged by E.coli LPS to set up the model of endotoxic shock, AG group were treated by aminoguanidine. The pathological and ultrastructural changes of liver tissues and plasma NO contents of three groups were observed and compared. ResultsLight microscopy revealed that many tiny abscesses scattered in liver tissue in LPS group, accompanied by necrosis of liver cells and neutrophils infiltration, while liver injuries of AG group were much slighter than that in LPS group. Electron microscopy revealed that there were dissolved plaques in hepatocyte nuclears, swelling of mitochondria, decreasing in number of mitochondrial ridges, while AG play a protective role to nuclears and mitochondria of hepatocytes. The plasma NO levels of LPS control group were higher than that of normal control group, and plasma NO levels decreased significantly after AG treatment, but still higher than that of normal control group. Conclusion Aminoguanidine selectively inhibits iNOS activity and prevents the overproduction of NO induced by iNOS, thus attenuates the damages of liver structure induced by NO. This method has potential value in clinical application, which deserves more deep research.