ObjectiveTo investigate the protective effect of SadenosylLmethionine on liver regeneration and liver function in cirrhotic rats after hepatectomy. MethodsCirrhosis was successfully induced by injection of 40% CCl4.Then,partial hepatectomy (about 30%) was performed in all rats. Cirrhotic rats were divided into 3 groups,namely,cirrhotic group (normal saline 5 ml/d,for 15 postoperative days，n=20),treatment group 1 〔S adenosylLmethionine 10 mg/(kg·d),for 15 postoperative days,n=16〕 and treatment group 2 〔SadenosylL methionine 20 mg/(kg·d),15 postoperative days,n=16〕,and normal control group was also established. Animals were sacrificed at the 15th postoperative day and 30th postoperative day to take samples for detection of liver function (Alb,ALT,TB,TBA) and serum TNFα.Liver tissues were also observed under light microscope and electron microscope. ResultsIn two treatment groups,at the time point (15 postoperative days or 30 postoperative days),concentrations of ALT,TB,TBA,Alb and TNFα were decreased significantly as compared with cirrhotic group (P ＜0.01),and concentration of Alb was increased significantly (P＜0.01).In contrast, there were no obvious difference in the same time point of different dosetreatment groups (Pgt;0.05),but the decrease of ALT,TB,TBA,TNFα and the increase of Alb were more significant at the second time point (30th postoperative day) than the first time point (15th postoperative day) when treated with same dose (P＜0.01).At the same time,concentration between TNF α and ALT,TB,TBA showed a positive correlation (P＜0.01),and the concentration between TNFα and Alb showed a negative correlation (P＜0.01).In addition, the histopathology showed SadenosylLmethionine had effects of protecting liver function and enhancing liver regeneration. ConclusionThe study suggests that SadenosylL methionine has the efficacy of enhancing liver regeneration and improving liver function.
ObjectiveTo investigate the relationship between hormone and liver regeneration.MethodsThe related literatures in recent years were collected and reviewed.ResultsHormone was related to liver regeneration significantly and participated the process of liver regeneration. It had a promotive or inhibitive role in liver regeneration.ConclusionHormone is one of the important factors in the regulation of liver regeneration.
Objective To study the effect of recombinant growth hormone (rhGH) on improvement of liver function and liver regeneration in animal and patients after hepatectomy. Methods The liver cirrhosis model of SD species mouse was set up, then the mouse were randomly divided into experiment group and control group, then 30%-40% liver of all the models were resected, rhGH was used by hypodermic injection (0.2-0.4ml/100g) in experimental group, and the equal dose of N.S. were given in control group every day. Then liver function, arterial blood ketone body ratio(AKBR), and the regenerated liver/body weight ratio (RL/W) were determined, histopathology of the cirrhosis with microscope and electron microscope and the mitotic index (MI) of liver cell on 7, 14 and 28th day after operation were observed. Clinically,39 hepatectomized patients were randomly divided into experiment group and control group, liver function, PA， Glu, RI and AKBR were measured preoperatively and on 1, 7,14th day after operation. Postoperative clinical course were also compared between the two groups. Results In the animal experiment group, as compared with the control group, AKBR was obviously higher (P＜0.01), seruim level of total protein and PA were increased faster (P＜0.05), and RL/W was higher. The mitotic index of liver cell was increased faster on 14th day, the numbers of regenerated liver cell with double nucleus and rough endoplasmic reticulum were higher in 14 and 28th day. In the clinical experiment group, as compared with the control group, serum total bilirubin, alanine aminotransferase and aspartate aminotransferase were lower on 7 and 14th postoperative day (P＜0.05). Serum albumin, PA, Glu, RI and AKBR were higher on 7, 14th postoperative day (P＜0.05). Conclusion Both experimental and clinical study show that the rhGH can promote liver regeneration and improve liver function after hepatectomy.
In order to observe the effect of hepatocyte growth promoting factor (pHGF) on liver regeneration of rat with cirrhosis after hepatectomy, IBAS Ⅱ auto image analysis technology was used to measure the variety of DNA ploid rate of hepatocytes and OPTDM of enzymes by liver histochemistry after hepatectomy; serum levels of the glutamicpyruvic transaminase (SGPT) and indocyanine green retention rate in 15 minute (ICG15) were tested to measure the function of the remanent liver. The results revealed that tetraploid hepatocytes lowered greatly and diploid, quintploid and ＞quintploid hepatocytes increased apparently in group A. OPTDM of enzymes by liver histochemistry showed no significant difference at the first day after operation in each group (Ｐ＞0.05); SDH and LDH of group A were significantly higher than those of group B and AkP, AcP were significantly lower at the second or fifth day after hepatectomy. Serum tests showed that SGPT, ICG15 of group A decreased apparently at the fifth day after operation. The results demonstrate that pHGF not only stimulates the regeneration of the remanent liver but also accelerates the functional mature of the regenerative hepatocytes and the functional recovery of the remanent liver after resection of cirrhotic liver of rats.
Objective To analyze and summarize the research progression of phenotypic markers of hepatic sinusoidal endothelial cell （HSEC） and its role in the development and progression of the liver diseases. Methods Databases such as PubMed， Wanfang， CNKI， etc were retrieved for the latest articles on research advance in HSEC using “hepatic sinus endothelial cell”， “liver regeneration”， and “liver disease” as key words. All of the publications about studies on relation between HSEC and liver disease were reviewed and summarized. Results HSEC with specific cytoarchitectures and phenotypic markers was initially received “the message of damage” in the process of liver regeneration， hepatic immunological tolerance， hepatic fibrosis， and liver damage. Additionally， HSEC as the first barrier not only enabled liver to be protected but also was regarded as the first alternation of liver damage. Therefore， HSEC played a great important role in the process of the onset and progression of the liver disease. Conclusions The function of HSEC is complex. How do play a role and its the mechanism is unclarified， it is needed to be further studied.
Objective To investigate the expressions of transforming growth factor (TGF) -α and -β1 after 90% portal branch ligation (PBL) in rats. Methods Ninety-six SD rats were randomly divided into sham operation group and portal vein branches ligation group. The weight of both ligated and unligated lobes of liver were measured on 0.5, 1, 3, 5, 7, 14, 21, and 28 d after operation. The morphological changes of the unligated liver lobes were observed by microscope. The expressions of proliferating cell nuclear antigen (PCNA), TGF-α, and TGF-β1 of the unligated liver lobes were detected by immunohistochemistry. Results After the ligation of 90% portal vein branches, hepatic lobe at the ligated side diminished progressively after ligation, whereas the lobes of the unligated side underwent compensatory regeneration. The ratio of unligated lobes weight to the whole liver increased slowly within 1 d, speeded up significantly during 1-5 d period, increased slowly on 5 d, and reached plateau phase on 7 d after operation. The expressions of PCNA protein markedly increased within 0.5-3 d (Plt;0.01), which reached the peak on 5 d and decreased slightly on 7 d after operation, but still higher than sham operation group level, and then gradually returned to the level of sham operation group lately. The expressions of TGF-α and TGF-β1 in the unligated liver lobes markedly increased on 0.5 d, and reached the peak on 3 d and 1 d respectively， and then gradually returned to the level of sham operation group in 7-28 d after operation. Conclusion Ligation of 90% portal branches can induce active regeneration of unligated liver lobes in rats, whose initiation and proliferation are involved in the expressions of TGF-α and TGF-β1 protein.
Objective To review the regulation of liver regeneration factors. Methods The literatures about liver regeneration related regulators in recent years were reviewed. Results With further advancement of researches on regulators of liver regeneration in recent years, there were more therapies for treatment of liver-related diseases. Regulators play important roles in the process of liver regeneration, as one of which, cell growth factor plays an essential role in liver cell proliferation, such as the proper expression of TNF-α and IL-6 promoting liver cell proliferation, HGF, TGF-α, EGF, ALR, FS, and others motivating liver cell proliferation, while TGF-β and IL-1 physically terminating liver cell proliferation. Conclusion By strengthening the studies on liver regeneration regulators, new methods may appear for treating liver-related diseases.
ObjectiveTo evaluate the effect of heparin binding epidermal growth factor-like growth factor (HB-EGF) on liver regeneration after partial orthotopic liver transplantation. MethodsFourty SD rats were used to establish the model of partial orthotopic liver transplantation with ameliorated two-cuff technique. Then all the rats were divided into 2 groups: experiment group and control group. Twenty rats of experiment group were administered 500 μg/kg HBEGF via vena caudalis immediately after operation twice a day, while the same volume of saline was administered to the rats in control group. Five rats in each group were selected randomly and killed at the 6th hour, day 2, 4 and 7 after operation, respectively. The serum levels of albumin (Alb) and alanine aminotransferase (ALT) in the blood sample were detected. Every liver was removed and weighed. The expression of Ki67 was detected by using immunohistochemistry assay. The regeneration activity of hepatocytes was evaluated by flow cytometry. ResultsThe wet weights of liver in experiment group were all significantly higher than that in control group at the 6th hour, day 2 and 4 after transplantation (P＜0.05). The serum levels of ALT were significantly lower in experiment group than those in control group at the 6th hour, day 2， 4, 7 after operation (P＜0.05), while the levels of Alb were significantly higher on day 4 and 7. The proliferating index and Ki-67 labeling index of graft in experiment group were higher than those in control group on day 2 and 4 after transplantation （2 d: P＜0.01; 4 d: P＜0.05）. ConclusionHBEGF could promote the regeneration of rat hepatocytes after partial liver transplantation.
Objective To examine the effect of zinc finger protein A20 on regeneration of small-for-sized liver allograft, graft rejection and recipient rat survival time. Methods Small-for-sized liver transplantation with 30% partial liver allograft was performed by using a b-rejection combination rat model of DA (RT1a) to Lewis (RT1l) rats. The rats were grouped into rAdEasy-A20 treatment group （A20 group）, the control empty Ad vector rAdEasy treatment group (rAdEasy group) and PS control treatment group (PS group). Ex vivo gene transfer in donor liver graft was performed through portal vein infusion. Animals were assessed for survival days, expression of A20 in liver graft, liver graft regeneration, hepatocyte apoptosis, graft rejection, NF-κB activation and ICAM-1 mRNA expression in liver graft sinusoidal endothelial cells (LSECs), number of liver graft infiltrating mononuclear cells (LIMCs) and the subproportion of NK/NKT cells, and serum IFN-γ level. Results Survival day of A20 group rats was prominently longer than that of PS group rats and rAdEasy group rats (P=0.001 8), whereas survival day of rAdEasy group rats was remarkably shorter than that of PS group rats (P=0.001 8). Regeneration of the small-for-sized liver allograft was markedly augmented by A20, BrdU labelling index of hepatocyte on postoperative day 4 was significantly increased in the A20 group compared with the PS group and rAdEasy group (P＜0.01). Hepatocyte apoptosis on postoperative day 4 was significantly inhibited by A20 (P＜0.01). On postoperative day 4, histologic examination revealed a mild rejection in the A20 group but a more severe rejection in the PS and rAdEasy groups. NF-κB activity and ICAM-1 mRNA expression in LSECs on postoperative day 1 were notably suppressed by A20 overexpression. Flow cytometry analysis showed a marked downregulation of LIMCs number by A20, including more prominent decrease in the subproportion of NK/NKT cells on postoperative day 1 and 4, respectively (P＜0.05). Serum IFN-γ level on postoperative day 4 was also significantly suppressed by A20 overexpression (P＜0.05). Conclusion These data suggest that A20 could effectively promote small-for-sized liver allograft regeneration, suppresses rejection and prolong survival days of recipient rats. These effects of A20 could be related to an inhibition of LSECs activation, suppression of infiltration of LIMCs and the subpopulations such as NK cells and NKT cells into liver graft, and inhibition of hepatocyte apoptosis.
【Abstract】 Objective To study liver regeneration of the non-ligated liver lobes following portal branch ligation (PBL). Methods Sixty male Wistar rats were randomly divided into PBL group and sham operation (SO) group. Under ether anesthesia, the rats were subjected to PBL and sham operation, respectively. The animals were sacrificed on the 1st, 2nd, 3rd, 7th and 14th day respectively. The blood sample was collected from heart and the livers were harvested to determine serum alanine aminotransferase (ALT) levels and total liver weight, respectively. The hepatic histopathology was studied through light microscopy. The number of liver cell nuclear mitosis index was counted. The number of proliferative cell nuclear antigen (PCNA) index was counted by immunohistochemistry. The hepatic ultrastructural changes were studied under electron microscope. Results ①Elevated serum ALT level was observed in the first postoperative day in PBL group compared with SO group (P＜0.01)， but began to recover in the second day. ②No significant total liver weight change in PBL group and SO group were found. ③Liver cell nuclear mitosis index and PCNA index were markedly increased in PBL group compared with SO group in day 1-3 postoperative day (P＜0.01). It reached the peak in the second day and decreased slightly in the 3rd day, but still higher than SO group, then gradually return to normal lately. Conclusion The ligation of left portal branch can induce active regeneration of hepatic cell of non-ligated liver lobes in rats. The regeneration of non-ligated liver lobes may restore previous total liver weight. The ligation of 75% portal branch does not affect liver function and may be safely performed. The portal branch ligation in rats may be used as an animal model in study of liver regeneration.