Rapamycin improves the survival of epilepsy model cells by blocking phosphorylation of mTOR base on computer simulations and cellular experiments.

PURPOSE: Epilepsy is a chronic brain dysfunction characterized by recurrent epileptic seizures. Rapamycin is a naturally occurring macrolide from Streptomyces hygroscopicus, and rapamycin may provide a protective effect on the nervous system by affecting mTOR. Therefore, we investigated the pharmacologic mechanism of rapamycin treating epilepsy through bioinformatics analysis, cellular experiments and supercomputer simulation. METHODS: Bioinformatics analysis was used to analyze targets of rapamycin treating epilepsy. We established epilepsy cell model by HT22 cells. RT-qPCR, WB and IF were used to verify the effects of rapamycin on mTOR at gene level and protein level. Computer simulations were used to model and evaluate the stability of rapamycin binding to mTOR protein. RESULTS: Bioinformatics indicated mTOR played an essential role in signaling pathways of cell growth and cell metabolism. Cellular experiments showed that rapamycin could promote cell survival, and rapamycin did not have an effect on mRNA expression of mTOR. However, rapamycin was able to significantly inhibit the phosphorylation of mTOR at protein level. Computer simulations indicated that rapamycin was involved in the treatment of epilepsy through regulating phosphorylation of mTOR at protein level. CONCLUSION: We found that rapamycin was capable of promoting the survival of epilepsy cells by inhibiting the phosphorylation of mTOR at protein level, and rapamycin did not have an effect on mRNA expression of mTOR. In addition to the traditional study that rapamycin affects mTORC1 complex by acting on FKBP12, this study found rapamycin could also directly block the phosphorylation of mTOR, therefore affecting the assembly of mTORC1 complex and mTOR signaling pathway.

Pedicled ligament flaps during pancreatoduodenectomy are associated with reduced hemorrhage from hepatic artery and gastroduodenal artery stump during pancreatoduodenectomy: a systematic review, meta-analysis and trial sequential analysis.

BACKGROUND: The aim of this study was to investigate whether pedicled ligament flaps (PLF) covering around the hepatic and gastroduodenal artery stump can provide better clinical outcomes in pancreatoduodenectomy (PD). METHODS: We conducted a comprehensive search of databases (inception to January 2023) to identify studies comparing PD with or without PLF covering the skeletonized arteries. The perioperative and postoperative outcomes were compared. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated using fixed-effects models. RESULTS: Ten studies were included in the qualitative synthesis. Six studies with 3538 patients met the inclusion criteria for the meta-analysis. Patients in the PLF group had a significantly lower rate of PPH from the hepatic artery or gastroduodenal artery stump (H/G PPH) (OR: 0.41; 95 % CI, 0.22-0.75; P < 0.01) and overall PPH (OR: 0.65; 95 % CI, 0.46-0.93; P = 0.02). There were no significant differences between the two groups in terms of morbidity, grade B/C postoperative pancreatic fistula (B/C POPF), delayed gastric emptying (DGE), reoperation, or mortality. CONCLUSION: Prophylactic pedicled ligament flaps covering around the skeletonized arteries significantly reduced overall PPH and H/G PPH, and it seemed to have no obvious influence on other complications.

Splenic vessels preserving versus Warshaw technique in spleen preserving distal pancreatectomy: A systematic review and meta-analysis.

BACKGROUND: Spleen-preserving distal pancreatectomy is widely used to remove benign or low-grade malignant neoplasms located in the pancreatic body and tail. Both splenic vessels preserving (SVP-DP) and splenic vessels ligating (Warshaw technique [WT]) distal pancreatectomy are safe and effective methods but which technique is superior remains controversial. Thus, this study aimed to evaluate the clinical outcomes of patients who underwent both methods. MATERIAL AND METHODS: Major databases, including PubMed, Embase, Science Citation Index Expanded, and The Cochrane Library, were searched for studies comparing SVP-DP and the WT for spleen-preserving distal pancreatectomy up to December 2021. The perioperative and postoperative outcomes were compared between the SVP-DP and WT groups. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. RESULTS: Twenty retrospective studies with 2173 patients were analyzed. A total of 1467 (67.5%) patients underwent SVP-DP, while 706 (32.5%) patients underwent WT. Patients in the SVP-DP group had a significantly lower rate of splenic infarction (OR: 0.17; 95% CI, 0.11-0.25; P < 0.00001) and incidence of gastric varices (OR: 0.19; 95% CI, 0.11-0.32; P < 0.00001) compared to the patients in the WT group; furthermore, they had a shorter length of hospital stay (WMD: 0.71; 95% CI, -1.13 to -0.29; P = 0.0008). There were no significant differences between the two groups in terms of major complication, postoperative pancreatic fistula (B/C), reoperation, blood loss, or operation time. CONCLUSIONS: Compared to WT, SVP-DP should be preferred to reduce splenic infarction and gastric varices, and WT may be more suitable for large tumors. Moreover, considering the shortcomings of retrospective study, a multicenter randomized controlled study with a large sample size should be conducted to verify our results.

Optimal extent of lymphadenectomy for radical surgery of pancreatic head adenocarcinoma: 2-year survival rate results of single-center, prospective, randomized controlled study.

BACKGROUND: Radical pancreaticoduodenectomy is the only possible cure for pancreatic head adenocarcinoma, and although several RCT studies have suggested the extent of lymph node dissection, this issue remains controversial. This article wanted to evaluate the survival benefit of different lymph node dissection extent for radical surgical treatment of pancreatic head adenocarcinoma. METHODS: A total of 240 patients were assessed for eligibility in the study, 212 of whom were randomly divided into standard lymphadenectomy group (SG) or extended lymphadenectomy group (EG), there were 97 patients in SG and 95 patients in EG receiving the radical pancreaticoduodenectomy. RESULT: The demography, histopathology and clinical characteristics were similar between the 2 groups. The 2-year overall survival rate in the SG was higher than the EG (39.5% vs 25.3%; P = .034). The 2-year overall survival rate in the SG who received postoperative adjuvant chemotherapy was higher than the EG (60.7% vs 37.1%; P = .021). There was no significant difference in the overall incidence of complications between the 2 groups (P = .502). The overall recurrence rate in the SG and EG (70.7% vs 77.5%; P = .349), and the patterns of recurrence between 2 groups were no significant differences. CONCLUSION: In multimodality therapy system, the efficacy of chemotherapy should be based on the appropriate lymphadenectomy extent, and the standard extent of lymphadenectomy is optimal for resectable pancreatic head adenocarcinoma. The postoperative slowing of peripheral blood lymphocyte recovery might be 1 of the reasons why extended lymphadenectomy did not result in survival benefits. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT02928081) in October 7, 2016. https://clinicaltrials.gov/.

3D biomechanical properties of the layered esophagus: Fung-type SEF and new constitutive model.

BACKGROUND AND PURPOSE: Most current studies on the passive biomechanical properties of esophageal tissues directly use the exponential strain energy function (SEF) to fit and calculate the constants of the constitutive equation. In the context of the extensive application of exponential SEF, in-depth research on the exponential SEF is still lacking. The purpose of this study is to combine the exponential function with the polynomial SEF to obtain the most suitable constitutive equation to describe the three-dimensional passive behavior of the esophagus. METHODS: fresh pig esophagus with a length of 13 cm in the middle position was selected as esophageal samples. The esophageal sample was separated into muscular layer and mucosal layer with surgical scissors. Stretch-inflation mechanical tests of the intact esophagus, esophageal muscular, and esophageal mucosa were carried out on a triaxial test machine. The external radius, axial force, and internal pressure were recorded simultaneously. The seven-parameter Fung-type SEF and several new SEFs combining polynomials and exponents were used to fit the experimental data curves. RESULTS: The stretch-inflation test data and the morphometric parameters at the zero-stress state of the layered esophagus were obtained. The new SEF with polynomial and exponential combination is more suitable to describe describing the three-dimensional passive biomechanical properties of esophageal tissue. Among them, New-Fung13 SEF is more suitable for describing the passive biomechanical properties of intact esophageal tissue, Sokolis-Fung13 SEF is more suitable for the esophageal muscle layer, and New-Fung10 SEF is more suitable for the esophageal mucosa. The constitutive parameters of the optimal constitutive model for each layer of the esophagus were obtained.

Immunotherapy-Associated Pancreatic Adverse Events: Current Understanding of Their Mechanism, Diagnosis, and Management.

Immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 (PD-1) and its ligand PD-L1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are involved in T cell-mediated immune response augmentation and promote anti-tumor immunity. Cancer patients treated with combination of immunotherapy, chemotherapy, radiotherapy, and targeted therapy exhibit superior clinical outcomes and tolerance compared with patients treated with monotherapies. However, immutherapy is associated with several concomitant immune-related adverse events (irAEs). For instance, IrAEs interferes with function of gastrointestinal tract, endocrine, dermatological, nervous system and musculoskeletal systems. ICIs-associated pancreatic injury might causes decrease in endocrine and exocrine pancreatic function, resulting in metabolic and nutritional disorders. Clinicians who administer immune checkpoint inhibitors to cancer patients are diagnosed with hyperglycemia, abdominal pain and steatorrhea. Currently, the precise mechanism of ICIs-associated pancreatic injury has not been fully explored. This paper summarizes incidence, diagnosis, clinical characteristics, potential mechanisms, and treatment management patterns of ICIs-associated pancreatic AEs based on previous studies. In addition, possible management approaches of these adverse effects are presented in this paper. in the findings summarized in this paper lay a basis for management of ICIs-associated pancreatic AEs and expanding future immunotherapy applications.

Dihydroartemisinin/miR-29b combination therapy increases the pro-apoptotic effect of dihydroartemisinin on cholangiocarcinoma cell lines by regulating Mcl-1 expression.

BACKGROUND: Cholangiocarcinoma is a malignant tumor that originates from the neoplastic transformation of bile duct epithelial cells. OBJECTIVES: To investigate the role of DHA and miR-29b on the proliferation and apoptosis of cholangiocarcinoma cells, and to explore whether DHA exerted its role through the miR-29b/Mcl-1 signaling pathway. MATERIAL AND METHODS: Human cholangiocarcinoma cell lines HUCCT-1 and FRH0201 were treated with dihydroartemisinin (DHA) and DHA+miR-29b. The inhibitory effects of DHA and miR-29b on proliferation were detected using MTT assay. The effects of DHA and miR-29b on apoptosis were detected using flow cytometry (FCM). The mRNA and protein expressions of Mcl-1L and Mcl-1S were evaluated with reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting, respectively. RESULTS: The DHA increased miR-29b expression in HUCCT-1 and FRH201 cells. The MTT assay showed that DHA+miR-29b combination therapy promoted the inhibition effects on the proliferation of HUCCT-1 and FRH201 cells. The FCM results revealed that DHA and miR-29b combination therapy increased the apoptosis of HUCCT-1 and FRH201 cells. The RT-PCR and western blotting analysis found that DHA+miR-29b combination therapy significantly decreased Mcl-1L expression and increased Mcl-1S expression in both HUCCT-1 and FRH201 cells. The Mcl-1S:Mcl-1L ratio was notably higher in the DHA+miR-29b combination therapy group than in the control group and DHA therapy group, in both HUCCT-1 and FRH201 cells. CONCLUSIONS: The DHA and miR-29b have a pro-apoptotic effect on cholangiocarcinoma cells through the DHA/miR-29b/Mcl-1 pathway, possibly by upregulating the expression of the pro-apoptotic protein Mcl-1S and thus increasing the proportion of Mcl-1S protein among the total amount of Mcl-1 protein.

Laparoscopic spleen-preserving distal versus central pancreatectomy for tumors in the pancreatic neck and proximal body.

For benign and borderline tumors in the pancreatic neck and proximal body, laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and laparoscopic central pancreatectomy (LCP) are alternative surgical procedures. Choosing between LSPDP and LCP is difficult. This retrospective cohort study was looking forward to provide evidence for clinical decision.A total of 59 patients undergoing LSPDP (Kimura procedure) and LCP between June 2013 and March 2017 were selected. The clinical outcomes of patients were compared by χ test or Fisher exact test and Student t test.This study included 36 patients in LSPDP group, and 23 patients in LCP group. The overall complications incidence in LCP group was significantly higher than LSPDP group (35 vs 6%, P = .004), and the postoperative pancreatic fistula (POPF) (grade B and C) rate and abdominal infection rate in LCP group were still significantly higher than LSPDP group (POPF 22 vs 3%, P = .019; abdominal infection 35 vs 3%, P = .001, respectively). The length of resected pancreas was significantly longer in LSPDP group (9.8 ±â€Š2.0 vs 5.3 ±â€Š1.1 cm, P = .007). The median follow-up was 39 months (range 12-57 months). No patient was confronted by tumor recurrence. The proportion of postoperative pancreatin and insulin treatment in LCP group were similar to LSPDP group (9 vs 17%, P = .383; 0 vs 3%, P = 1.000, respectively).For patients with poor general condition, the safety of LCP needs to be taken seriously; in some ways, LSPDP may be more secure, physiological, and easier operation for tumor located in pancreatic neck and proximal body.

Preventive effects of ulinastatin on complications related to pancreaticoduodenectomy: A Consort-prospective, randomized, double-blind, placebo-controlled trial.

Postoperative pancreatic fistula (POPF) is one of the most common major complications after pancreaticoduodenectomy (PD). Ulinastatin is an intrinsic trypsin inhibitor and mainly used to treat acute pancreatitis, chronic recurrent pancreatitis, and acute circulatory failure. The study aims to investigate the efficacy of ulinastatin on pancreatic fistula and other complications after PD. This prospective, randomized, double-blind, placebo-controlled trial was conducted in West China Hospital of Sichuan University from December 2012 to December 2014. A total of 106 consecutive patients undergoing PD were randomly assigned to receive ulinastatin or placebo during and after the surgery for 5 days. Baseline clinical characteristics and outcomes of patients were recorded and analyzed. Ninety-two patients including 42 in the ulinastatin group and 50 in the placebo group were available for outcome assessment. The POPF rates were comparable between ulinastatin group (43%) and placebo group (26%), whereas the severe pancreatic fistula rate (grade B + C) was significantly less in ulinastatin group than that in placebo group (7% vs 24%, P = 0.045). For patients with small pancreatic duct diameter (≤3 mm), ulinastatin could significantly reduce the risk of POPF (P = 0.022). Ulinastatin had protective effects for patients undergoing PD on the prevention of severe postoperative pancreatic fistula.

Role of original and modified Frey's procedures in chronic pancreatitis.

AIM: To retrospectively review patients with chronic pancreatitis (CP) treated with Frey's procedures between January 2009 and January 2014. METHODS: A retrospective review was performed of patients with CP treated with Frey's procedures between January 2009 and January 2014 in the Department of Pancreatic Surgery. A cross-sectional study of postoperative pain relief, quality of life (QoL), and alcohol and nicotine abuse was performed by clinical interview, letters and telephone interview in January 2016. QoL of patients was evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0. The patients were requested to fill in the questionnaires by themselves via correspondence or clinical interview. RESULTS: A total of 80 patients were enrolled for analysis, including 44 who underwent the original Frey's procedure and 36 who underwent a modified Frey's procedure. The mean age was 46 years in the original group and 48 years in the modified group. Thirty-five male patients (80%) were in the original group and 33 (92%) in the modified group. There were no differences in the operating time, blood loss, and postoperative morbidity and mortality between the two groups. The mean follow-up was 50.3 mo in the original group and 48.7 mo in the modified group. There were no differences in endocrine and exocrine function preservation between the two groups. The original Frey's procedure resulted in significantly better pain relief, as shown by 5-year follow-up (P = 0.032), better emotional status (P = 0.047) and fewer fatigue symptoms (P = 0.028). When stratifying these patients by the M-ANNHEIM severity index, no impact was found on pain relief after the two types of surgery. CONCLUSION: The original Frey's procedure is as safe as the modified procedure, but the former yields better pain relief. The severity of CP does not affect postoperative pain relief.

Single center experience in selecting the laparoscopic Frey procedure for chronic pancreatitis.

AIM: To share our experience regarding the laparoscopic Frey procedure for chronic pancreatitis (CP) and patient selection. METHODS: All consecutive patients undergoing duodenum-preserving pancreatic head resection from July 2013 to July 2014 were reviewed and those undergoing the Frey procedure for CP were included in this study. Data on age, gender, body mass index (BMI), American Society of Anesthesiologists score, imaging findings, inflammatory index (white blood cells, interleukin (IL)-6, and C-reaction protein), visual analogue score score during hospitalization and outpatient visit, history of CP, operative time, estimated blood loss, and postoperative data (postoperative mortality and morbidity, postoperative length of hospital stay) were obtained for patients undergoing laparoscopic surgery. The open surgery cases in this study were analyzed for risk factors related to extensive bleeding, which was the major reason for conversion during the laparoscopic procedure. Age, gender, etiology, imaging findings, amylase level, complications due to pancreatitis, functional insufficiency, and history of CP were assessed in these patients. RESULTS: Nine laparoscopic and 37 open Frey procedures were analyzed. Of the 46 patients, 39 were male (85%) and seven were female (16%). The etiology of CP was alcohol in 32 patients (70%) and idiopathic in 14 patients (30%). Stones were found in 38 patients (83%). An inflammatory mass was found in five patients (11%). The time from diagnosis of CP to the Frey procedure was 39 ± 19 (9-85) mo. The BMI of patients in the laparoscopic group was 20.4 ± 1.7 (17.8-22.4) kg/m(2) and was 20.6 ± 2.9 (15.4-27.7) kg/m(2) in the open group. All patients required analgesic medication for abdominal pain. Frequent acute pancreatitis or severe abdominal pain due to acute exacerbation occurred in 20 patients (43%). Pre-operative complications due to pancreatitis were observed in 18 patients (39%). Pancreatic functional insufficiency was observed in 14 patients (30%). Two laparoscopic patients (2/9) were converted. In seven successful laparoscopic cases, the mean operative time was 323 ± 29 (290-370) min. Estimated intra-operative blood loss was 57 ± 14 (40-80) mL. One patient had a postoperative complication, and no mortality was observed. Postoperative hospital stay was 7 ± 2 (5-11) d. Multiple linear regression analysis of 37 open Frey procedures showed that an inflammatory mass (P < 0.001) and acute exacerbation (P < 0.001) were risk factors for intra-operative blood loss. CONCLUSION: The laparoscopic Frey procedure for CP is feasible but only suitable in carefully selected patients.

Outcome and costs of laparoscopic pancreaticoduodenectomy during the initial learning curve vs laparotomy.

AIM: To compare laparoscopic pancreaticoduodenectomy (TLPD) during the initial learning curve with open pancreaticoduodenectomy in terms of outcome and costs. METHODS: This is a retrospective review of the consecutive patients who underwent TLPD between December 2009 and April 2014 at our institution. The experiences of the initial 15 consecutive TLPD cases, considered as the initial learning curve of each surgeon, were compared with the same number of consecutive laparotomy cases with the same spectrum of diseases in terms of outcome and costs. Laparoscopic patients with conversion to open surgery were excluded. Preoperative demographic and comorbidity data were obtained. Postoperative data on intestinal movement, pain score, mortality, complications, and costs were obtained for analysis. Complications related to surgery included pneumonia, intra-abdominal abscess, postpancreatectomy hemorrhage, biliary leak, pancreatic fistula, delayed gastric emptying, and multiple organ dysfunction syndrome. The total costs consisted of cost of surgery, anesthesia, and admission examination. RESULTS: A total of 60 patients, including 30 consecutive laparoscopic cases and 30 consecutive open cases, were enrolled for review. Demographic and comorbidity characteristics of the two groups were similar. TLPD required a significantly longer operative time (513.17 ± 56.13 min vs 371.67 ± 85.53 min, P < 0.001). The TLPD group had significantly fewer mean numbers of days until bowel sounds returned (2.03 ± 0.55 d vs 3.83 ± 0.59 d, P < 0.001) and exhaustion (4.17 ± 0.75 d vs 5.37 ± 0.81 d, P < 0.001). The mean visual analogue score on postoperative day 4 was less in the TLPD group (3.5 ± 9.7 vs 4.47 ± 1.11, P < 0.05). No differences in surgery-related morbidities and mortality were observed between the two groups. Patients in the TLPD group recovered more quickly and required a shorter hospital stay after surgery (9.97 ± 3.74 d vs 11.87 ± 4.72 d, P < 0.05). A significant difference in the total cost was found between the two groups (TLPD 81317.43 ± 2027.60 RMB vs laparotomy 78433.23 ± 5788.12 RMB, P < 0.05). TLPD had a statistically higher cost for both surgery (24732.13 ± 929.28 RMB vs 19317.53 ± 795.94 RMB, P < 0.001) and anesthesia (6192.37 ± 272.77 RMB vs 5184.10 ± 146.93 RMB, P < 0.001), but a reduced cost for admission examination (50392.93 ± 1761.22 RMB vs 53931.60 ± 5556.94 RMB, P < 0.05). CONCLUSION: TLPD is safe when performed by experienced pancreatobiliary surgeons during the initial learning curve, but has a higher cost than open pancreaticoduodenectomy.

Upregulation of the MCL-1S protein variant following dihydroartemisinin treatment induces apoptosis in cholangiocarcinoma cells.

The aim of the present study was to determine whether dihydroartemisinin (DHA) induces apoptosis in the human cholangiocarcinoma QBC939 cell line through the regulation of myeloid cell leukemia-1 (MCL-1) expression. The inhibitory rates of DHA on QBC939 cell proliferation and the effects of DHA on the cell death rates at various DHA concentrations and following various treatment times were examined. The rate of apoptosis and cell cycle changes following DHA treatment were examined and the changes in the expression of MCL-1 mRNAs and MCL-1 proteins following DHA treatment were also examined. The MTT assay and trypan blue staining demonstrated that DHA significantly inhibited the proliferation (P<0.05) and promoted the death of QBC939 cells (P<0.05). The DNA ladder assay and flow cytometry (FCM) analysis demonstrated that the rate of apoptosis in the experimental group was significantly increased following DHA treatment (P<0.01). FCM analysis also demonstrated that DHA treatment led to a reduction in the percentage of QBC939 cells in the G0/G1 and G2/M phases, and the majority of the DNA-treated cells were arrested in the S phase of the cell cycle (P<0.01). Western blot analysis demonstrated that DHA treatment significantly upregulated the expression of the pro-apoptotic MCL-1S protein. In contrast, no significant difference in the expression of the anti-apoptotic MCL-1L protein was observed following DHA treatment. DHA affected the expression of the apoptosis-associated protein MCL-1 through multiple mechanisms. DHA treatment increased the ratio of MCL-1S/MCL-1L protein, thus inducing apoptosis in cholangiocarcinoma cells.

Losartan supports liver regrowth via distinct boost of portal vein pressure in rodents with 90 % portal branch ligation.

OBJECTIVES: The study used a model of 90 % portal branch ligation (PBL) in rats to study the effect of losartan on portal vein pressure (PVP) and liver regeneration in rats after PBL. METHODS: A total of 144 male Sprague-Dawley rats were arbitrarily designated into three treatment method groups: a sham operation group (Sham), a PBL treatment group (PBL), and a PBL plus losartan treatment group (PBL + L). Losartan (2 mg/day) was intragastrically gavaged 3 days before the PBL or sham operation to time points of study. RESULTS: Both the PBL and PBL + L groups showed an intense surge in PVP after PBL treatment, peaking at 12 h postsurgery, then lessening progressively afterwards. PVP was substantially greater in these two groups compared with the Sham group at 6-72 h postsurgery (p < 0.01). Compared with the PBL group, the PBL + L group showed a noticeable reduction in PVP 6-48 h postsurgery (p < 0.05); the PBL group showed considerably raised levels of plasma ALT and AST 6-72 h postsurgery (p < 0.01). Compared to the PBL group, the PBL + L group showed drastically reduced plasma ALT and AST levels 12-72 h postsurgery (p < 0.05). CONCLUSIONS: Losartan supports liver regeneration in 90 % of rats that underwent PBL. The mechanism may be related to losartan's ability to regulate PVP and increase serum hepatocyte growth factor levels.

[Effect of 90 percentage portal branch ligation on liver regeneration and expression of metalloproteinase and tissue inhibitors of metalloproteinases in rats].

OBJECTIVE: To investigate the effect of 90% portal branch ligation on liver regeneration and expression of metalloproteinases and tissue inhibitors of metalloproteinases in rats. METHODS: Ninety-six SD rats were randomly divided into Sham-PBL group and portal vein branches ligation group. The weight of both ligated and unligated lobes of liver were measured at post operation day (POD) 0.5, 1, 3, 5, 7, 14, 21 and 28. The morphological changes of the non-ligated liver lobes were observed by microscope. The expression of PCNA, MMP2, MMP9 and TIMP2 of the non-ligated liver lobes were studied by immunohistochemistry. RESULTS: 1) 95.8% rats survived from the ligation of 90% portal branch. Hepatic lobe at the ligated side diminished progressively after ligation, whereas the lobes of the unligated side underwent compensatory regeneration. The ratio of non-ligated lobes weight to the whole liver increased slowly within 1d, speeded up significantly during 1-5d period, increased slowly after POD5, and got the plateau stag at POD7; 2) PCNA index were markedly increased within POD 0.5-3 (P < 0.01). It reached the peak at POD5 and decreased slightly at POD7, but still higher than Sham-PBL group level, then gradually returned to normal. 3) The expression of MMP2,MMP9 and TIMP2 in the non-ligated liver lobes were markedly increased at 1d. It reached the peak at POD7 and gradually returned to normal within POD7-28. 4) The MMP2 and PCNA in liver had a positive correlation at POD 0.5, 1, 5, 7, 14. The expressions of MMP9 and PCNA had a positive correlation at POD 0.5, 1, 7, 21. CONCLUSION: The expressions of TIMP2 and PCNA had a positive correlation at POD1, 7, 14, 21. The expression of MMP2, MMP9 and TIMP2 of the non-ligated liver lobes is markedly increased at POD1. It reaches the peak at POD7, and dropped to normal level gradually. The expressions of MMP2, MMP9 and TIMP2 and PCNA were correlated in 90% portal branch Ligation rats. The expression of MMP2,MMP9 and TIMP2 may play a pivotal role in liver regeneration.

[Effect of hepatocyte growth factor on intestinal permeability and bacterial translocation after small bowel transplantation in rat].

OBJECTIVE: To evaluate the effect of hepatocyte growth factor (HGF) on intestinal permeability and bacterial translocation after small bowel transplantation in rats. METHODS: Twenty Wistar rats were as receptors and twenty SD rats as donors. After heterotopic intestinal grafting, cyclosporine A was administered at 6 mg/kg x day intramuscularly for inhibiting rejection. The SD rats were divided into 2 groups (n = 10). HGF was administered at 150 microg/kg x day (HGF group) and normal saline was administered at 150 microg/kg x day (control group). Intestinal permeability and bacterial translocation to the mesenteric lymph nodes and portal vein were assessed at the 8th postoperative day. RESULTS: The lactulose and lactulose/ mannitol of control group (0.0931%+/-0.0085% and 0.132+/-0.021) were higher than those of normal reference value (0.0150%+/-0.0020% and 0.020+/-0.005) (P < 0.05). The lactulose and lactulose/ mannitol of HGF group (0.0396%+/-0.0090% and 0.056+/-0.013) were also higher than those of normal reference value (P<0.05). The bacterial culture positive proportion of lymphaden in HGF group and control group were 10% and 60%, showing statistically significant difference (P<0.05). The bacterial culture positive proportion of portal vein in HGF group and control group were 10% and 20% respectively (P>0.05). CONCLUSION: HGF can decrease intestinal permeability and bacterial translocation from the lumen of the graft to the mesenteric lymph nodes, thus improve gut barrier function, may be of help to reduce the incidence of septic complications after intestinal grafting.

[Protective effect of epidermal growth factor on isograft mucosal structure after small bowel transplantation in rat].

OBJECTIVE: To investigate the effects of epidermal growth factor(EGF) on mucosal structure after small bowel transplantation in rat. METHODS: Total small bowel transplantation was performed in inbred Wistar(RT1k) rats heterotopically, either total parenteral nutrition(control group, n=10) or TPN supplemented with epidermal growth factor(EGF group, n=10) was given to the recipients from the second day to 10th day after operation. The changes of morphology, ultrastructure, mucosal protein and DNA contents were determined. RESULTS: The height of mucosal villus,the depth of crypt, the thickness of mucosa and the surface area of villus were (284.47+/-31.58)microm, (98.78+/-10.83 microm, (389.56+/-31.72)microm and (0.089+/-0.009 )mm(2) respectively in EGF group,and (176.45+/-14.62)microm, (74.45+/-8.34)microm, (259.38+/-24.65) microm, and (0.041+/-0.005)mm2 respectively in the control group. The morphological parameters were significantly higher in EGF group than those in the control group. Mucosal protein content was (84.65+/-8.32)mg/g wet wt in EGF group,significantly higher than (53.73+/- 11.45) mg/g wet wt in the control group(P=0.012). DNA content was also significantly higher in EGF group than that in the control group. [(0.86+/0.10)mg/g wet wt vs (0.51+/-0.06)mg/g wet wt, P=0.008]. Nearly normal ultrastructure of the graft enterocyte was maintained in EGF group, while atrophic microvilli and broken mitochondrial crista were observed in the control group. CONCLUSION: EGF can preserve the mucosal structure of the graft, maintain the integrity of the ultrastructure of graft enterocyte after small bowel transplantation in rat.