EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma.

A synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment.

Analysis of 300 consecutive cases of pancreatic adenocarcinoma in a single-center in China.

BACKGROUND: Most of the reports on the prognostic indicators of patients with pancreatic adenocarcinoma are from developed countries. The present study focused on the prognostic indicators of Chinese patients with pancreatic adenocarcinoma. METHODS: A total of 300 patients with pancreatic adenocarcinoma who had undergone curative resection were included. The resection and R0/R1 resection rates for adenocarcinomas from different parts of the pancreas were calculated and clinical characteristics were analyzed. RESULTS: In 3427 patients diagnosed with pancreatic adenocarcinomas, only 300 (8.8%) were eligible for radical resection. The total median survival of these patients was 19 months, and their 1-, 3-, and 5-year survival rates were 72.5%, 28.0% and 23.4%, respectively. The prognostic factors included socioeconomic status, smoking history, symptoms, high blood glucose, and various tumor characteristics, including perineural and vascular invasion, lymph node metastases, and CA19-9 levels before and after operation. Operation-associated prognostic indicators included operation time, blood loss and transfusions, pancreatic fistula, and complications. Independent predictors of mortality included poor socioeconomic status, smoking history, symptoms, CA19-9, perineural invasion and lymph node metastasis, grade of fistula and complications. Patient survival was not correlated with either resection margin or adjuvant chemotherapy in multivariate analysis. CONCLUSIONS: The survival rates of patients with curative resection for pancreatic adenocarcinoma in China are close to those in developed countries, but curative resection rate is far below. Socioeconomic status, symptoms, and CA19-9 are the three most prominent prognostic factors, which are helpful in patient selection and perioperative care.

[Analysis of predisposing factors for pancreatic fistula after pancreaticoduodenectomy].

OBJECTIVE: To analyze the predisposing factors for pancreatic fistula after pancreaticoduodenectomy. METHODS: The clinical data of 323 patients undergoing pancreaticoduodenectomy from January 2007 to March 2012 were analyzed retrospectively. There were 185 male and 138 female patients, aging from 27 to 82 years. All the patients were devided into pancreatic fistula group (n = 52) and non-pancreatic fistula group (n = 271). Twenty variables, such as age, sex, primary disease, alcohol abuse, cholangitis, bilirubin, albumin, hemoglobin, operating time, blood loss, transfusion, texture of the remnant pancreas, diameter of wirsung, drainages of pancreatic duct, specialized group which potentially affect the incidence, were analyzed by t test for continuous variables and χ(2) test for discrete variables. The variables with significance (P < 0.05) were then analyzed with Logistic regression model. RESULTS: Of all the 323 patients, the overall morbidity rate was 30.3% (98/323), and the mortality was 3.7% (12/323). Pancreatic fistula rate was 16.1% (52/323), 7 patients died for pancreatic fistula PF. In univariate analysis, primary disease, preoperative high bilirubin level, intraoperative blood loss and transfusion, texture of the remnant pancreas, diameter of wirsung, drainages of pancreatic duct, specialized group had significant difference between two groups (χ(2) = 4.072 to 9.008, P < 0.05). Multivariate logistic regression analysis revealed that primary disease (OR = 2.091, P = 0.001), texture of the remnant pancreas (OR = 7.715, P = 0.040), diameter of wirsung (OR = 5.405, P = 0.006), pancreatic duct stent (OR = 4.313, P = 0.001) and specialized group (OR = 6.404, P = 0.006) were independent risk factors in pancreatic fistula. CONCLUSIONS: Primary disease, texture of the remnant pancreas, diameter of wirsung, pancreatic duct stent and specialized group are independent risk factors in pancreatic fistula. With the purpose of decreasing pancreatic fistula rate after PD, it is necessary to operate meticulously and precisely, place external pancreatic duct stent and establish pancreatic center or specialized group.

[The clinical analysis of a step-up approach for severe acute pancreatitis: report of 121 cases].

OBJECTIVE: To investigate the feasibility and clinical value of the step-up approach for severe acute pancreatitis (SAP). METHODS: Clinical data of 121 SAP patients admitted between January 2002 and December 2011 were retrospectively analyzed. Fifty-eight patients (37 males and 21 females, aged from 20 to 72 years, mean 47.6 years) in the group of direct open necrosectomy from January 2002 to December 2006 were performed laparotomy through removal of all necrotic tissue. Sixty-three patients (42 males and 21 females, aged from 19 to 78 years, mean 46.2 years) of step-up approach from January 2007 to December 2011 underwent percutaneous catheter drainage through retroperitoneum or omental bursa guided by B-type ultrasonography for the first therapy, and then, according to the pathogenetic condition, if necessary, followed by a small incisional necrosectomy along the drainage tube. The two groups were compared for the rates of postoperative complications, death, transfusion and length of stay, medical costs. RESULTS: The rates of total postoperative complications, organ dysfunction, alimentary tract fistula and incisional hernia in step-up approach group were significantly lower than those of direct open necrosectomy group (31.7% vs. 62.1%, 14.3% vs. 37.5%, 6.3% vs. 19.0%, 9.5% vs. 29.3%; χ(2) = 4.43 to 11.17, P = 0.001 to 0.035). The other complications had no significant differences between the two groups (P > 0.05). Patients in step-up approach group had a lower rates of transfusion (44.4% vs. 70.7%, χ(2) = 8.488, P = 0.004), fewer medical costs of transfusion and hospital stay, compared with those in direct open necrosectomy group ((2525 ± 4573) yuan vs. (4770 ± 6867) yuan, t = 2.131, P = 0.035; (171 213 ± 50 917) yuan vs. (237 874 ± 67 832) yuan, t = 2.496, P = 0.014). There were no significant differences of length of stay and mortality between two groups (P > 0.05). CONCLUSION: Step-up approach for SAP which can reduce the rates of postoperative complications, transfusion and medical costs has significant feasibility and great clinical value.

[Experimental study of the function of nuclear factor-κB-dependent epithelial to mesenchymal transition in pancreatic cancer cells under hypoxic conditions].

OBJECTIVE: To investigate the function of nuclear factor (NF)-κB in the epithelial to mesenchymal transition induced by hypoxia in pancreatic cancer cells. METHODS: For cultured pancreatic cancer cells (BxPC-3 and Panc-1) under hypoxic and normoxic conditions, the differences in the morphology were observed by optical microscope. The expression of markers of epithelial and mesenchymal phenotypes, E-cadherin, vimentin and N-cadherin, were determined by Western blot. NF-κB P65 activity was measured by electrophoretic mobility shift assay. Invasion and gemcitabine resistance of pancreatic cancer cells were evaluated in matrigel invasion assay and cell counting kit-8 assay. Both molecular and pharmacologic means of inhibiting NF-κB P65 were used in these hypoxic cells and then the above resulting phenotypes were compared with those of the control-treated cells. RESULTS: After cultured pancreatic cancer cells under hypoxic conditions for 48 h, normoxic cells exhibited a polygonal shape and formed tight clusters of cells, whereas hypoxic cells took on an elongated, fibroblastoid morphology associated with a more highly invasive character and resistance to gemcitabine; hypoxic cells exhibited an suppression of E-cadherin and increase in vimentin and N-cadherin expression. NF-κB P65 activity was elevated in hypoxic cells. On the contrary, on molecular or pharmacologic inhibition of NF-κB P65, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive and drug resistant phenotype. CONCLUSIONS: Pancreatic cancer cells underwent epithelial to mesenchymal transition exposed to hypoxia, exhibited highly invasive and drug resistant phenotype. Inhibition of NF-κB P65 under hypoxic conditions, pancreatic cancer cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive and drug resistant phenotype.

Matrine inhibits breast cancer growth via miR-21/PTEN/Akt pathway in MCF-7 cells.

BACKGROUND: Matrine is one of the major alkaloids extracted from Sophora flavescens and has been used clinically for breast cancer with notable therapeutic efficacy in China. However, the mechanisms are still largely unknown. METHODS: Cell viability was analyzed by MTT assay. After MCF-7 cells were treated with matrine for 48h, apoptosis was detected by flow cytometry, TUNEL assay and transmission electron microscopy, and the cell cycle distribution was also analyzed by flow cytometry. Further, the expression of PTEN, pAkt, Akt, pBad, Bad, p21(/WAF1/CIP1), and p27(/KIP1) was determined by Western blot. Changes of miR-21 level were quantified by real-time RT-PCR. After miR-21 was transfected in MCF-7 cells, PTEN protein level was measured by Western blot. RESULTS: Matrine inhibited MCF-7 cell growth in a concentration-and time-dependent manner, by inducing apoptosis and cell cycle arrest at G(1)/S phase. Matrine up-regulated PTEN by downregulating miR-21 which in turn dephosphorylated Akt, resulting in accumulation of Bad, p21(/WAF1/CIP1) and p27(/KIP1). CONCLUSION: Our study unraveled, for the first time, the ability of matrine to suppress breast cancer growth and elucidated the miR-21/PTEN/Akt pathway as a signaling mechanism for the anti-cancer action of matrine. Our findings also reinforce the notion that miRNAs can act as mediators of the therapeutic efficacy of natural medicines.

Precise hepatectomy guided by minimally invasive surgery: a novel strategy for liver resection.

Liver resection has been established currently as an effective and standard treatment for patients suffering from both benign and malignant hepatobiliary diseases. Although substantial improvement in perioperative mortality rate and morbidity resulting from appropriate candidates selection, advanced surgical techniques and enhanced perioperative care, hepatectomy is still burdened by about 5% mortality rate and some lethal postoperative complications, especially postoperative liver insufficiency and failure. Various approaches have been advocated to minimize stress and insult on patients due to operative procedures. It becomes important to preserve remnant hepatic function as much as possible to improve the outcome of hepatectomy. Minimally invasive concept and fast track surgery are crucial breakthrough in the natural history of surgery and have been employed in liver resection. To safely and accurately perform hepatic resection, owing to our experiences with recent advances in surgical techniques and perioperative administration for liver resection, a novel strategy, "precise hepatectomy" originating from minimally invasive surgery has been developed, which includes precise preoperative planning, sophisticated intraoperative techniques and careful postoperative management. This strategy is characteristic by involvement of minimally invasive concept in overall therapy, from preoperative assessment to postoperative care, optimization of a series of advanced techniques and proper employment of surgical instruments in light of actual individual information. However, further prospective studies, especially randomized controlled trials in high volume centers, remain essential to compare the safety and therapeutic efficacies between precise hepatectomy and conventional surgical procedures.

Dihydroartemisinin enhances Apo2L/TRAIL-mediated apoptosis in pancreatic cancer cells via ROS-mediated up-regulation of death receptor 5.

BACKGROUND: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Apo2 ligand or tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is regarded as a promising anticancer agent, but chemoresistance affects its efficacy as a treatment strategy. Apoptosis induced by the combination of DHA and Apo2L/TRAIL has not been well documented, and the mechanisms involved remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that DHA enhances the efficacy of Apo2L/TRAIL for the treatment of pancreatic cancer. We found that combined therapy using DHA and Apo2L/TRAIL significantly enhanced apoptosis in BxPC-3 and PANC-1 cells compared with single-agent treatment in vitro. The effect of DHA was mediated through the generation of reactive oxygen species, the induction of death receptor 5 (DR5) and the modulation of apoptosis-related proteins. However, N-acetyl cysteine significantly reduced the enhanced apoptosis observed with the combination of DHA and Apo2L/TRAIL. In addition, knockdown of DR5 by small interfering RNA also significantly reduced the amount of apoptosis induced by DHA and Apo2L/TRAIL. CONCLUSIONS/SIGNIFICANCE: These results suggest that DHA enhances Apo2L/TRAIL-mediated apoptosis in human pancreatic cancer cells through reactive oxygen species-mediated up-regulation of DR5.

Expression and prognostic value of ING3 in human primary hepatocellular carcinoma.

The tumor-suppressor ING3 has been shown to be involved in tumor transcriptional regulation, apoptosis and the cell cycle. Some studies have demonstrated that ING3 is dysregulated in several types of cancers. However, the expression and function of ING3 in human hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate ING3 expression in hepatic tumors and its clinical relevance in hepatic cancer. The expression of ING3 protein was examined in 120 dissected HCC tissues and 47 liver tissues adjacent to the tumor by immunohistochemical assays and confirmed by Western blot analysis in 20 paired frozen tumor and non-tumor liver tissues. The relationship between ING3 staining and clinico-pathological characteristics of HCC was further analyzed. The mRNA expression of ING3 in the dissected tissues was also analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and realtime PCR. Both mRNA and protein concentrations of ING3 were found to be downregulated in the majority of HCC tumors in comparison with matched non-tumor hepatic tissues. Analysis of the relationship between ING3 staining and clinico-pathological characteristics of HCC showed that the low expression of ING3 protein is correlated with more aggressive behavior of the tumor. Kaplan-Meier curves demonstrated that patients with a low expression of ING3 have a significantly increased risk of shortened survival time. In addition, multivariate analysis suggested that the level of ING3 expression may be an independent prognostic factor. Our findings indicate that ING3 may be an important marker for human hepatocellular carcinoma progression and prognosis, as well as a potential therapeutic target.

Nuclear factor-κB-dependent epithelial to mesenchymal transition induced by HIF-1α activation in pancreatic cancer cells under hypoxic conditions.

BACKGROUND: Epithelial to mesenchymal transition (EMT) induced by hypoxia is one of the critical causes of treatment failure in different types of human cancers. NF-κB is closely involved in the progression of EMT. Compared with HIF-1α, the correlation between NF-κB and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-κB, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and attenuated their highly invasive and drug-resistant phenotype. Introducing a pcDNA3.0/HIF-1α into pancreatic cancer cells under normoxic conditions heightened NF-κB activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-κB activity in this setting attenuated the EMT phenotype. CONCLUSIONS/SIGNIFICANCE: These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells.

Tetraethylammonium enhances the rectal and colonic motility in rats and human in vitro.

Hirschsprung's disease is the congenital absence of generating the peristaltic contractions transmitting from the proximal colon to rectum. We previously have found that tetraethylammonium (TEA), the nonselective Ca(2+)-activated K(+) channel blocker, increases the maximal contractile force and the amplitude of the contraction in rat duodenum. The present study is to test the effect of TEA on motility of colon and rectum from rats and Hirschsprung's disease patients in vitro, in order to find an alternative method to improve the syndrome of Hirschsprung's disease. The rectal and colonic motility was recorded by a tension transducer connected to a biology function experiment system. Histology was analyzed with standard hematoxylin and eosin staining. TEA (1, 3, and 5 mM) significantly increased the amplitude and frequency of contractility of colon and rectum from rats in longitudinal and circular direction. TEA at 5 and 15 mM concentrations showed no effect on histology of colon and rectum from rats that were administered locally with TEA into colon lumen from anus for 10 days. TEA at 15 mM increased the amplitude and frequency of contractions of the colon and rectum from Hirschsprung's disease patients. Our data showed that TEA increased the contractility of colon and rectum from rats and Hirschsprung's disease patients in vitro, suggesting that local administration of TEA in colon or rectum lumen might be an alternative method to ameliorate the syndrome of Hirschsprung's disease patients who are not cured completely by surgery or not suitable for surgery.

Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-κB pathway.

PURPOSE: Dihydroartemisinin (DHA) has recently shown antitumor activity in human pancreatic cancer cells. However, its effect on antiangiogenic activity in pancreatic cancer is unknown, and the mechanism is unclear. This study was aimed to investigate whether DHA would inhibit angiogenesis in human pancreatic cancer. METHODS: Cell viability and proliferation, tube formation of human umbilical vein endothelial cells (HUVECs), nuclear factor (NF)-κB DNA-binding activity, expressions of vascular endothelial growth factor (VEGF), interleukin (IL)-8, cyclooxygenase (COX)-2, and matrix metalloproteinase (MMP)-9 were examined in vitro. The effect of DHA on antiangiogenic activity in pancreatic cancer was also assessed using BxPC-3 xenografts subcutaneously established in BALB/c nude mice. RESULTS: DHA inhibited cell proliferation and tube formation of HUVECs in a time- and dose-dependent manner and also reduced cell viability in pancreatic cancer cells. DHA significantly inhibited NF-κB DNA-binding activity, so as to tremendously decrease the expression of NF-κB-targeted proangiogenic gene products: VEGF, IL-8, COX-2, and MMP-9 in vitro. In vivo studies, DHA remarkably reduced tumor volume, decreased microvessel density, and down-regulated the expression of NF-κB-related proangiogenic gene products. CONCLUSIONS: Inhibition of NF-κB activation is one of the mechanisms that DHA inhibits angiogenesis in human pancreatic cancer. We also suggest that DHA could be developed as a novel agent against pancreatic cancer.

Expression and prognostic values of Id-1 and Id-3 in gastric adenocarcinoma.

BACKGROUND: Id (inhibitor of differentiation/DNA binding)-1 and -3 are involved in neoangiogenesis; they antagonize basic helix-loop-helix proteins, inhibit differentiation, and enhance cell proliferation. The aim of this study was to investigate Id-1 and -3 expression in gastric tumors and their clinical relevance in gastric cancer. MATERIALS AND METHODS: We investigated Id-1 and Id-3 expression in gastric cancer samples by immunohistochemistry and Western blotting, and further analyzed the relationship between expression of Id-1 and Id-3 and clinicopathologic characteristics. RESULTS: Expression of Id-1 and -3 was found significantly more often in gastric cancers than in matched adjacent nonmalignant tissues. Cancer samples with poor or moderate histologic differentiation showed significantly stronger Id-1 and -3 expression than cancer samples with high differentiation. In cancer samples, strong or moderate expression of Id-3, but not Id-1, was a strong independent predictor for shorter overall survival in multivariate analysis. CONCLUSIONS: The level of Id-1 and -3 protein expression was associated with the malignant potential of gastric tumors. In cancer samples, stronger Id-1 and -3 expression is associated with poor differentiation and more aggressive behavior of tumor cells, resulting in poor clinical outcome. Consequently, Id-3 might be used to independently predict survival of patients with gastric cancer.

microRNA expression alteration after arsenic trioxide treatment in HepG-2 cells.

BACKGROUND AND AIM: More and more microRNA (miRNA) are found to be involved in tumor genesis and progress. Arsenic trioxide has been an effective chemotherapeutic drug in cancer therapy for many years. In this study, we aimed to find the miRNA involved in the mechanisms of arsenic trioxide treatment in cancer therapy. METHODS: We detected the expression profile of miRNA by miRNA microarray and quantitative real-time polymerase chain reaction. Cell viability assay, flow cytometry analysis, prediction of miRNA targets, Western blot analysis and luciferase reporter assay were carried out to determine the role of one selected miRNA, namely mir-29a, in affecting the biological behaviors of HepG-2 cells. RESULTS: Among the 677 human miRNA in the microarray, five miRNA were upregulated and four were downregulated in HepG-2 cells treated with arsenic trioxide compared to their controls. If only changes above two folds were considered, four miRNA were identified, namely miR-24, miR-29a, miR-30a and miR-210, which were all upregulated. Among them, miR-29a showed a positive therapeutic effect in liver cancer cells by inhibiting cell growth and inducing cell apoptosis, and PPM1D was confirmed to be the target gene of miR-29a. Furthermore, a synergy effect was detected between miR-29a and arsenic trioxide. CONCLUSIONS: Arsenic trioxide altered miRNA expression profile in HepG-2 cells. Among the altered miRNA, miR-29a seemed to take a role in the mechanism of arsenic trioxide in liver cancer therapy. The synergy effect between miR-29a and arsenic trioxide may offer this drug a new chance in cancer therapy by decreasing its dose and toxic side-effects.

[Experience of the surgical comprehensive treatment on severe acute pancreatitis].

OBJECTIVE: To summary the experience of the surgical comprehensive treatment of severe acute pancreatitis (SAP). METHODS: From July 1999 to December 2009, a total of 506 patients suffered SAP were admitted with a mean APACHE II score 12.8 ± 4.6. There were 270 male and 236 female, aged from 16 to 89 years, mean age 43 years. SAP patients were treated by the SAP treatment team which consisted of pancreatic specialized and multidisciplinary doctors. Two hundreds and thirty-four cases (46.2%) received non-operative treatment and 272 cases (53.8%) received surgical intervention. RESULTS: In 506 cases, 445 patients were cured and 52 patients died (31 died in early stage, 21 died in later stage), 9 cases discharged automatically. The overall incidence of complication, overall mortality and overall curative rate were 29.4% (149/506), 10.3% (52/506) and 87.9% (445/506), respectively. The incidences of complication in non-operative group and in surgical intervention group were 27.8% (65/234) and 30.9% (84/272), respectively (P > 0.05). The mortality in non-operative group and in surgical intervention group were 9.4% (22/234) and 11.0% (30/272), respectively (P > 0.05). The curative rates in non-operative group and in surgical intervention group were 90.6% (212/234) and 85.7% (233/272), respectively (P > 0.05). CONCLUSIONS: Patients should be treated in ICU in the early phase of the disease when APACHE II score > 10. Pancreatic specialized and multidisciplinary team treatment, appropriate choice of timing, indication and procedure of surgical intervention and details of drainage are vital to the prognosis of SAP.

[Protection of CSE/H2S system in hepatic ischemia reperfusion injury in rats].

OBJECTIVE: To study the protective function and pathophysiology of cystathionine gamma-lyase (CSE)/hydrogen sulfide (H(2)S) system in hepatic ischemia-reperfusion injury (HIRI) in rats. METHODS: Wistar rats were randomly distributed into sham group (n = 18), ischemia-reperfusion (IR) group (n = 18), IR + NaHS group (n = 18) and IR + DL-propargylglycine (PAG) group (n = 18). The hepatic IR model was established by Pringle's hepatic vascular occlusion. At each of the indicated time points (1, 3 and 6 hours after IR), the serum levels of H(2)S and the hepatic CSE activity were measured. The serum levels of inflammatory factors, including TNF-α, IL-10 were determined by ELISA methods. The expression of apoptotic protein, TNF-α, in liver tissue was tested by Western blot assay, cell apoptosis was examined by TUNEL and the histological changes were examined in each group. RESULTS: The serum levels of H(2)S and CSE activity were significantly increased in group IR compared with group sham at all indicated time points (P < 0.05). The serum level of inflammatory factors (P < 0.01) and the hepatic expression of TNF-α protein (P < 0.05) were elevated obviously in group IR than that in group sham. Administration of NaHS could reduce the production of inflammatory factors in serum (P < 0.01), inhibit hepatic protein expression of TNF-α (P < 0.05) and attenuate the liver histological scores of IR injury (P < 0.05), whereas PAG aggravated them. CONCLUSION: The endogenous CSE/H(2)S system maybe involved in the pathogenesis of hepatic IR injury, which suggests that CSE/H(2)S system can protect liver from IR injury in rats by intervening in inflammatory reaction, attenuating the injury severity and inhibiting expression of apoptotic protein TNF-α.