Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC pa     

Endoscopic tools for the diagnosis and evaluation of celiac disease

Celiac disease(CD)is an autoimmune disease of the small bowel induced by ingestion of wheat,rye and barley.Current guidelines indicate histological analysis on at least four duodenal biopsies as the only way to diagnose CD.These indications are based on the conception of the inability of standard endoscopy to make diagnosis of CD and/or to drive biopsy sampling.Over the last years,technology development of endoscopic devices has greatly ameliorated the accuracy of macroscopic evaluation of duodenal villous pattern,increasing the diagnostic power of endoscopy of CD.The aim of this paper is to review the new endoscopic tools and procedures proved to be useful in the diagnosis of CD,such as chromoendoscopy,Fujinon Intelligent Chromo Endoscopy,Narrow Band Imaging,Optical Coherence Tomography,Water-Immersion Technique,confocal laser endomicroscopy,high-resolution magnification endoscopy,capsule endoscopy and I-Scan technology.     

肠道微生态影响动脉粥样硬化发生发展的机制

动脉粥样硬化(AS)不仅是一种炎症性疾病,而且属于一种代谢性疾病。肠道微生态的改变可对AS的发生发展产生双面影响。一方面,肠道菌群紊乱可以通过影响机体的胆碱代谢、氧化应激、炎症反应等机制直接促进AS产生发展,此外,可通过导致AS危险因素肥胖、高脂血症、糖尿病等的产生这些间接机制促AS的进展。另一方面,益生菌及益生元的增加则可有效地降低肠道微生物内毒素产生、增强肠道屏障、减轻机体质量、缓解炎症反应、改善胰岛素抵抗,进而在AS的进展方面发挥重要作用。因此,合理调控机体肠道微生态环境成为AS防治的新型重要手段。     

Neoadjuvant radiotherapy for rectal cancer management

Thirty per cent of all colorectal tumours develop in the rectum.The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions.Most patients with early rectal cancer can be adequately managed by surgery alone.However,a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery.Neoadjuvant therapy involves a variety of options including radiotherapy,chemotherapy used alone or in combination.Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery.The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes,within an intact mesorectal package,in order to minimise local recurrence.It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties.Pre-operative staging including CT thorax,abdomen,pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential.Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy.While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure,which includes patients with nodal involvement,extramural venous invasion and threatened circumferential margin.The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer.     

Quality of life after laparoscopic vs open sphincter-preserving resection for rectal cancer

AIM: To compare quality of life (QoL) outcomes in Chinese patients after curative laparoscopic vs open surgery for rectal cancer. METHODS: Eligible Chinese patients with rectal cancer undergoing curative laparoscopic or open sphincterpreserving resection between July 2006 and July 2008 were enrolled in this prospective study. The QoL outcomes were assessed longitudinally using the validated Chinese versions of the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQCR38 questionnaires before surgery and at 4, 8, and 12 mo after surgery. The QoL scores at the different time points were compared between the laparoscopic and open groups. A higher score on a functional scale indicated better functioning, whereas a higher score on a symptom scale indicated a higher degree of symptoms.RESULTS: Seventy-four patients (49 laparoscopic and 25 open) were enrolled. The two groups of patients were comparable in terms of sociodemographic data, types of surgery, tumor staging, and baseline mean QoL scores. There was no significant decrease from baseline in global QoL for the laparoscopic group at different time points, whereas the global QoL was worse compared to baseline beginning at 4 mo but returned to baseline by 12 mo for the open group (P = 0.019, Friedman test). Compared to the open group, the laparoscopic group had significantly better physical (89.9±1.4 vs 79.2±3.7, P = 0.016), role (85.0±3.4 vs 63.3±6.9, P = 0.005), and cognitive (73.5±3.4 vs 50.7±6.2, P = 0.002) functioning at 8 mo, fewer micturition problems at 4-8 mo (4 mo: 32.3±4.7 vs 54.7±7.1, P = 0.011; 8 mo: 22.8±4.0 vs 40.7±6.9, P = 0.020), and fewer male sexual problems from 8 mo onward (20.0±8.5 vs 76.7±14.5, P = 0.013). At 12 mo after surgery, no significant differences were observed in any functional or symptom scale between the two groups, with the exception of male sexual problems, which remained worse in the open group (29.2±11.3 vs 80.0±9.7, P = 0.026). CONCLUSION: Laparoscopic sphincter-preserving resection for rec     

PNPLA3 I148M polymorphism and progressive liver disease

The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.     

Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis

Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infection and evaluate gastric cancer risk.In 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic gastritis.The Kyoto classification organized endoscopic findings related to H.pylori infection.The Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to 8.Atrophy,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer risk.Diffuse redness and regular arrangement of collecting venules are related to H.pylori infection status.In subjects without a history of H.pylori eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no H.pylori infection.A Kyoto classification score of 2 or more indicates H.pylori infection.Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.     

Totally laparoscopic left hepatectomy using the Torsional Ultrasonic Scalpel

Minimal invasive techniques have allowed for major surgical advances.We report our initial experience of performing total laparoscopic left hepatectomy(segmentsⅡ-Ⅳ)with the Lotus(laparoscopic operation by torsional ultrasound)Ultrasonic Scalpel.The perioperative and postoperative courses of the young female patient were uneventful and she is in a good general condition without complaints 18 mo after surgery.To the best of our knowledge,this is the first total laparoscopic hemihepatectomy to be performed in Greece,as well as the first laparoscopic liver resection using Lotus shears.     

Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency

The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.     

Post-translational modifications of hepatitis C viral proteins and their biological significance

Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV proteins are essential for proper protein function and regulation,thus,directly affecting viral life cycle and the generation of infectious virus particles.Cleavage of the HCV polyprotein by cellular and viral proteases into more than 10 proteins represents an early protein modification step after translation of the HCV positivestranded RNA genome.The key modifications include the regulated intramembranous proteolytic cleavage of core protein,disulfide bond formation of core,glycosylation of HCV envelope proteins E1 and E2,methylation of nonstructural protein 3(NS3),biotinylation of NS4A,ubiquitination of NS5B and phosphorylation of core and NS5B.Other modifications like ubiquitination of core and palmitoylation of core and NS4B proteins have been reported as well.For some modifications such as phosphorylation of NS3 and NS5A and acetylation of NS3,we have limited understanding of their effects on HCV replication and pathogenesis while the impact of other modifications is far from clear.In this review,we summarize the available information on PTMs of HCV proteins and discuss their relevance to HCV replication and pathogenesis.     

Endoscopic resection techniques for colorectal neoplasia:Current developments

Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.     

Efficacy of the vaccination in inflammatory bowel disease

Inflammatory bowel disease (IBD) is associated with conditions that may predispose to infections, such as the lack of an appropriate innate immune response to infectious agents, malnutrition, surgery, and immunosuppressive and biological drugs. Some of these infections may be preventable by vaccination. Therefore, for this particular patient population, the benefits of implementing a well-established immunization protocol in daily clinical practice are potentially even greater than for the general population. In recent years international consensus guidelines have been published, but in spite of theses recommendations, studies have shown that a significant number of patients with IBD remain inadequately immunized. Another important issue regarding immunization in this population is that vaccine efficacy among patients receiving immunosuppressive therapies has been variable. In a healthy population, a humoral immune response to hepatitis B vaccination (HBV) is expected in > 90%, whereas a much lower rate is achieved in the IBD patients. Immunosuppressive, anti-tumor necrosis factor therapy and disease activity have been implicated in the impaired efficacy of the vaccination. The serological response to HBV should be confirmed and patients with an inadequate response should receive a second full series of vaccine. Modified dosing regimens, including doubling the standard antigen dose, might increase the effectiveness. Response to influenza, pneumococcal and tetanus immunization is still not clear, as there are studies that show a normal response to the vaccination while others demonstrate a lack of efficacy. We pose a series of questions on the efficacy of the different vaccinations recommended for IBD patients and attempt to answer them using scientific evidence.     

Hydroxycitric acid does not promote inflammation or liver toxicity

Garcinia cambogia extract(GC)with its active component consisting of hydroxycitric acid(HCA)is widely utilized for weight loss.Various HCA salts are available,including calcium,magnesium,potassium and mixtures of these.Experimentally,these salts exhibit different properties with some,but not all,improving glucose tolerance and blood pressure.Recently,obesity-prone C57BL/6J mice were fed a high-fat diet(HFD,45 kcal%fat)with or without GC(1%,w/w)for 16 wk.The active arm reduced visceral fat,adipocyte size and serum glucose,yet purportedly also exhibited hepatic collagen accumulation,lipid peroxidation and increased mRNA levels of genes related to oxidative stress.The latter findings are at odds with a large body of animal and human studies that have been conducted on the safety and efficacy of HCA.This literature shows HCA to be protective against the liver toxicity associated with ethanol and dexamethasone administration,and to maintain serum aspartate aminotransferase,alanine aminotransferase and alkaline phosphatase at near normal levels.In both animal and clinical literature,elevated intakes of HCA per se have not led to signs of inflammation or hepatotoxicity.The compound has been found to reduce markers of inflammation in brain,intestines,kidney and serum.     

Endoscopic trans-esophageal submucosal tunneling surgery:A new therapeutic approach for diseases located around the aorta ventralis

AIM To assess the efficiency of endoscopic trans-esophageal submucosal tunneling surgery(EESTS) technique for diseases located around the aorta ventralis.METHODS Nine pigs were assigned to EESTs. The procedures were as follows: First, a long esophageal submucosal tunnel was established. Second, full-thickness myotomy was created. Third, an endoscope was entered into the abdominal cavity through a muscle incision and the endoscope was around the aorta ventralis. Eventually,celiac trunk ganglion neurolysis, partial hepatectomy and splenectomy, partial tissue resection in the area of the posterior peritoneum, and endoscopic submucosal dissection(ESD) combined with lymph node dissection were performed. The animals were given antibiotics for 5 d and necropsied 7 d after surgery.RESULTS In all surgeries, one pig died from intraperitoneal hemorrhage after doing partial splenectomy, while the other pigs were alive after successfully operating other surgeries. For surgery of celiac trunk ganglion damage, at necropsy, there was no exudation in the abdominal cavity. Regarding surgery of partial hepatectomy, the wound with part healing was observed in the left hepatic lobe, and no bleeding or obvious exudation was seen. In surgery of partial splenectomy, massive hemorrhage was observed on the splenic wound surface, and the metal clips could not stop bleeding. After surgery of retroperitoneal tissue resection, mild tissue adhesion was observed in the abdominal cavity of one animal, and another one suffered from severe infection. For surgery of ESD and lymph node dissection, a moderate tissue adhesion was observed.CONCLUSION EESTS is a feasible and safe technique for diseases located around the aorta ventralis.     

Sex modification of the association of the radial augmentation index and incident hypertension in a Chinese community-based population

BACKGROUND Arterial stiffness,as assessed by aortic ultrasound and pulse wave velocity,is associated with incident hypertension.However,there is still no consensus on whether the augmentation index(AI)affects new onset of hypertension.This study investigated the relationship of radial AI(r AI)and incident hypertension in a Chinese community-based population without hypertension at baseline.METHOD A total of 1,615 Chinese non-hypertensive participants from an atherosclerosis cohort in Beijing,China were included in our analysis.Baseline r AI normalized to heart rate of 75 beats/min(r AIp75)was obtained using HEM-9000 AI.New-onset hypertension was defined as blood pressure≥140/90 mm Hg or self-reported hypertension or taking anti-hypertensive medications at the follow up survey.Multivariate regression models were used to evaluate the impact of r AIp75 on the risk of new-onset hypertension.RESULTS After a mean 2.35-year follow-up,213(13.19%)participants developed incident hypertension.No significant relation between r AIp75 and incident hypertension was observed in the whole population after adjustment for possible confounders(adjusted odds ratio(OR)and 95%confidence interval(CI):1.09[0.95-1.27];P=0.2260).However,r AIp75 was significantly associated with incident hypertension in women,but not in men(adjusted OR and 95%CI:1.29[1.06-1.56],P=0.0113 for women;0.91[0.72-1.15],P=0.4244 for men;P for interaction=0.0133).CONCLUSIONS Sex modified the effect of the r AI on incident hypertension in a Chinese,community-based,non-hypertensive population.Screening of the r AI could be considered in women with a high risk of hypertension for the purpose of primary intervention.     

Lymph node staging in colorectal cancer:Old controversies and recent advances

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer.For affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis.In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging.These include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected.Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression.Outcome prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved nodes.Extracapsular invasion has been identified as additional prognostic factor.Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis.The clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.     

Is exon mutation analysis needed for adjuvant treatment of gastrointestinal stromal tumor?

Gastrointestinal stromal tumors(GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract,resulting from an activating mutation of stem cell factor receptor(KIT),and an activating mutation of the homologous platelet-derived growth factor receptor alpha(PDGFRA) kinase.Most GISTs(90%-95%) are KIT-positive.About 5% of GISTs are truly negative for KIT expression.GISTs have been documented to resistant conventional chemotherapeutics.Due to the KIT activation that occurs in the majority of the cases,KIT inhibition is the primary treatment approach in the adjuvant treatment of metastatic GISTs.Imatinib mesylate is an oral agent that is a selective protein tyrosine kinase inhibitor of the KIT protein tyrosine kinase,and it has demonstrated clinical benefit and objective tumor responses in most GIST patients in phase Ⅱ and Ⅲ trials.The presence and the type of KIT or PDGFRA mutation are predictive of response to imatinib therapy in patients with advanced and metastatic disease.Molecular analysis in phaseⅠ-Ⅱ trials revealed significant differences in objective response,progression-free survival,and overall survival between GISTs with different kinase mutations.The aim of this letter is to touch on the need for exon mutation analysis for adjuvant treatment with imatinib in GIST patients.     

Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study

AIM:To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease(AN-PEP)to mitigate the im-munogenic effects of gluten in celiac patients.METHODS:Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet(GFD)resulting in normalised antibodies and mucosal healing classified as Marsh 0 orⅠwere included.In a randomised double-blind placebo-controlled pilot study,patients consumed toast(approximately 7 g/d gluten)with AN-PEP for 2 wk(safety phase).After a 2-wk washout period with adherence of the usual GFD,14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk(efficacy phase).Measurements at baseline included complaints,quality-of-life,serum antibodies,immunophenotyping of T-cells and duodenal mucosa immunohistology.Furthermore,serum and quality of life questionnaires were collected during and after the safety,washout and efficacy phase.Duodenal biopsies were collected after the safety phase and after the efficacy phase.A change in histological evaluation according to the modified Marsh classification was the primary endpoint.RESULTS:In total,16 adults were enrolled in the study.No serious adverse events occurred during the trial and no patients withdrew during the trial.The mean score for the gastrointestinal subcategory of the celiac disease quality(CDQ)was relatively high throughout the study,indicating that AN-PEP was well tolerated.In the efficacy phase,the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed.During the efficacy phase,neither the placebo nor the AN-PEP group developed significant antibody titers.The IgA-EM concentrations remained negative in both groups.Two patients were excluded from entering the efficacy phase as their mucosa showed an increase oftwo Marsh steps after the safety phase,yet with undetectable s     

Prophylactic drains in totally laparoscopic distal gastrectomy:are they always necessary?

Prophylactic drains have always been a useful tool to detect early complications and prevent postoperative fluid collections,particularly in gastrointestinal surgery.Recently,the utilization of such drains has been debated,due to mounting evidence that they could be harmful rather than beneficial.Based on recent published articles,Liu et al reported that the routine use of prophylactic drains in total laparoscopic distal gastrectomy might not be necessary for all patients.Herein,we express our opinion regarding this interesting publication.     

1-磷酸鞘胺醇受体3参与巨噬细胞迁移及脓毒症诱导的心肌损伤

目的探讨巨噬细胞中1-磷酸鞘胺醇受体(sphingosine 1-phosphate receptor,S1PR)的表达及其作用,观察干预S1PR3(S1P3)对脂多糖诱导的心肌损伤的影响。方法传代培养小鼠Ana-1巨噬细胞,给予脂多糖(lipopolysaccharide,LPS,100 ng/ml)刺激或S1P3特异性抑制剂CAY-10444(10μmol/L)干预,细胞随机分为对照组、LPS组、CAY-10444组、CAY-10444预处理2h+LPS组,Transwell小室观测巨噬细胞迁移,蛋白免疫印迹检测巨噬细胞S1PR的表达,并检测p-Akt/Akt蛋白水平。在体实验,6~8周龄雄性C57/B6小鼠,随机分为对照组、LPS组、CAY-10444组、CAY-10444干预+LPS组,每组12只,LPS(10 mg/kg)腹腔注射,或CAY-10444 1 mg/kg于LPS诱导后30 min腹腔注射干预,24 h后取心脏组织HE染色观察病理改变,免疫组化染色观察巨噬细胞浸润程度以及炎症因子的表达情况,实时荧光定量PCR检测心肌损伤标记分子BNP、巨噬细胞表面分子F4/80、炎症因子TNF-α、IL-1β、IL-6的mRNA水平。结果与对照组比较,LPS诱导巨噬细胞大量迁移S1P3蛋白表达增加(P0.01),p-Akt Ser473/Akt表达上调(P0.01);与LPS组相比,S1P3抑制剂CAY-10444干预后再给予LPS刺激,巨噬细胞迁移被抑制(P0.01),p-Akt Ser473/Akt表达也降低(P0.01);在体实验,LPS诱导小鼠后BNP mRNA水平明显上调(P0.01),同时F4/80以及炎症因子TNF-α、IL-1β、IL-6的mRNA水平上调(P0.01),HE染色可见心肌损伤及炎细胞浸润,免疫组化染色法显示F4/80及炎症因子的大量阳性表达(P0.01);使用S1P3抑制剂后,与LPS组比较,心肌损伤减轻免疫组化中巨噬细胞减少(P0.01),炎症因子表达降低(P0.01),BNP mRNA水平降低(P0.01),F4/80以及TNF-α、IL-1β、IL-6的mRNA水平也明显降低(P0.01)。结论抑制巨噬细胞S1P3表达可抑制巨噬细胞的迁移并提示p-Akt/Akt与了这一过程,此外,S1P3抑制剂的干预可有效减轻LPS诱导的心肌损伤。