Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.

MRI shows clodronate-liposomes attenuating liver injury in rats with severe acute pancreatitis

BACKGROUND: Studies have revealed that macrophages play an important role in the development of severe acute pancreatitis (SAP). Activated macrophages can lead to a systemic inflammatory response, induce lipid peroxidation, impair membrane structure, result in injury to the liver and the other extrahepatic organs, and eventually result in multiple organ dysfunction syndrome by promoting excessive secretion of cytokines. Liver injury can further aggravate the systemic inflammatory response and increase mortality by affecting the metabolism of toxins and the release of excessive inflammatory mediators. Clodronate is a synthetic bisphosphonate, which is often used for treating bone changes caused by osteoporosis and other factors. In the current study, we created liposomes containing superparamagnetic iron oxide particles (SPIOs) for macrophage labeling and magnetic resonance imaging, using a novel method that can bind the clodronate to induce apoptosis and deplete macrophages. METHODS: Superparamagnetic Fe(3)O(4) nanoparticles were prepared by chemical coprecipitation. SPIO-containing liposomes and SPIO-clodronate-containing liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate (2 ml/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group, a SAP plus SPIO-liposome group, and a SAP plus SPIO-clodronate-containing group. Two and six hours after SAP models were available, T2-weighted MRI scans (in the same plane) of the livers of rats in each group were performed. At the end of the scans, 2 ml of blood was taken from the superior mesenteric vein to measure the levels of serum amylase, ALT, AST, TNF-alpha, and IL-6. Pathological changes in the liver and pancreas were assessed. RESULTS: Transmission electron microscopy showed that the liposomes had a uniform size. No pathological changes in the pancreata of rats in the control group were noted. The pathological changes in the pancreata and livers of rats in the SAP plus SPIO-clodronate-containing liposome group were milder than those in the SAP plus SPIO-liposome group. The MRI signal intensity of the livers in the SAP plus SPIO-liposome and SAP plus SPIO-clodronate-containing groups was significantly lower than that in the control group. There were significant changes in the two experimental groups (P<0.01). In addition, the levels of serum amylase, ALT, AST, TNF-alpha, and IL-6 in rats in the SAP plus SPIO-liposome group were higher than those in the control group (P<0.01), while the corresponding levels in the SPIO-clodronate-containing liposome group were significantly lower than those in the SAP plus SPIO-liposome group (P<0.01). CONCLUSION: Clodronate-containing liposomes protect against liver injury in SAP rats, and SPIO can be used as a tracer for MRI examination following liver injury in SAP rats. (Hepatobiliary Pancreat Dis Int 2010; 9: 192-200)

Liver injury associated with acute pancreatitis:The current status of clinical evaluation and involved mechanisms

Acute pancreatitis(AP)is a very common acute disease,and the mortality rate of severe AP(SAP)is between 15%and 35%.The main causes of death are multiple organ dysfunction syndrome and infections.The mortality rate of patients with SAP related to liver failure is as high as 83%,and approximately 5%of the SAP patients have fulminant liver failure.Liver function is closely related to the progression and prognosis of AP.In this review,we aim to elaborate on the clinical manifestations and mechanism of liver injury in patients with AP.

Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis

AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloeemodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-a and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Protection effect of triptoKde to Kver injury in rats with severe acute pancreatitis

BACKGROUND: The high mortality of patients with severe acute pancreatitis (SAP) is due to multiorgan dysfunction. The mechanisms of SAP are still obscure. The aim of this study was to investigate the role of nuclear factor-kappa B (NF-κB) activation in rats with SAP associated with liver injury and the protection effect of triptolide against liver injury in rats with SAP. METHODS: Ninety Wistar rats were randomly divided into three groups (n =30 each group) : severe acute pancreatitis (group P) , treatment with triptolide ( group T), and sham operation (group S). SAP models were induced by retrograde injection of 5% sodium taurocholate to the pancreatic duct. After the model was successfully established, no treatment was given to group P. In group T, triptolide (0. 05 mg/ml) was injected intraperitoneally (0.2 mg/kg). In group S, the abdominal walls of rats were opened, sutured , but not treated. The rats -were sacrificed after operation at 2, 6, and 12 hours, respectively. The serum levels of amylase (AMY) , alanine aminotransferase (ALT), tumor necrosis factor-alpha ( TNF-α) and interleukin-6 (IL-6 ) were determined at three time points (10 rats for each time point). Liver tissues were obtained to detect the activity of NF-κB and to observe their pathological changes with light and electron microscopes. RESULTS: The serum levels of AMY and ALT were higher in groups P and T than in group S. The serum AMY levels were significantly lower in group T than in group P at 12 hours after operation. The serum ALT levels were significantly lower in group T than in group P at 6, 12 hours after operation. At the three time points, the levels of TNF-α and IL-6 in groups P and T increased more significantly than in group S. In group T they were decreased more significantly than in group P at the three time points. In groups P and T, NF-κB activity in liver tissue increased more significantly than in group S at the three time points. The activity of NF-κB was higher in group P than in groups S and T at the three time points. Liver pathological damages were milder in group T than in group P under light and electron microscopes. CONCLUSIONS: NF-κB plays an important role in the pathogenesis of liver injury in rats with SAP. Triptolide can reduce pathological damage to the liver. Its mechanism is to inhibit the activity of NF-κB and to decrease the release of inflammatory mediators.

Therapeutic effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis

Objective: To assess the therapeutic effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis (SAP). Methods: Forty-two SD rats were randomly divided into 3 groups: healthy controls (HC, n=6); SAP-S group (n=18); SAP-ICE-I group (n=18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bili-pancreatic duct in SD rats. HC rats underwent same surgical procedures and duct cannulation without sodium taurocholate. In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis, which was repeated after 12 h. In SAP-ICE-I group, rats were firstly given ICE inhibitor intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, this was repeated at 12 h. Survied rats were killed at certain time points, and all samples were obtained for subsequent analysis. Results: The serum levels of ALT, AST and IL-1β in SAP-S group were (215.50±58.52)U/L, (372.17±38.05)U/L, (276.77±44.92)pg/ml at 6 h, (396.67±70.29)U/L, (548.50±75.29)U/L, (308.99±34.95)pg/ml at 12 h, (425.17±86.33)U/L, (665.83±84.05)U/L, (311.60±46.51)pg/ml, respectively, which were increased significantly (P<0.01, vs HC). In SAP-ICE-I group, their levels were decreased significantly (P<0.01, vs SAP-S). Intrahepatic expressions of Caspase-1, IL-1β and IL-18 mRNA could be observed in HC, which were increased significantly in SAP-S group (P<0.01, vs HC). The expressions of IL-1β and IL-18 mRNA were decreased significantly in SAP-ICE-I group (P<0.01, vs SAP-S), whereas Caspase-1 mRNA expressions had no significant differences (P>0.05). Caspase-1 inhibition had no effect on the severity of liver tissue damage. Conclusion: Caspase-1 activate cytokines, IL-1β and IL-18, play a pivotal role in the course of liver injury in SAP. Caspase-1 inhibitor can improve liver functions effectively.

异甘草酸镁结合柴芩承气汤对重症急性胰腺炎伴肝损伤的疗效

目的探讨异甘草酸镁结合柴芩承气汤治疗重症急性胰腺炎(SAP)伴肝损伤患者的临床效果。方法将我院2022年1月至2023年6月收治的92例SAP伴肝损伤患者随机分为两组各46例。对照组采用异甘草酸镁治疗,观察组在此基础上采用柴芩承气汤治疗,对比两组的恢复相关指标、胰腺功能、肝功能和炎性因子水平。结果观察组腹痛缓解时间、血清淀粉酶恢复时间及住院时间短于对照组(P<0.05)。治疗后,观察组血清淀粉酶、血尿淀粉酶、脂肪酶、ALT、AST、γ-GT、IL-6、NF-κB、TNF-α水平低于对照组,ALB水平高于对照组(P<0.05)。治疗期间,两组均未发生严重不良反应。结论异甘草酸镁结合柴芩承气汤可改善SAP伴肝损伤患者的胰腺功能和肝功能,降低外周血中性粒细胞中NF-κB水平。

血清淀粉酶及肝损伤相关指标在急性胰腺炎病情评估中的应用

目的 探究血清淀粉酶及肝损伤相关指标在急性胰腺炎(AP)病情评估中的应用价值。方法 选择2020年3月至2022年4月首都医科大学附属北京世纪坛医院收治的AP患者112例,根据病情状况分为轻症AP(MAP)组(n=62)、中度重症AP(MSAP)组(n=36)、重症AP(SAP)组(n=14),入院时均检测血清淀粉酶、肝损伤相关指标[白蛋白(ALB)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)]水平,分析各指标评估SAP的效能。结果 三组血清淀粉酶水平比较差异无统计学意义(P>0.05),ALB:MAP组>MASP组>SAP组,ALT、AST、TBil:MAP组0.05;ALB水平与病情严重程度负相关(r=-0.446,P<0.05);ALT、AST、TBil水平与病情严重程度正相关(r=0.757,0.588,0.584,P<0.05);肝损伤指标联合预测SAP的ROC曲线下面积为0.970(95%CI:0.919~0.993),敏感度、特异度均为92.86%,预测效能较单项指标提高。结论 血清淀粉酶与AP病情严重程度无关,ALB、ALT、AST、TBil水平均与AP病情严重程度相关,可用于预测SAP。

高甘油三酯血症性重症急性胰腺炎并发急性肝损伤的危险因素分析

目的探讨高甘油三酯血症性重症急性胰腺炎(HTC-SAP)并发急性肝损伤(ALI)的危险因素。方法回顾性分析2013年1月至2022年9月安徽医科大学第二附属医院重症医学一科收治的120例HTG-SAP患者的临床资料。根据有无并发急性肝损伤分为ALI组(n=55),非ALI组(n=65)。比较两组患者的一般资料及实验室指标,将两组间存在统计学差异的实验室指标全部纳人多因素二元logistic回归分析,探究HTG SAP并发ALI的独立危险因素。结果120例HTG-SAP患者中并发ALI者55例(45.83%)、非ALI者65例(54.17%)。与非ALI组患者相比,ALI组患者急性生理与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、序贯器官衰竭评分(SOFA)评分及白细胞介素-6(IL-6)(196.00(118.30,549.40))、甘油三酯(TG)(16.53±10.43)、乳酸脱氢酶(LDH)(611.00(415.00,1240.00))、凝血酶原时间(PT)(14.05±2.93)水平均明显更高,血小板计数(PLT)(161.75±70.73)水平则明显更低(均P<0.05),且ALI组既往有糖尿病病史的比例(24(43.64%))明显高于非ALI组(P<0.05)。Logistic回归分析显示:TG(OR=1.060)、LDH(OR=1.002)、PLT(OR=0.992)、有无糖尿病(OR=2.989)均是HTG-SAP患者并发ALI的独立影响因素(均P<0.05)。结论TG、LDH、PLT、既往有无糖尿病病史均为HTG-SAP并发ALI的独立影响险因素,HTG-SAP并发ALI是导致病死率增高的主要原因之一。

腹腔穿刺引流对重症急性胰腺炎大鼠相关肝损伤的保护作用

目的:探讨腹腔穿刺引流(APD)对重症急性胰腺炎(SAP)大鼠相关肝损伤的影响。方法:将30只SD大鼠随机分为SAP未处理组(SAP组)、SAP APD组(APD组)和假手术组(SHAM组),每组10只。通过应用牛磺胆酸钠诱导重症急性胰腺炎模型,利用ELISA法检测大鼠外周血中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6及IL-10表达量;利用Western blotting法检测肝组织中Toll样受体4(TLR4)、磷酸化NF-κB抑制蛋白(p-IκB)、白细胞介素-1受体相关激酶4(IRAK-4)、磷酸化肿瘤坏死因子受体相关因子6(TRAF6)和核转录因子-κB(NF-κB)p65的蛋白表达水平;在光镜下对肝组织进行形态学观察。结果:肝组织病理学结果显示APD组肝组织损伤程度轻于SAP组而重于SHAM组;在外周血中,与SHAM组比较,APD组TNF-α、IL-6、IL-10的表达水平均明显升高(P<0.01);与SAP组比较,APD组TNF-α、TL-6的表达水平降低(P<0.01),IL-10表达水平明显升高(P<0.01)。在肝组织中,与SHAM组比较,APD组TLR4、p-IκB、IRAK-4、TRAF6和NF-κB p65蛋白表达水平均明显升高(P<0.01);与SAP组比较,APD组TLR4蛋白表达水平均明显降低(P<0.01)。结论:SAP合并肝损伤大鼠早期应用APD治疗可减轻肝细胞损伤,且APD抑制SAP大鼠肝损伤可能通过抑制TLR4/NF-κB信号通路表达来实现。

重症急性胰腺炎患者外周血TLR4、TRAF6的表达及与并发肝损伤的关系

目的探讨Toll样受体4(TLR4)、肿瘤坏死因子受体相关因子6(TRAF6)水平在重症急性胰腺炎(SAP)外周血中的表达及与并发肝损伤的关系。方法选取2018年10月—2021年10月厦门长庚医院收治的187例SAP患者,依据是否发生肝损伤分为肝损伤组和无肝损伤组。对比肝损伤组和无肝损伤组临床资料、TLR4和TRAF6 mRNA相对表达量。采用多因素Logistic逐步回归模型分析SAP患者发生肝损伤的相关因素。绘制受试者工作特征(ROC)曲线,分析外周血TLR4 mRNA、TRAF6 mRNA及两者联合检测对SAP患者肝损伤发生的预测价值。结果187例SAP患者并发肝损伤62例,未并发肝损伤125例。肝损伤组急性胰腺炎床旁严重度指数(BISAP)评分、脂肪酶、淀粉酶(AMY)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)、TLR4 mRNA、TRAF6 mRNA相对表达量高于无肝损伤组(P<0.05)。多因素Logistic逐步回归分析结果显示:BISAP评分[OR=2.892(95%CI:1.482,5.645)]、TLR4 mRNA[O^R=3.334(95%CI:1.710,6.512)]、TRAF6 mRNA[O^R=3.059(95%CI:1.567,5.970)]均为影响SAP患者肝损伤发生的危险因素(P<0.05)。ROC曲线分析结果显示,外周血TLR4 mRNA、TRAF6 mRNA及两者联合预测SAP患者肝损伤发生的敏感性分别为80.65%(95%CI:0.621,0.872)、77.42%(95%CI:0.546,0.824)、75.81%(95%CI:0.534,0.819),特异性分别为73.60%(95%CI:0.503,0.796)、80.80%(95%CI:0.617,0.863)、99.20%(95%CI:0.725,0.998),曲线下面积分别为0.792(95%CI:0.727,0.848)、0.824(95%CI:0.762,0.876)、0.856(95%CI:0.797,0.903)。结论外周血TLR4、TRAF6表达均与SAP患者并发肝损伤有关,且外周血TLR4 mRNA、TRAF6 mRNA联合检测对SAP患者发生肝损伤的预测效能较高。

红细胞压积差值、红细胞分布宽度与白蛋白比值联合炎性指标对急性胰腺炎病情严重程度及合并肝损伤风险的临床预测价值

目的探讨分析红细胞压积差值(HCT^(*))、红细胞分布宽度与白蛋白比值(RDW/ALB)及炎性指标(白细胞WBC、中性粒细胞与单核细胞比值NMR、中性粒细胞与淋巴细胞比值NLR、淋巴细胞与单核细胞比值LMR、降钙素原PCT)对急性胰腺炎(AP)患者病情严重程度及合并肝损伤风险的预测价值。方法回顾性收集2019年4月至2022年12月于西南医科大学附属医院消化内科住院的225例AP病人的一般信息及入院72小时内实验室指标,所有病例按病情严重程度将分为轻症组(轻度急性胰腺炎MAP)123例及重症组(SAP包括中至重度急性胰腺炎)102例,根据有无肝损伤分为肝损伤组89例及无肝损伤组136例,单因素分析比较不同病情患者临床信息,ROC曲线分析比较HCT^(*)、RDW/ALB及上述炎性指标对AP患者病情严重程度及合并肝损伤风险的临床预测价值。结果轻症组与重症组AP患者在性别、年龄、病因、合并症、吸烟史、饮酒史、NMR、AST、ALT、GGT、ALP、TBIL、TG、TC等方面差异无统计学意义(P>0.05),重症组患者住院天数、HCT^(*)、RDW/ALB及白细胞计数、中性粒细胞计数、单核细胞计数、NLR、LMR、PCT、等高于轻症组(P<0.05);肝损伤组住院时长、RDW/ALB、TG及白细胞计数、NMR、NLR、PCT等均高于无肝损伤组(P<0.05),两组在LMR、TC等方面差异无统计学意义(P>0.05);ROC曲线预测AP病情严重程度时WBC的曲线下面积最大,AUC为0.621,预测效应最强,LMR的敏感性最高为66.6%,HCT^(*)特异性最高为74.8%,所有炎性指标联合起来的预测效应大于单独单个炎性指标,将所有有意义指标联合进行AP病情预测时预测效应达到最大,AUC达0.756;在预测AP合并肝损伤时单个指标中WBC的曲线下面积最大为0.652,预测效应最强,特异度也最高为74.3%,RDW/ALB敏感度最高为76.2%,炎性指标联合预测AP合并肝损伤的总效应大于单个指标,而HCT^(*)、RDW/ALB及所有有意义的炎性指标联合诊断AP合并肝损伤的效应最大,此时曲线下面积为0.739,敏感度及特异度均高,有较大的预测价值。结论HCT^(*)、RDW/ALB及炎性指标WBC、NLR、LMR、PCT对AP病情严重程度具有较好的预测价值,而HCT^(*)、RDW/ALB及炎性指标WBC、NMR、NLR、PCT则对AP合并肝损伤具有较好的预测价值,分别联合上述指标可对患者病情进行合理有效评估,对临床具有重要价值。

急性胰腺炎肝脏损伤的表现及其发病机制的研究进展

急性胰腺炎常累及肝、肺及肾脏等远处器官,尽管急性胰腺炎时肝脏损伤多较轻,但对终末期肝功能衰竭目前尚无 好的治疗方法。本文综述了急性胰腺炎肝脏损伤的表现及发病机制,旨在进一步理解急性胰腺炎时全身炎症反应和多器官衰 竭的机制,为探索其防治措施提供新的思路。

柴芩承气汤对重症急性胰腺炎并肝损伤大鼠肝组织氧化应激的影响

目的探讨柴芩承气汤对重症急性胰腺炎(SAP)并肝损伤大鼠肝组织氧化应激的影响。方法 72只Sprague Dawley大鼠随机分为假手术组、模型组和观察组,每组24只,各组再随机分为1、5、10 h 3个亚组,每组8只,假手术组大鼠打开腹腔后仅翻动胰腺组织数次,不给予任何干预;模型组和观察组大鼠采用去氧胆酸钠逆行胰胆管注射建立SAP大鼠模型。假手术组和模型组大鼠在造模成功后,1 h亚组在术后1 h,5 h亚组在术后1、5 h,10 h亚组在术后1、5、10 h,分别按10 m L·kg-1给予生理盐水灌胃1次;观察组1 h亚组大鼠在术后1 h,5 h亚组大鼠在术后1、5 h,10 h亚组大鼠在术后1、5、10 h,分别按10 m L·kg-1给予1 000 g·L-1柴芩承气汤灌胃1次。假手术组、模型组和观察组各亚组大鼠分别在末次灌胃后4 h麻醉处死大鼠,下腔静脉取血用于血清淀粉酶(AMS)检测;取胰腺组织和肝脏组织,用体积分数10%中性甲醛溶液固定,苏木精-伊红染色进行病理学观察;部分肝组织制备匀浆,进行超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)检测。结果假手术组1、5、10 h亚组大鼠胰腺组织结构清晰,腺泡小叶完整。模型组1 h亚组大鼠胰腺组织小叶间质水肿,可见大量炎性细胞浸润;5 h亚组大鼠胰腺组织水肿进一步增加,出血坏死、炎性细胞浸润明显;10 h亚组大鼠胰腺组织出现大面积腺泡细胞坏死。观察组1、5、10 h亚组大鼠胰腺损伤均明显减轻,仅见胰腺间质水肿和少量炎细胞浸润,坏死面积明显减少。假手术组1、5、10 h亚组大鼠肝细胞排列整齐,细胞质均匀,肝小叶及小叶中央静脉完整,轮廓清楚,肝细胞索网状纤维结构完整。模型组1、5 h亚组大鼠肝小叶界限不清,肝细胞索紊乱,肝窦变窄,肝细胞点状坏死和炎细胞浸润;10 h亚组大鼠可见大片肝细胞坏死。观察组1、5、10 h亚组大鼠肝细胞的水肿、炎症反应均有所减轻,肝小叶仅见少量炎症细胞浸润,未见明显坏死。与假手术组大鼠比较,模型组1、5、10 h亚组大鼠血清AMS水平均显著升高(P<0.05);与模型组大鼠比较,观察组1、5、10 h亚组大鼠血清AMS水平均显著下降(P<0.05);与假手术组大鼠比较,模型组1、5、10 h亚组大鼠肝组织SOD活性均显著下降(P<0.05),MDA含量、MPO活性均显著升高(P<0.05);与模型组大鼠比较,观察组1、5、10 h亚组大鼠肝组织SOD活性均显著升高(P<0.05),MDA含量、MPO活性均显著下降(P<0.05)。结论柴芩承气汤通过抑制氧化应激减轻胰腺、肝脏损害,对大鼠SAP合并肝脏损伤发挥治疗作用。

柴芩承气汤通过抑制TLR4/NF-κB p65通路减轻小鼠重症急性胰腺炎并发肝损伤

目的基于TLR4/NF-κB p65信号通路探讨柴芩承气汤(chaiqinchengqi decoction,CQCQD)对小鼠重症急性胰腺炎(severe acute pancreatitis,SAP)并发肝损伤的保护机制。方法昆明小鼠36只,随机分为3组(n=12),即对照组(Control),重症急性胰腺炎模型组(SAP)和柴芩承气汤治疗组(SAP+CQCQD)。腹腔注射20%L-精氨酸(3.3 g·kg-1,2次,间隔1 h)建立SAP模型,治疗组给予柴芩承气汤灌胃(19 g·kg-1·d-1)。造模后72 h观察胰腺、肝脏组织病理变化,检测血清内毒素含量,肝组织TLR4、p-NF-κB p65蛋白表达,及肝内炎性因子水平。结果与Control组相比,SAP组胰腺和肝脏可见明显的病理损伤,血清内毒素含量增多,肝组织TLR4、p-NF-κB p65表达增加,IL-6、TNF-α、MIP-1αmRNA水平升高。与SAP组相比,柴芩承气汤组胰腺和肝脏组织病理损伤减轻,血清内毒素含量降低,肝组织TLR4、p-NF-κB p65表达和IL-6、TNF-α、MIP-1α mRNA水平减少。 结论 柴芩承气汤可能通过抑制肝组织TLR4/NF-κB p65通路活化,降低促炎因子水平,从而减轻小鼠SAP并发肝损伤。

急性胰腺炎肝巨噬细胞表达的FasL在肝损伤中的作用

目的:探讨肝巨噬细胞表达的Fas配体(FasL)在实验性急性胰腺炎(AP)肝损伤中的作用。方法:建立AP小鼠模型。雄性ICR小鼠30只,随机分为5组,每组6只,其中一组为对照组,腹腔注射0.1m l等渗盐水,4 h后心脏穿刺抽血,并处死小鼠留取标本;另4组均腹腔注射雨蛙素50μg/kg,每4 h注射1次至24 h,分别在4、8、16和24 h心脏穿刺抽血,并处死小鼠留取标本。用自动化生化仪检测血清ALT、AST、LDH和AMY的浓度,用ELISA试剂盒检测血清FasL浓度,用W estern b lot检测肝FasL蛋白的表达。结果:雨蛙素诱导的小鼠AP组与对照组相比,各个检测时间点血清AST、ALT、LDH、AMY水平明显增加。在4、8、16和24 h时AP组血清FasL浓度为(532.17±46.92)、(496.73±32.62)、(485.57±18.31)和(448.08±26.44)pg/m l,均显著高于对照组(80.34±6.81)pg/m l,AP组各检测时间点肝FasL蛋白表达也增加,与对照组相比,差异有显著统计学意义(P<0.01)。结论:AP通过上调肝巨噬细胞表达的FasL介导肝损伤。

JAK/STAT信号通路在胰弹性蛋白酶诱导大鼠Kupffer细胞分泌IL-18中的作用

目的:探讨JAK/STAT信号通路在胰弹性蛋白酶(elastase)诱导Kupffer细胞分泌IL-18中的作用机制.方法:采用酶消化法及密度梯度离心法将提取的肝脏Kupffer细胞分为4组,A组:生理盐水组(正常对照组);B组:脂多糖(LPS)处理组;C组:LPS和elastase处理组;D组:AG490预处理组.采用酶免疫吸附(ELISA)法检测Kupffer细胞上清液中IL-18含量;细胞免疫荧光染色技术和Western blot法检测细胞总蛋白中JAK2的表达.结果:与A组比较,B组在给予LPS刺激后,JAK2蛋白的表达以及上清液中IL-18含量均明显增加(IL-18:312.23±20.5ng/Lvs13.50±2.18ng/L,P<0.01);C组在同时给予LPS和elastase刺激后,JAK2的表达显著升高,上清液中IL-18含量与B组比较也显著增加(P<0.01);而D组在预先给予AG490处理后,JAK2表达明显下降,上清液中IL-18含量也有不同程度降低,与C组比较差异有统计学意义(317.31±25.24ng/Lvs438.86±21.32ng/L,P<0.01),但与B组比较,各值仅有轻微变化,差异无统计学意义.结论:抑制JAK/STAT通路的活化可下调elastase诱导Kupffer细胞分泌促炎症因子IL-18的表达,这可能有助于减轻急性胰腺炎时炎症反应和肝损伤.

急性胰腺炎合并肝脏损伤的CT、超声影像诊断价值

目的对比分析急性胰腺炎合并肝脏损伤的CT、超声表现,明确肝损伤的病因。方法选用临床确诊的急性胰腺炎患者28例,筛选其中21例CT表现为肝脏密度减低者作为研究对象,然后进行治疗前后CT、超声对比综合观察分析。选用GE128层宝石能谱CT,重建层厚为0.625 mm,全部病例同时进行能谱扫描并重建能谱曲线,16例患者治疗前行增强扫描。结果 21例患者肝脏密度减低者,能谱曲线均与脂肪曲线相似;21例患者同时行超声检查,均符合脂肪肝回声增强表现,吻合率100%。治疗后复查CT 5例肝脏密度不同程度回升但未完全恢复正常,11例患者完全恢复正常,5例患者无明显改变,超声显示14例患者同步回声减弱或恢复正常,7例患者未见明显变化。结论 CT能谱曲线结合超声检查诊断急性胰腺炎合并肝脏损伤的病因为脂肪浸润所致急性脂肪肝。

核因子-κB在重症急性胰腺炎肝损伤中的作用研究

目的 探讨核因子 κB(nuclearfactor kappaB ,NF κB)在重症急性胰腺炎 (SAP)肝损伤发病机制中的作用。方法 38只健康雌性Wistar大鼠随机分为SAP组 ,PDTC(二硫代氨基甲酸吡咯烷 )预处理组及正常组3组。SAP模型经胆胰管内加压注射 5 %牛磺胆酸钠溶液 0 .1ml/10 0 g完成。PDTC预处理组在建立SAP模型前 1h腹腔内按 10 0mg/kg体重注入PDTC。建模后 3、6、12h 3个时间点将大鼠处死 ,血样检测天冬氨酸转氨酶 (AST) ,留取肝组织苏木精 伊红染色下观察肝组织受损情况 ,应用SP免疫组化法检测SAP肝组织NF κB ,用RT PCR的方法检测肿瘤坏死因子 α(TNF α)、白介素 6 (IL 6 )、细胞间粘附分子 1(ICAM 1)mRNA的表达。结果 SAP肝组织苏木精 伊红染色未见明显的肝细胞坏死和肝细胞凋亡出现。PDTC预处理组与未处理组未见差别。SAP组AST明显升高 ,与正常组相比有显著性差异 ,PDTC预处理后各时间点AST均较未处理组下降。正常肝组织偶见NF κB活化的肝细胞 ,在SAP肝组织可见肝细胞NF κB活化。经PDTC预处理后肝组织NF κB活化的阳性肝细胞数与未经PDTC处理者相比明显减少。SAP时肝组织TNF α、IL 6、ICAM 1mRNA的表达明显增加 ,经PDTC预处理后相应各时间点均降低。但SAP肝组织ICAM 1mRNA各时间点均无明显改变。结?

急性胰腺炎并发肝损害的临床分析

目的:急性胰腺炎常并发胰外器官损害,肝是其常累及的器官,肝损害会恶化病情。文中探讨急性胰腺炎(AP)并发肝损害的临床特征。方法:利用医院病案检索系统随机检索病例156例对AP合并肝损害的102例患者进行分析,共分为2组:重症AP(SPA)组,44例;轻症AP(MAP)组58例。比较2组患者肝损害程度及病情恢复情况。结果:半数以上的AP患者发生肝损害,与轻度AP相比,其肝损害更严重、肝功能恢复更慢、病程更长。结论:AP肝损害的发生率及损害程度与胰腺炎严重程度呈正相关。