两种不同手术方式治疗恶性梗阻性黄疸患者的临床疗效比较研究

目的:探讨经皮肝穿刺胆管引流术(PTCD)与经内镜逆行胰胆管造影术(ERCP)治疗恶性梗阻性黄疸的治疗效果,并进行比较分析。方法:选取2016年1月~2018年5月期间我院收治的127例恶性梗阻性黄疸患者。根据治疗术式的不同将患者分为ERCP组(n=63,采用ERCP联合金属支架置入术进行治疗)和PTCD组(n=64,采用PTCD进行治疗),比较两组患者术后5d黄疸缓解率,比较两组患者术前、术后2周肝功能指标[血清总胆红素(TBIL)、丙氨酸转氨酶(ALT)、直接胆红素(DBIL)],比较两组患者术后舒适度量表评分情况及并发症发生情况。结果:两组患者术后黄疸总缓解率比较差异无统计学意义(P0.05);PTCD组低位梗阻患者黄疸缓解率低于ERCP组,而高位梗阻患者黄疸缓解率高于ERCP组(P0.05)。两组患者术前、术后2周TBIL、ALT、DBIL比较差异无统计学意义(P0.05);两组患者术后2周TBIL、ALT、DBIL水平较术前比较均下降(P0.05)。ERCP组患者术后舒适度量表评分总分低于PTCD组,差异有统计学意义(P0.05)。PTCD组术后并发症总发生率14.06%(9/64),低于ERCP组的41.27%(26/63)(P0.05)。结论:ERCP与PTCD治疗恶性梗阻性黄疸均可改善患者肝脏功能、疗效满意,但ERCP对低位梗阻患者治疗效果优于PTCD,且术后舒适度优于PTCD,但术后并发症较多,临床应根据患者情况选择具体术式。     

经皮肝穿刺胆道引流术与逆行胰腺胆管造影术对结石性梗阻性黄疸患者的疗效比较研究

目的:比较经皮肝穿刺胆道引流术(PTCD)与逆行胰腺胆管造影术(ERCP)对结石性梗阻性黄疸患者的治疗效果。方法:选取海军军医大学第三附属医院东方肝胆外科医院于2016年3月～2018年4月间收治的结石性梗阻性黄疸患者80例。按照介入治疗术式的异同将患者分为ERCP组(n=40,给予ERCP治疗)和PTCD组(n=40,给予PTCD治疗),记录两组手术时间、术中出血量、住院费用、住院时间、治疗成功率、黄疸缓解率、并发症发生情况,比较两组术前、术后1 d、术后7 d肝功能指标情况。结果:两组患者手术时间、术中出血量、治疗成功率、黄疸缓解率比较差异无统计学意义(P0.05),ERCP患者住院费用少于PTCD组患者,住院时间亦短于PTCD组患者(P0.05)。两组患者术后1 d、术后7 d丙氨酸转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)水平均较术前降低,且两组患者术后7 d上述指标水平低于术后1 d(P0.05),ERCP组术后1 d、术后7 d ALT、TBIL、DBIL水平与PTCD组比较差异无统计学意义(P0.05)。两组患者术后并发症总发生率比较差异无统计学意义(P0.05)。结论:PTCD、ERCP治疗结石性梗阻性黄疸,均能有效改善患者临床症状和肝功能,且手术安全性相当,但ERCP可明显减少住院时间和住院费用。     

Effects of Ellagic Acid on Copper,Zinc, and Biochemical Values in Serum and Liver of Experimental Cholestatic Rats

Ellagic acid (EA) is a natural polyphenolic compound. Although, modulator effects of EA on copper (Cu) and zinc (Zn) levels in some liver diseases have been reported in experimental animals, its effects in obstructive jaundice (OJ) has not been clarified. We aimed to evaluate potential effects of EA on Cu and Zn levels in liver and serum of cholestatic rats. Forty Wistar albino rats were equally divided into four groups. First group was used as controls. Second group received EA (60 mg⁻¹ kg⁻¹ day⁻¹) for 8 days. Third was OJ group, and fourth group was OJ plus EA group. After 8 days, blood and liver samples were obtained. Higher serum and liver Cu and lower serum and liver Zn levels were found in OJ group (p < 0.05) compared with other groups. However, these differences reached to significant levels for Cu in serum and for Zn in lever. Higher serum copper levels were decreased, and lower liver Zn levels were increased by EA treatment in cholestatic rats (p < 0.05). Also, higher Cu/Zn ratio in OJ group was decreased by EA treatment both in liver (p < 0.05) and in serum (p < 0.05). Significantly higher serum bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase values were found in OJ and OJ + EA groups compared with the control and EA groups (p < 0.05). In conclusion, result of the current study indicated that ellagic acid has modulator effects on Cu and Zn levels in liver and serum of cholestatic rats.     

更昔洛韦联合大剂量丙种球蛋白治疗婴儿巨细胞病毒性肝炎的疗效观察

目的:研究更昔洛韦联合大剂量丙种球蛋白治疗婴儿巨细胞病毒性(CMV)肝炎的临床疗效,为婴儿CMV肝炎的抗菌治疗提供理论依据。方法:选取我院自2009年7月至2016年1月收治的103例CMV肝炎婴儿,根据随机数字表法分为治疗组58例,对照组45例。两组患儿均常规给予退黄、保肝药物治疗,对照组在此基础上给予更昔洛韦治疗,治疗组给予大剂量丙种球蛋白联合更昔洛韦治疗。对比观察两组患儿治疗后黄疸消退情况、肝功能变化、血CMV-IgM和尿CMV-DNA转阴情况、肝和脾B超变化、治疗效果及不良反应情况。结果:治疗组患儿黄疸消退时间、血CMV-IgM和尿CMV-DNA转阴时间均短于对照组(P0.05);治疗组肝功能指标包括总胆红素(TBIL)、直接胆红素(DBIL)、丙氨酸氨基转移酶(ALT)、γ-谷氨酰转肽酶(GGT)水平均较对照组和治疗前降低(P0.05);治疗后两组肝、脾明显减小,且治疗组减小更显著,差异有统计学意义(P0.05);治疗组中血CMV-IgM转阴率、尿CMV-DNA转阴率、治疗总有效率均高于对照组(P0.05);治疗组不良反应发生率低于对照组(P0.05)。结论:更昔洛韦联合大剂量丙种球蛋白治疗婴儿CMV肝炎临床效果良好,可以有效缓解黄疸症状,恢复肝脏功能,肝、脾回缩明显,不良反应少,值得推广。     

双歧杆菌对梗阻性黄疸大鼠肠道细菌移位影响的研究

目的观察梗阻性黄疸大鼠肠道细菌移位状况及经胃肠道给予双歧杆菌对肠道细菌移位的影响。方法Wistar大鼠30只随机分为3组：假手术组（SO组）、梗阻性黄疸组（OJ组）及双歧杆菌组。模型制备后第10天检测各组肝功能指标及血浆内毒素水平,取肝、脾、肠系膜淋巴结等肠道外器官组织行细菌培养,光镜观察末端回肠黏膜变化。结果 OJ组较SO组肝功能指标明显改变（P〈0．05）,双歧杆菌组肝功能指标较OJ组改善。SO组血浆内毒素水平为（0．26±0．22）EU／ml,OJ组内毒素水平为（1．99±0．31）EU／ml,较SO组明显升高（P〈0．01）,双歧杆菌组血浆内毒素水平为（0．74±0．20）EU／ml,较OJ组明显降低（P〈0．01）。OJ组肝、脾、肠系膜淋巴结中细菌移位率高于另两组,其中肠系膜淋巴结细菌移位率为90％,明显高于SO组及双歧杆菌组（P〈0．05）。光镜显示OJ组肠黏膜萎缩,绒毛水肿,部分上皮细胞脱落;双歧杆菌组肠黏膜上皮改变较OJ组明显减轻。结论梗阻性黄疸时出现明显的细菌移位与内毒素血症。应用微生态制剂可保护梗阻性黄疸时小肠黏膜屏障功能,减少肠源性细菌移位及内毒素血症的发生。     

肝动脉化疗栓塞联合射频消融对中晚期肝癌患者血清肿瘤活性因子、肝功能和预后的影响

目的:探讨肝动脉化疗栓塞(TACE)联合射频消融(RFA)对中晚期肝癌患者血清肿瘤活性因子、肝功能和预后的影响。方法:选取2012年2月～2016年6月期间我院收治的中晚期肝癌患者103例,根据随机数字表法将患者分为对照组(n=51)和研究组(n=52),对照组患者给予RFA治疗,研究组给予TACE联合RFA治疗,比较两组临床总有效率,比较两组治疗前后肝功能、血清肿瘤活性因子水平,统计两组患者并发症情况和预后。结果:治疗后研究组临床总有效率为53.85%(28/52),高于对照组患者的33.33%(17/51)(P0.05)。两组患者治疗后总胆红素(TBIL)、丙氨酸转氨酶(ALT)、氨基酸转氨酶(AST)较治疗前降低(P0.05),但两组治疗后TBIL、ALT、AST比较差异无统计学意义(P0.05)。两组患者治疗后甲胎蛋白(AFP)、糖类抗原199(CA199),基质金属蛋白酶(MMP)均较治疗前降低,且研究组低于对照组(P0.05)。两组患者并发症发生率比较无差异(P0.05)。研究组患者治疗后1年、2年复发率低于对照组,生存率高于对照组(P0.05)。结论:TACE联合RFA治疗中晚期肝癌,疗效确切,可有效降低血清肿瘤活性因子水平,未加重肝功能损伤,且可改善患者的预后。     

Effects of oral <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis> on hepatocyte tight junction structure and function in rats with obstructive jaundice

Surgery and infection are prominent risk factors for the development of obstructive cholestasis which in turn is associated with failure of the liver barrier. We studied the effects of oral Lactobacillus plantarum (LP) supplementation on endotoxemia, oxidative stress, apoptosis, and tight junctions of hepatocytes in an experimental model of obstructive jaundice. Fifty male Wistar rats were randomly divided into five groups of 10 each: group I, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BLD followed by oral LP treatment; group IV, BDL followed by internal biliary drainage (IBD); group V, BDL followed by IBD and oral LP treatment. Hepatocyte apoptosis, plasma reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, and portal blood endotoxin levels were measured and changes in tight junction-associated proteins occludin, claudin-1, claudin-4, and ZO-1 were observed. Compared to the sham-operated group I, significant increases in endotoxemia, apoptosis, and GSSG were observed in group II and significant decreases were observed in group V. Tight junctions were destroyed in group II animals but were not in animals treated with oral LP (groups III and V). An increase in occludin, claudin-1, claudin-4, and ZO-1 mRNA and protein levels were detected in livers in LP-treated animals (group V) compared with group II levels. Oral LP treatment of rats with obstructive jaundice assisted in the return of active hepatic barrier function. These results may lead to treatments to prevent the deleterious effects of obstructive jaundice.     

Protective effect of L-carnitine on experimental lead toxicity in rats: a clinical,histopathological and immunohistochemical study

Abstract

Female Wistar-albino rats were given lead acetate (PbAc) for 60 days to investigate the protective effects of L-carnitine (CA) clinically and histopathologically on PbAc-induced tissue damage. Blood samples were obtained from the jugular vein for hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), white blood cells (WBC), platelets (PLT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine. PbAc treatment caused a significant decrease in HB, HCT and RBC, a significant increase in WBC, AST, ALT and creatinine compared to controls. Although administration of CA did not reverse HB and HCT values, it reversed both the decrease in RBC and the increase in WBC, AST, ALT and creatinine. After the experimental period, all rats were weighed, then decapitated for pathological examination. Control rat liver, kidney and brain showed normal histological architecture. Lead-induced nephropathic kidneys; degenerative changes, inflammation and portal edema of the liver; and brain neuropil vacuolation, neuronal vacuolation, satellitosis and neuronophagia were observed in experimental groups. All changes were reduced in the PbAc group treated with CA (PbAc + CA). PbAc caused copper/zinc superoxide dismutase (Cu/Zn-SOD) expression in both the hepatocytes and tubular epithelium of the kidney. PbAc + CA exposure caused moderate Cu/Zn-SOD immunoreactivity. While in the brain sections of the PbAc group the degenerative neurons were stained intensely with anti-ubiquitin antibody, PbAc + CA rats showed moderate staining in neurons with anti-ubiquitin antibody. These results show that CA as a food additive reduced the severity of tissue damage caused by PbAc.     

异甘草酸镁对胆道梗阻致肝损伤肝功能保护作用的动物实验研究

目的:探讨异甘草酸镁注射液对大鼠梗阻性黄疸肝损伤的保护作用。方法:选用健康雄性SD大鼠32只,随机分成4组,每组各8只,分别为胆总管结扎+异甘草酸镁注射液常规剂量组(BMc组);胆总管结扎+异甘草酸镁注射液高剂量组(BMh组);胆总管结扎+0.9%生理盐水注射液组(BN组)和假手术组(Sham组)。BN和Sham组以生理盐水30 mg/kg/日腹腔注射,BMc组以异甘草酸镁30 mg/kg/日腹腔注射,BMh组以异甘草酸镁60 mg/kg/日腹腔注射。术后不同时间对各组大鼠眼眶取血并获得血清。在全自动生化分析仪器检测肝功能指标:丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、直接胆红素(Direct bilirubin,DBil)。结果:BN、BMc和BMh组大鼠在胆管结扎后血清中ALT和AST指标明显升高。随着梗阻时间的增加,BM和BMh组大鼠血清中ALT和AST的水平均明显低于BN组(P0.01),但两组之间并无明显区别。手术后BN、BMc和BMh组大鼠在胆管结扎后血清中D-Bil水平明显高于Sham组(P0.01),但随着梗阻时间的延长,各组间D-Bil的水平变化不明显。结论:异甘草酸镁注射液可以有效降低梗阻性黄疸大鼠血清转氨酶水平,对肝功能有明显的保护作用。     

Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL+BBS (10 μg/kg, s.c. ×3), BDL+NT (300 μg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.     

S-腺苷蛋氨酸对梗阻性黄疸患者术后肝功能及营养状况影响的临床研究

目的：探讨S-腺苷蛋氨酸对梗阻性黄疸患者术后肝功能及营养状况的影响。方法：选择2010年8月至2012年7月我院肝胆病区收治的90例梗阻性黄疸患者为研究对象,随机分为S-腺苷蛋氨酸治疗组（48例）和对照组（42例）,比较和分析静脉滴注S-腺苷蛋氨酸对梗阻性黄疸患者术后第5d、10d肝功能及营养指标的影响。结果：术后5d、10d,两组患者血总胆红素、直接胆红素、谷丙转氨酶、1．谷氨酰转肽酶、碱性磷酸酶水平较术前1d显著降低,且组内比较差异有统计学意义（P〈0．05）,治疗组以上指标的下降程度较对照组更明显,差异有统计学意义（P〈0．05）。术后第10d,两组患者的血白蛋白、前白蛋白、转铁蛋白水平较术后第5d显著改善（P〈0．05）;术后第5、10d,两组组间血白蛋白、前白蛋白、转铁蛋白水平比较差异有统计学意义（P〈0．05）。结论：梗阻性黄疸患者术后应用腺苷蛋氨酸能促进黄疸消退,加快胆红素的排泄和肝功能的恢复,有利于患者营养状况的改善。     

Assessment of the protective and therapeutic effect of melatonin against thioacetamide‐induced acute liver damage

Acute or chronic damage to the liver may occur through alcohol, drugs, viruses, genetic disorders, and toxicity. In this study, we planned to investigate the protective and therapeutic effects of melatonin (Mel) by causing damage to the liver with thioacetamide (TAA). Thirty‐five rats were used. Group I: control group (seven pieces), group II: Mel group (seven pieces) the single dose on the first day of the experiment was 10 mg/kg, group III: TAA (seven pieces) 300 mg/kg with 24‐hour intervals, two doses, group IV: Mel + TAA group (seven pieces) 10 mg/kg single dose Mel was applied 24 hours before TAA application, group V: TAA + Mel group (seven pieces) single dose (24th hour) of 10 mg/kg Mel was administered after TAA (300 mg/kg) two doses. The liver histology was evaluated. Apoptosis, autophagy, and necrosis markers in tissue were determined by immunohistochemistry. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in blood serum samples and transforming growth factor‐β (TGF‐β) and tumor necrosis factor‐α (TNF‐α) levels were determined in liver tissue. TAA affected histologically the classical lobule structure both in cell cords and sinusoids. Caspase‐3, RIP3, and LC3 levels were increased in group III compared with the control group. TAA did not cause a statistically significant change in TNF‐α level but decreased the TGF‐β level significantly. AST and ALT levels were statistically significant in group II and V compared with group I, the ALP level was significant in group IV compared with group II. The results of this study showed that TAA caused significant damage to tissues and increased cell death, Mel was found to have more therapeutic than the protective effect on tissues.     

Effects of maternal treatment of dehydroepiandrosterone (DHEA) on serum lipid profile and hepatic lipid metabolism-related gene expression in embryonic chickens

Over the last decade, much evidence emerged to suggest that alterations in maternal diets during pregnancy may irreversibly affect aspects of physiological and biochemical functions in the fetus. To explore the effects of maternal dietary treatments with dehydroepiandrosterone (DHEA) on lipid metabolism in the embryo, we investigated serum lipid profile and hepatic lipid metabolism-related gene expression in the maternal and embryonic chicken. Sixteen-week-old pullets were allocated into 3 groups (n = 30), and after laying, they were provided with a commercial diet supplemented with DHEA at 0, 20 or 100 mg/kg diet. Eggs were collected after DHEA treatment and incubated at 37.5 °C and a relative humidity of 60%. Blood and liver samples were collected from hens and embryonic chickens. DHEA treatment resulted in decreased body weight and increased relative liver weight in both maternal and embryonic chickens, while the concentrations of blood triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and non-esterified fatty acid (NEFA) were significantly lower in the 20 mg DHEA/kg group as compared to the control group during embryonic development. The expression of acetyl CoA carboxylase (ACC) and carnitine palmitoyl transferase I (CPTI) gene was also reduced following treatment with 20 mg DHEA/kg at hatching. However, blood TC, and hepatic fatty acid synthase (FAS) and hydroxy methylglutaryl-CoA reductase (HMGR) gene expression were significantly up-regulated in the 100 mg DHEA/kg group during embryonic development and hatching. Overall, the results of this study indicate that maternal dietary treatment with DHEA regulates serum lipid metabolism and hepatic gene expression.     

Dehydroepiandrosterone improves hepatic antioxidant reserve and stimulates Akt signaling in young and old rats

This study examined, in the liver of young and old (3- and 24-month-old, respectively) healthy Wistar rats, the in vivo effect of dehydroepiandrosterone (DHEA) (10mg/kg body weight) administered subcutaneously for 5 weeks. Reduced (GSH) and oxidized (GSSG) glutathione levels, glucose-6-phosphate dehydrogenase (G6PDH), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities, hydrogen peroxide concentration, GST and p-Akt/Akt immunocontent ratio were assessed in hepatic tissue. DHEA treatment significantly increased total glutathione content (17%) and GSH (22%) in 3- and 24-month-old treated groups when compared to control groups. The aging factor increased G6PDH (51%) and GPx (22%) activities as well as the hydrogen peroxide concentration (33%), independently of treatment. DHEA treatment increased p-Akt (54%) and p-Akt/Akt ratio (36%) immunocontents in both treated groups. Increased serum levels of alanine aminotransferase (ALT) in aged rats were reduced by DHEA treatment (34%).     

Protective effects of melatonin against carbon tetrachloride-induced hepatotoxicity in rats: a light microscopic and biochemical study

The aim of this study was to examine the protective effects of melatonin against CCl4-induced hepatotoxicity in the rat. Twenty-four male Wistar rats were divided into three groups. Group I was used as a control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and melatonin for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and conjugated bilirubin levels were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All serum biochemical parameters were significantly higher in animals treated with CCl4 than in the controls. When rats injected with CCl4 were treated with melatonin, significantly reduced elevations in serum biochemical parameters were found. In liver sections of the CCl4-injected group, necrosis, fibrosis, mononuclear cell infiltration, haemorrhage, fatty degeneration and formation of regenerative nodules were observed. Additionally, apoptotic figures, microvesicular steatosis and hydropic degeneration in hepatocytes were seen in this group. In contrast, the histopathological changes observed after administration of CCl4 were lost from rats treated with CCl4 and melatonin. Except for mild hydropic degeneration of the hepatocytes, a normal lobular appearance was seen in the livers of this group. The results of our study indicate that melatonin treatment prevents CCl4-induced liver damage in rats.     

Effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption

This study examined the effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and β‐carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and α‐tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with β‐carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing β‐carotene. The results indicate that β‐carotene supplementation can prevent ethanol‐induced liver damage and increase GSH concentrations in erythrocytes and the liver. Copyright © 2009 John Wiley & Sons, Ltd.     

Magnesium Lithospermate B Reduces Inflammatory Response in a Mouse Model of Hepatic Ischemia–Reperfusion Injury

It has been well proved that acute inflammatory response and hepatocellular apoptosis contributed to the pathogenesis of liver ischemia reperfusion (IR) injury. A vast amount of research has demonstrated that magnesium lithospermate B (MLB) has potent anti-apoptosis and potential anti-inflammatory pharmacological properties. However, it has not previously been examined whether MLB can attenuate hepatic IR injury. Firstly, the optimal dose of MLB to protect against hepatic IR injury was determined using hepatic IR model in mice. Then, the effect of MLB on IR-induced inflammatory response was detected in detail. We found that MLB exhibited protective effect from the beginning of 50 mg/kg and culminated at the doses of 100 and 200 mg/kg. The alanine aminotransferase and aspartate aminotransferase levels in MLB group were markedly decreased. Severe hepatocellular swelling/necrosis, sinusoidal/vascular congestion and inflammatory cell infiltration were seen and a large number of apoptotic cells were found in the liver samples from Saline group, while minimal damage and very few apoptotic cells were noted in the samples from MLB group. Kuppfer cells infiltration, myeloperoxidase activity and mRNA level of CD11b in MLB group was significantly decreased. Serum TNF-a and IL-6, and mRNA expression of CXCL-10 and ICAM-1 was markedly decreased in the samples from MLB group. Inflammatory signaling pathway activation was largely prevented in MLB group. MLB can significantly attenuate IR-induced hepatocellular damage and hepatocellular apoptosis by preventing inflammatory signaling pathways activation, inflammatory mediators expression and macrophage and neutrophil infiltration.     

Kaempferol attenuates liver fibrosis by inhibiting activin receptor–like kinase 5

Liver fibrosis is a common public health problem. Patients with liver fibrosis are more likely to develop cirrhosis, or hepatocellular carcinoma (HCC) as a more serious consequence. Numerous therapeutic approaches have emerged, but the final clinical outcome remains unsatisfactory. Here, we discovered a flavonoid natural product kaempferol that could dramatically ameliorate liver fibrosis formation. Our data showed that intraperitoneal injection of kaempferol could significantly decrease the necroinflammatory scores and collagen deposition in the liver tissue. In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), laminin (LN) and hyaluronic acid (HA) levels were significantly down‐regulated in kaempferol treatment group compared with those in the control group. Our study also demonstrated that kaempferol markedly inhibited the synthesis of collagen and activation of hepatic stellate cells (HSCs) both in vivo and in vitro. Furthermore, the results of Western blotting revealed that kaempferol could down‐regulate Smad2/3 phosphorylation dose‐dependently. These bioactivities of kaempferol may result from its targeted binding to the ATP‐binding pocket of activin receptor–like kinase 5 (ALK5), as suggested by the molecular docking study and LanthaScreen Eu kinase binding assay. Above all, our data indicate that kaempferol may prove to be a novel agent for the treatment of liver fibrosis or other fibroproliferative diseases.     

Investigate of AQP gene expression in the liver of mice after ischemia–reperfusion

Ischemia–reperfusion (IR) injury usually occurs during liver transplantation. Aquaporins (AQPs) are transmembrane channels that facilitate water permeability through cell membranes and are essential for the regulation of water homeostasis. Changes in the AQPs expression have been correlated with several inflammatory diseases. Less is known about AQPs expression in hepatic ischemia reperfusion injury. To clarify the roles of AQPs in IR injury, in this current study we examined the gene expression patterns of AQP1, 8 and 9 in the liver after IR injury. Male balb/c mice were exposed to partial (70%) hepatic ischemia for 65 min and then randomized into five groups of reperfusion [0 h (A), 8 h (B), 1 day (C), 3 days (D), and 7 days (E)]. A surgical group was also selected as the sham group. Serum and liver tissue samples were collected for evaluation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver histopathology. Real time PCR was performed to evaluate the AQPs expression. I/R injury resulted in a significant increase in ALT and AST (p?<?0.05) compared to sham mice in each group. The gene expression of AQPs was significantly increased in the IR group compared with the sham group (p?<?0.05). AQP8 and AQP1 after 8 h (group B) showed the highest gene expression in comparison with other groups, but the highest level of AQP9 gene expression was observed after 1 day (group C). Pathologic changes in the liver after reperfusion were confirmed the IR. In the IR group cytoplasmic vacuolization, inflammatory cell infiltration and focal necrosis were detected. In conclusion, our findings indicated that the damage caused by ischemia–reperfusion in the liver can change the expression of AQP genes, which can interfere with hepatocellular homeostasis and their function. Upregulation of AQP1, 8 and 9 could contribute to the development of hepatocellular swelling after hepatic IR injury.     

腹腔镜解剖性肝切除治疗肝细胞癌的临床观察

目的:探讨腹腔镜解剖性肝切除治疗肝细胞癌的临床效果及安全性。方法:选择2011年2月~2013年8月在我院进行诊治的肝细胞癌患者90例,将其随机分为治疗组与对照组,每组各45例。治疗组采用腹腔镜解剖性肝切除治疗,对照组采用开腹解剖性肝切除,两组术后都常规化疗3个月,观察和比较两组术中出血量、术后肛门排气时间和术后住院时间,并发症的发生情况及术前后血清谷氨酸转移酶(ALT)与天冬氨酸转移酶(AST)的水平。结果:与对照组相比,治疗组的术中出血量、术后肛门排气时间和术后住院时间均明显降低或缩短(P0.05),术后3个月的膈下积液、切口感染、肺部感染、胆漏的发生率明显降低(P0.05)。两组术前血清ALT与AST值对比差异无统计学意义(P0.05);术后1周,两组的ALT与AST值都明显升上(P0.05);术后3个月,治疗组的ALT与AST值明显低于对照组(P0.05)。所有患者随访到2015年8月,治疗组的中位生存期为(18.33±3.11)个月,而对照组为(12.46±2.19)个月,较治疗组明显缩短(P0.05)。结论:腹腔镜解剖性肝切除治疗肝细胞癌具有更好的微创性,能减少近期并发症的发生,促进肝功能的恢复,且能够延长患者的生存时间。