Liver Ischemia and Ischemia–Reperfusion Induces and Trafficks the Multi-specific Metal Transporter Atp7b to Bile Duct Canaliculi: Possible Preferential Transport of Iron into Bile

Both Atp7b (Wilson disease gene) and Atp7a (Menkes disease gene) have been reported to be trafficked by copper. Atp7b is trafficked to the bile duct canaliculi and Atp7a to the plasma membrane. Whether or not liver ischemia or ischemia–reperfusion modulates Atp7b expression and trafficking has not been reported. In this study, we report for the first time that the multi-specific metal transporter Atp7b is significantly induced and trafficked by both liver ischemia alone and liver ischemia–reperfusion, as judged by immunohistochemistry and Western blot analyses. Although hepatocytes also stained for Atp7b, localized intense staining of Atp7b was found on bile duct canaliculi. Inductive coupled plasma-mass spectrometry analysis of bile copper, iron, zinc, and manganese found a corresponding significant increase in biliary iron. In our attempt to determine if the increased biliary iron transport observed may be a result of altered bile flow, lysosomal trafficking, or glutathione biliary transport, we measured bile flow, bile acid phosphatase activity, and glutathione content. No significant difference was found in bile flow, bile acid phosphatase activity, and glutathione, between control livers and livers subjected to ischemia–reperfusion. Thus, we conclude that liver ischemia and ischemia–reperfusion induction and trafficking Atp7b to the bile duct canaliculi may contribute to preferential iron transport into bile.     

肝移植术后营养治疗

近30多年来,肝移植技术已逐步成熟,并迅速发展成为治疗终末期肝病的首选方法。随着肝移植例数的增加,手术经验的积累,手术技巧的提高,与手术相关的并发症逐渐减少。而许多围手术期因素成为影响肝移植成败的关键。适宜的肝移植围手术期营养治疗,可以提高手术成功率,降低术后并发症,促进受体和移植肝功能的恢复,从而改善预后,提高受体与移植肝的近远期存活率。     

Changes in the proteome of Huh7 cells induced by transient expression of hepatitis D virus RNA and antigens

Hepatitis delta virus (HDV) infection of human hepatocytes infected with the hepatitis B virus (HBV) is associated with increased liver damage and risk of fulminant disease. Although considerable progress has been made towards the elucidation of the mechanisms of HDV replication and pathogenesis, little is still known about the host factors involved in the different steps of the replication cycle. Here, we made use of a proteomic approach to analyse the global alterations in protein expression that arise in human hepatocytes separately transfected with each of the HDV components. Huh7 cells were transiently transfected with plasmids that code for the small delta antigen (S-HDAg), large delta antigen (L-HDAg), genomic RNA (gRNA), and antigenomic RNA (agRNA), respectively. Total protein extracts were separated by 2-DE and differentially expressed spots were identified by MALDI-TOF followed by database searching. We identified 32 proteins known to be involved in different pathways namely nucleic acid metabolism, protein metabolism, transport, signal transduction, apoptosis, and cell growth. Moreover, the down regulation of hnRNP D, HSP105, and triosephosphate isomerase was further confirmed by Real time PCR.     

Plasma transport and tissue distribution of β-carotene, vitamin A and retinol-binding protein in domestic cats

The objective of this study was to determine retinol, retinyl esters and retinol-binding protein (RBP) as well as carotenoids in plasma, urine, liver and kidneys of randomly selected domestic cats. Retinol (240±64 ng/ml, mean±S.D.) represented one-third of total retinyl esters (736±460 ng/ml) in plasma. Retinyl esters were stearate, palmitate and oleate representing 61±6, 36±13 and 5±3% of total retinyl esters, respectively. In half of the cats, retinyl esters (22±21 ng/ml) were found in the urine. Vitamin A in the livers (4317±1956 μg/g) was significantly higher than in the kidney cortex and medulla (14.16±8.92 and 7.59±4.52 μg/g, respectively, both P<0.001). RBP was detected in the plasma but not in the urine. Immunoreactive RBP was observed in hepatocytes and in the cells of the proximal tubules. β-Carotene was present in plasma but never in tissues. The results show that similar to canines differences in vitamin A metabolism in cats are related to the occurrence of retinyl esters in plasma. They differ, however, with regard to the tissue distribution of β-carotene and the excretion of vitamin A in the urine.     

Quantitative Proteomics and Targeted Fatty Acids Analysis Reveal the Damage of Triptolide in Liver and Kidney

Triptolide (TP), the major active component in Tripterygium wilfordii Hook. f., is widely used for the treatment of rheumatoid arthritis and autoimmune diseases. However, organ toxicity, especially hepatotoxicity and nephrotoxicity, limits its clinical application. To fully understand the mechanism underlying TP toxicity, iTRAQ‐based 2D‐LC‐MS/MS proteomics is used to detect differentially expressed proteins in the livers and kidneys of mice administered the LD50 dose of TP. Functional annotation revealed that multiple pathways are involved in TP toxicity, including acute‐phase response signaling, the antigen presentation pathway, FXR/RXR activation, LPS/IL‐1‐mediated inhibition of RXR function, and EIF2 signaling. Members of the cytochrome P450 protein family that are involved in fatty acid (FA) metabolism, such as CYP2E1, show significant differences in expression among groups. Additionally, the proteomics data suggested that FAs are involved in TP‐induced toxicity. FA analysis is conducted using HPLC‐MRM to characterize the differences among various groups exposed to TP for different times. It has been found that 20 FAs in the liver show significant differences in abundance among groups, whereas in the kidneys, six FAs show significant differences in abundance. By integrating the proteomic and targeted FA analyses, it has been found that differently expressed proteins and FAs both participate in pathways including cellular lipolytic activity, peroxisomal fatty acid beta‐oxidation, and so on. Our data contribute to understanding the mechanisms underlying TP‐induced organ toxicity. The results may help to improve the clinical efficacy and safety of TP in the future.     

草鱼不同组织胆汁酸组成分析

正胆汁酸是由胆固醇通过一系列酶促反应在肝细胞中合成的,根据侧链羟基数目的多少胆汁酸分为初级胆汁酸和次级胆汁酸。初级胆汁酸随食物到达肠道,在肠道微生物的作用下脱羟基形成次级胆汁酸~([1])。初级胆汁酸和次级胆汁酸都可与牛磺酸或者甘氨酸结合形成结合型胆汁酸。肝脏中合成的以及经由肠肝循环回到肝脏的胆汁酸都被储存在胆囊中。胆汁酸的主要生理功能是帮助脂溶性营养物质的消化吸收,高脂肪的摄入刺激胆汁酸     

Protective effect of some plant oils on diazinon induced hepatorenal toxicity in male rats

Environmental pollution and exposure to environmental pollutants are still some of the major global health issues. Pesticides have been linked to a wide range of health hazards. The toxicity of pesticides depends on several factors such as its chemical properties, doses, exposure period, exposure methods, gender, genetics, age, nutritional status and physiological case of exposed individuals. Medicinal plants, natural products and nutrition continue to play a central role in the healthcare system of large proportions of the world’s population. Alternative medicine plays an important role in health services around the world. The aim of this study was to investigate the effect of olive, sesame and black seed oils on hepatorenal toxicity induced by diazinon (DZN) in male rats. The experimental animals were divided into nine groups. The first group served as control. The second group was exposed to DZN. The third group was treated with olive oil and DZN. Rats of the fourth group were subjected to sesame oil and DZN. Rats of the fifth group were exposed to black seed oil and DZN. The sixth, seventh and eighth groups were supplemented with olive, sesame and black seed oils respectively. Rats of the ninth group were treated with corn oil. Levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, total bilirubin, creatinine, blood urea nitrogen and malondialdehyde were significantly increased in rats exposed to DZN. Moreover, levels of serum glutathione and superoxide dismutase were significantly decreased. Several histopathological changes were observed in the structures of liver and kidney due to DZN exposure. This study showed that these oils attenuated the physiological disturbances and histopathological alterations induced by DZN intoxication. Moreover, the antioxidant properties of these oils support the bioactive roles of its protective effects on DZN toxicity. This study therefore suggests that these oils could be used as preventive factors against the toxicity of DZN due to its antioxidant properties.     

Liver and kidney toxicity induced by Afzal smokeless tobacco product in Oman

Afzal, the common smokeless tobacco product (STP) in Oman, is believed to contain toxins that may impair the function of some organs such as liver and kidney. An aqueous extract from Afzal was added to drinking water to be administrated orally to Wistar albino rats (n = 72) young and adult from both genders weighing between 60–80 g and 150–240 g respectively for 8 weeks. Animals were divided into three groups: control (distilled water instead of Afzal extract), low-dose (3 mg nicotine/kg body weight/day) and high-dose (6 mg nicotine/kg body weight/day). The animals were euthanized and their blood, liver and kidney were collected for biochemical and histopathological investigations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed for the liver function, while blood urea nitrogen (BUN) and creatinine (CRT) were assayed for the kidney function. The results showed a significant increase in the ALT, AST, BUN and CRT levels (P < 0.05) in both Afzal-treated groups (low and high doses) compared with the control. Histopathological findings revealed the initial but seem to be serious degenerative alterations of periportal fibrosis in liver and edematous and calcified changes in renal glomerulus among Afzal-treated groups. Additionally, the weight gain of the Afzal-treated groups was lower than the control group. Our findings show that the exposure of Wistar rats to the Afzal extract has the potentials of causing decreased weight gain and dose-dependent functional and structural damage to the biochemical and histological profiles of liver and kidney as well as serious biochemical effects.     

MRI和螺旋CT增强在肝脏占位性病变诊断中的价值比较

目的:对比分析MRI和螺旋CT增强在肝脏占位性病变诊断中的价值。方法:以2012年7月-2016年5月我院收治的临床考虑为肝脏占位性病变70例患者为研究对象,将70例患者根据入组先后顺序分为两组,35例行增强CT扫描,35例行动态增强MRI扫描,比较两组患者的病理诊断结果、病灶个数及直径、增强CT及MRI的诊断结果和检查过程中的不良反应及耐受性。结果:CT增强组和MRI增强组的肝脏占位性病变的病理诊断、病变类型、分布及病灶个数(71 vs 70)、病灶直径(2.25±2.01 cm vs2.19±1.98 cm)比较差异均无统计学意义(P0.05);以病理诊断结果为金标准,MRI增强组的总诊断符合率为85.71%,CT增强组的总诊断符合率为77.14%,MRI增强组的总诊断符合率高于CT增强组,但差异无统计学意义(P0.05);CT增强组共发生2例不良反应,均为轻度恶心,MRI增强组未出现造影剂不良反应,CT增强组的不良反应发生率(5.71%vs 0.00%)及视觉模拟评分法(VAS)评分(1.25 0.96分vs 0.71 0.56分)均显著高于MRI增强组(P0.05)。结论:CT增强和MRI增强扫描对于肝脏占位性病变的诊断均具有较高的临床价值,其中MRI增强扫描的安全性和耐受性更高,临床医师可根据患者的经济状态、身体状态等因素的综合评估,选择合适的检查手段,必要时可两者联合检查,以提高诊断的准确性。     

稳心颗粒与瑞舒伐他汀治疗老年冠心病的临床疗效及安全性

目的:探究稳心颗粒联合瑞舒伐他汀治疗老年冠心病患者临床疗效及安全性。方法:选取42例本院收治的老年冠心病患者,按照随机数字表法分为实验组和对照组。对照组21例,予美托洛尔片25 mg,起始量12.5 mg/日口服,日2次,如无首剂反应将剂量加至25 mg/日,日2次,瑞舒伐他汀片10 mg口服,日1次;实验组21例予稳心颗粒9g温开水冲服,日3次,瑞舒伐他汀10 mg口服,日1次。治疗28天后,观察和比较两组患者治疗前后CK-MB、肝功能及临床疗效。结果:治疗后,实验组有效率(95.2%)显著高于对照组(81.0%),差异有统计学意义(P0.05)。与治疗前相比,两组患者治疗后谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBil)、胱抑素C水平、左室射血分数(LVEF)均升高(P0.05),总胆固醇(TC)、低密度脂蛋白(LDL-C)水平及磷酸肌酸激酶同工酶(CK-MB)水平均降低(P0.05)。与对照组相比,实验组LVEF及胱抑素C水平较高(P0.05)。结论:稳心颗粒联合瑞舒伐他汀治疗老年冠心病患者可有效降低血脂,缓解患者胸闷、心悸等症状,对肝脏及肾脏功能损伤小,且安全性高。