Notch-Hif-1-alpha信号通路参与调控大鼠肝再生过程的研究

目的：探讨使用酌分泌酶抑制剂Fli-06 特异性阻断Notch 信号通路后,大鼠肝部分切除术后肝再生的情况并初步阐明 Notch-Hif-1-alpha信号通路调控肝再生的可能机制。方法：取SD 大鼠分为对照（生理盐水注射组,n=24）和抑制剂组（酌分泌酶抑制剂 注射组,n=24）。给予药物处理后,两组分别施行大鼠肝部分切除术,术后0 d,1 d,3 d,5 d,每个时间点分别留取对照组（n=6）及抑 制剂组（n=6）再生的肝组织,并检测相应肝重体重比,免疫组化法检测再生肝PCNA（增殖细胞核抗原,Proliferation Cell Nuclear Antigen）表达,RT-PCR 检测再生肝组织中的Notch1、Hes1、VEGF mRNA的变化,Western-Blot 法检测NICD（Notch 胞内段,Notch Intracellular Domain）、Hif-1-alpha（低氧诱导因子-1-alpha,Hypoxia Inducible Factor-1琢)蛋白在肝再生过程的变化情况。结果：1、肝部分切除 术后3 d和5 d,抑制剂组肝重体重比明显低于对照组差异有统计学意义（P<0.05）;2、免疫组织化学染色结果提示：抑制剂组再生 肝PCNA阳性细胞率在术后1 d,3 d,5 d 均明显低于对照组（P<0.05）;3、Western blot 结果表明：NICD 和Hif-1-alpha蛋白水平明显低 于对照组（P<0.05）;同时RT-PCR 结果提示：抑制剂组Hes1 的mRNA表达量术后1 d,3 d明显低于对照组,差异具有统计学意义 （P<0.05）。同时,抑制剂组VEGF mRNA 水平在术后3 d,5 d明显低于对照组,差异具有统计学意义（P<0.05）。结论：在大鼠肝部分 切除术后肝再生过程中,使用酌分泌酶抑制剂Fli-06 抑制Notch 信号通路后,大鼠的肝再生能力明显降低,Notch-Hif-1alpha信号通 路可能参与调控了大鼠肝部分切除术后肝再生过程。     

藏红花对肝纤维化大鼠肝脏组织中Caspase-3，Bcl-2 表达的影响

目的:研究藏红花(Saffron)对肝纤维化大鼠肝组织中半胱氨酸天冬氨酸蛋白酶-3(Caspase-3),B细胞淋巴瘤/白血病-2(Bcl-2)表达的影响。方法:45只雄性SD大鼠随机均分为3组:正常组、模型组、藏红花组,除正常组外,另外两组给予40%四氯化碳橄榄油溶液腹腔注射制备肝纤维化大鼠模型,在造模的同时,藏红花组给予藏红花溶液5 m L·kg~(-1)·d~(-1)灌胃。8周后处死大鼠,留取肝脏组织,通过Masson染色观察大鼠肝纤维化的形成,免疫组化方法检测肝组织中Caspase-3及Bcl-2蛋白表达。结果:模型组大鼠肝纤维化程度最重,藏红花组较模型组纤维化程度轻,正常组大鼠肝脏无纤维化。与模型组比,藏红花组Caspase-3在肝实质内呈弱阳性表达,而纤维间隔内表达增加;Bcl-2的表达明显减少(P0.05),正常组Caspase-3及Bcl-2几乎无表达。结论:藏红花具有抗肝纤维化作用,其机制可能与调节Caspase-3,Bcl-2的表达有关。     

A trans10-18:1 enriched fraction from beef fed a barley grain-based diet induces lipogenic gene expression and reduces viability of HepG2 cells

Beef fat is a natural source of trans (t) fatty acids, and is typically enriched with either t10-18:1 or t11-18:1. Little is known about the bioactivity of individual t-18:1 isomers, and the present study compared the effects of t9-18:1, cis (c)9-18:1 and trans (t)-18:1 fractions isolated from beef fat enriched with either t10-18:1 (HT10) or t11-18:1 (HT11). All 18:1 isomers resulted in reduced human liver (HepG2) cell viability relative to control. Both c9-18:1 and HT11were the least toxic, t9-18:1had dose response increased toxicity, and HT10 had the greatest toxicity (P<0.05). Incorporation of t18:1 isomers was 1.8–2.5 fold greater in triacylglycerol (TG) than phospholipids (PL), whereas Δ9 desaturation products were selectively incorporated into PL. Culturing HepG2 cells with t9-18:1 and HT10 increased (P<0.05) the Δ9 desaturation index (c9–16:1/16:0) compared to other fatty acid treatments. HT10 and t9-18:1 also increased expression of lipogenic genes (FAS, SCD1, HMGCR and SREBP2) compared to control (P<0.05), whereas c9-18:1 and HT11 did not affect the expression of these genes. Our results suggest effects of HT11 and c9-18:1 were similar to BSA control, whereas HT10 and t-9 18:1 (i.e. the predominant trans fatty acid isomer found in partially hydrogenated vegetable oils) were more cytotoxic and led to greater expression of lipogenic genes.     

Mapping and analyzing the human liver proteome: progress and potential

Introduction: The liver is an important organ in humans. Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world. Progress in the Human Liver Proteome Project (HLPP) has improved understanding of the liver and the liver cancer proteome.

Areas covered: Here, we summarize the recent progress in liver proteome modification profiles, proteomic studies in liver cancer, proteomic study in the search for novel liver cancer biomarkers and drug targets, and progress of the Chromosome Centric Human Proteome Project (CHPP) in the past five years in the Institutes of Biomedical Sciences (IBS) of Fudan University.

Expert commentary: Recent advances and findings discussed here provide great promise of improving the outcome of patients with liver cancer.     

参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎的临床疗效

目的:探讨参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎的临床疗效及对肝功能和炎症指标的影响。方法:选择2014年3月至2015年8月在我院接受治疗的120例急性酒精中毒伴吸入性肺炎患者为研究对象,按照随机数字表法分为治疗组和对照组,每组60例患者,对照组给予布地奈德治疗,治疗组在对照组的基础上给予参麦注射液治疗,观察两组患者的临床疗效、症状消失时间、肝功能及血清肿瘤坏死因子-α、IL-6和IL-8炎性细胞因子的变化。结果:治疗组的总有效率为95.00%显著高于对照组的83.00%,差异有统计学意义(X~2=-4.227,P=0.039)。治疗组的哮鸣音、湿罗音、咳嗽和气喘消失时间明显短于对照组,差异有统计学意义(P0.005)。治疗组的肝功能ALT、AsT和GGT明显改善,炎性因子TNF-α、IL-6和IL-8水平下降明显,差异均有统计学意义(P0.005)。结论:参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎疗效确切,可以有效缩短患者的症状消失时间,改善肝功能,减轻炎症反应,值得临床推广应用。     

PTVE 与TIPS治疗肝硬化门静脉高压合并食管胃底静脉曲张破裂出血 的疗效比较

目的:研究经皮胃底曲张静脉栓塞术(PTVE)和经颈静脉肝内门体分流术(TIPS)治疗肝硬化门静脉高压合并食管胃底静脉曲张破裂出血的临床疗效,为临床治疗提供依据。方法:选取2001年4月到2015年4月我院肝硬化门静脉高压合并食管胃底静脉曲张破裂患者169例,根据手术方式分为PTVE组(行PTVE治疗)141例和TIPS组(行TIPS治疗)28例,比较两组术前、术后门静脉压力,术前、术后3个月、6个月以及1年两组Child-Pugh评分、白蛋白以及直接胆红素,并比较两组再出血和肝性脑病发生率。结果:TIPS组术后门静脉压力较术前显著降低,比较差异具有统计学意义(P0.05),术后PTVE组及TIPS组组间比较差异具有统计学意义(P0.05);两组术前和术后各时间直接胆红素无统计学意义(P0.05);PTVE组术后1年白蛋白水平显著升高,与术前和TIPS组比较差异具有统计学意义(P0.05),TIPS组术后白蛋白有所升高,但各时间比较差异无统计学意义(P0.05),PTVE组术后各时间Child-Pugh评分较术前明显改善,比较差异具有统计学意义(P0.05),TIPS组术后3个月和术后6个月Child-Pugh评分较术前明显改善,比较差异具有统计学意义(P0.05);两组术后再出血发生率比较无统计学意义(P0.05),PTVE组肝性脑病发生率显著低于TIPS组,比较差异具有统计学意义(P0.05)。结论:PTVE和TIPS治疗肝硬化门静脉高压合并食管胃底静脉曲张破裂出血效果相当,TIPS能显著降低门静脉压,PTVE能降低肝性脑病的发生率,改善患者Child-Pugh评分。     

自噬在肝脏蛋白质和脂质代谢中的作用

自噬是一个通过降解细胞组分如细胞器和蛋白质等以维持细胞存活和功能的重要的溶酶体途径。肝脏作为新陈代谢的中枢器官,肝脏高度依赖于自噬以发挥正常功能并防止疾病发展。肝细胞自噬的改变参与肝损伤,脂肪肝等肝病的病理变化,以自噬为靶点寻求治疗各种肝病的方法已成为热点研究领域,但自噬在肝脏蛋白质和脂质代谢中的作用极其机制尚不清楚。本文对自噬在肝脏蛋白质和脂质代谢中的作用的最新进展进行综述。     

Negative regulation of the hepatic fibrogenic response by suppressor of cytokine signaling 1

Suppressor of cytokine signaling 1 (SOCS1) is an indispensable regulator of IFNγ signaling and has been implicated in the regulation of liver fibrosis. However, it is not known whether SOCS1 mediates its anti-fibrotic functions in the liver directly, or via modulating IFNγ, which has been implicated in attenuating hepatic fibrosis. Additionally, it is possible that SOCS1 controls liver fibrosis by regulating hepatic stellate cells (HSC), a key player in fibrogenic response. While the activation pathways of HSCs have been well characterized, the regulatory mechanisms are not yet clear. The goals of this study were to dissociate IFNγ-dependent and SOCS1-mediated regulation of hepatic fibrogenic response, and to elucidate the regulatory functions of SOCS1 in HSC activation. Liver fibrosis was induced in Socs1^−/−Ifng^−/− mice with dimethylnitrosamine or carbon tetrachloride. Ifng^−/− and C57BL/6 mice served as controls. Following fibrogenic treatments, Socs1^−/−Ifng^−/− mice showed elevated serum ALT levels and increased liver fibrosis compared to Ifng^−/− mice. The latter group showed higher ALT levels and fibrosis than C57BL/6 controls. The livers of SOCS1-deficient mice showed bridging fibrosis, which was associated with increased accumulation of myofibroblasts and abundant collagen deposition. SOCS1-deficient livers showed increased expression of genes coding for smooth muscle actin, collagen, and enzymes involved in remodeling the extracellular matrix, namely matrix metalloproteinases and tissue inhibitor of metalloproteinases. Primary HSCs from SOCS1-deficient mice showed increased proliferation in response to growth factors such as HGF, EGF and PDGF, and the fibrotic livers of SOCS1-deficient mice showed increased expression of the Pdgfb gene. Taken together, these data indicate that SOCS1 controls liver fibrosis independently of IFNγ and that part of this regulation may occur via regulating HSC proliferation and limiting growth factor availability.     

肝切除手术治疗肝包虫病的疗效及对患者预后和肝功能的影响

目的:探讨肝切除手术治疗肝包虫病的疗效及对患者预后和肝功能的影响。方法:选取2015年2月-2018年5月期间我院收治的肝包虫病患者103例为研究对象,所有患者根据手术方式的不同分为A组(n=51,行外膜内完整外囊摘除术)和B组(n=52,行肝切除手术),比较两组患者围术期临床指标、肝功能指标、并发症发生情况,随访半年,记录两组患者随访期间死亡及原位复发情况。结果:B组术中出血量少于A组,手术时间、术后拔管时间以及住院时间均短于A组,组间比较差异有统计学意义(P0.05)。与术前比较,两组患者术后3 d、术后7 d谷丙转氨酶、胆红素以及谷草转氨酶均升高,但B组低于A组(P0.05);与术前比较,两组患者术后3 d、术后7 d白蛋白降低,但B组高于A组(P0.05);与术后3 d比较,两组患者术后7d谷丙转氨酶、胆红素以及谷草转氨酶均降低,白蛋白升高(P0.05)。B组术后并发症总发生率为7.69%(4/52),低于A组的23.52%(12/51),组间比较差异有统计学意义(P0.05)。两组随访期间无患者死亡,原位复发率比较差异均无统计学意义(P0.05)。结论:肝切除手术治疗肝包虫病患者安全有效,可减少术中出血量,促进患者术后康复,减轻手术对肝功能的影响,且术后复发率较低,患者预后较好。     

覆膜支架腔内修复术与药物保守治疗对Stanford B型主动脉夹层动脉瘤患者肝肾功能、炎性因子以及预后的影响

目的:比较覆膜支架腔内修复术与药物保守治疗对Standford B型主动脉夹层动脉瘤的疗效及对患者肝肾功能、炎性因子及预后的影响。方法:选择2012年1月～2014年8月我院收治的Standford B型主动脉夹层动脉瘤患者68例,按照随机数字表法分为对照组与研究组,各34例。对照组入院后采取药物保守治疗,研究组应用覆膜支架腔内修复术治疗。观察两组住院期间死亡率、再次手术或介入率以及治疗前、治疗2周后肝肾功能、血清炎性因子变化。所有患者随访36个月,比较两组患者预后情况。结果:研究组再次手术或介入率为2.94%,低于对照组的22.58%(P0.05)。治疗2周后,研究组丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、尿素氮(BUN)、肌酐(Cr)、胱抑素C、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、γ-干扰素(INF-γ)、C反应蛋白(CRP)水平较治疗前降低(P0.05),且研究组低于对照组(P0.05)。两组患者均随访36个月,随访12个月时两组患者生存率分别为100.00%和80.65%,随访36个月时两组患者生存率分别为91.18%和29.03%,经Log Rank分析显示,两组生存率比较差异有统计学意义(P0.05)。结论:覆膜支架腔内修复术治疗Standford B型主动脉夹层动脉瘤的疗效确切,能够改善患者肝肾功能,降低炎症反应,患者近中期随访生存率较高,其效果优于保守治疗。