奥曲肽辅助十二指肠镜治疗急性水肿型胆源性胰腺炎疗效及对炎症反应的影响

目的:探讨奥曲肽辅助十二指肠镜治疗急性水肿型胆源性胰腺炎疗效及对炎症反应的影响。方法:选择急性水肿型胆源性胰腺炎患者100例,随机分为研究组与对照组各50例,两组患者均给予禁食、抗感染、营养支持、酶抑制剂治疗,对照组同期给予十二指肠镜治疗,研究组同期给予奥曲肽辅助十二指肠镜治疗,比较两组腹痛缓解时间,白细胞(WBC)、体温恢复正常时间,治疗前(T0)、治疗3d(T1)、治疗7d(T2)血、尿淀粉酶水平与炎症因子CRP、IL-6、TNF-α水平的变化。结果:(1)研究组腹痛缓解时间、WBC、体温恢复正常时间均较对照组明显缩短(P0.05);(2)两组患者T1、T2血、尿淀粉酶水平均较T0明显降低,且T2血、尿淀粉酶水平低于T1(P0.05),研究组T1、T2血、尿淀粉酶水平均低于对照组(P0.05);(3)两组T1、T2血清CRP、IL-6、TNF-α水平均较T0明显降低,且T2低于T1(P0.05),研究组T1、T2时血清CRP、IL-6、TNF-α水平均低于对照组(P0.05)。结论:奥曲肽辅助十二指肠镜治疗急性水肿型胆源性胰腺炎可提高早期治疗效果,减轻炎症反应。     

The probiotic bacterium Lactobacillus plantarum species 299 reduces intestinal permeability in experimental biliary obstruction

AIMS: Extrahepatic biliary obstruction is associated with the failure of intestinal barrier function, allowing bacteria and other substances from the intestine to enter the circulation and initiate a systemic inflammatory response, causing impairment of organ function. Probiotic bacteria have been shown to have beneficial effects on intestinal barrier function in other conditions, but their effects have never been studied in biliary obstruction. Methods and Results: This study examined the effects of enteral administration of Lactobacillus plantarum species 299 (LP299) in oatmeal fibre compared with sterile oatmeal fibre in water or water alone in an animal model of biliary obstruction. Administration of LP299 was associated with reduced intestinal permeability compared with sterile oatmeal alone (0.262 +/- 0.105%vs 0.537 +/- 0.037%, P=0.019, percentage excretion of (14)Carbon), but there was no evidence of reduced endotoxin exposure or blunting of the systemic inflammatory response. Animals receiving sterile oatmeal fibre alone also failed to develop the hyperpermeability after biliary obstruction seen in animals receiving water only (0.512+/- 0.05%vs 0.788 +/- 0.18%), suggesting that oatmeal itself may have some beneficial effects on intestinal barrier function. Conclusion: Enteral administration of the probiotic bacterium LP299 reduces intestinal hyperpermeability associated with experimental biliary obstruction. Significance and Impact of the Study: This study provides insight to direct further work into the modulation of intestinal barrier function by probiotic bacteria.     

Stereoselectivity of biliary excretion of 2-arylpropionates in rats

To examine the stereoselectivity of biliary excretion, the optically pure enantiomers of ketoprofen (KT), ibuprofen (IBU), and flurbiprofen (FLU) were intravenously administered to normal and bile duct-cannulated rats at 10 mg/kg. The recovery of total KT in bile was significantly higher after administration of (S)-KT than after (R)-KT [90.1 ± 3.5% vs 68.8 ± 8.2%, n =3, P < 0.05]. In normal rats the terminal half-life of (R)-KT was significantly shorter than that of (S)-KT after administration of (R)-KT (2.2 ± 0.6 h vs 14.3 ± 4.9 h, n = 3, P < 0.05). The terminal half-life of both enantiomers was significantly shorter in rats with continuous bile drainage as compared to normal rats. No significant differences in pharmacokinetic parameters could be found between both enantiomers in bile duct-cannulated animals. The total amount of IBU in bile was slightly higher after administration of (S)-IBU than after (R)-IBU administration. The percentage of (R)-IBU after (R)-IBU administration, however, was very low [(R)-IBU: 1.5 ± 0.9%, (S)-IBU: 23.4 ± 5.8%]. In normal rats the clearance of (R)-IBU was significantly higher as compared to (S)-IBU. Differences in pharmacokinetic parameters between normal and bile duct-cannulated rats were not statistically significant due to high interindividual variability. The total recovery of FLU, which was excreted in bile to a lower extent than either KT or IBU, also tended to be greater after S-enantiomer administration. Only small amounts of (S)-FLU could be recovered in bile after (R)-FLU administration. The pharmacokinetic parameters did not differ significantly between (R)- and (S)-FLU or between normal and bile duct-cannulated rats due to its low inversion rate and low excretion via bile. © 1993 Wiley-Liss, Inc.     

原发性胆汁性肝硬化患者血清IL-6 水平与UDCA疗效的相关性研究

目的:观察原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者治疗前后血清IL-6表达水平,探索其与熊去氧胆酸(Ursodeoxycholic acid,UDCA)疗效的临床相关性。方法:本研究回顾性纳入自2013年-2015年就诊于第四军医大学西京消化病医院的40例新诊断PBC患者,及40例健康对照者。收集PBC患者治疗前后的相关临床资料和血清样本,采用ELISA方法检测患者血清IL-6表达水平,并进一步分析其临床意义。结果:1)治疗前PBC患者血清IL-6表达水平明显高于健康对照者(P0.001);2)PBC患者在接受UDCA治疗后的第3,6和12个月血清IL-6水平与治疗前相比明显降低(P0.05),且在第3个月时下降最明显。3)无论是依据Paris I标准还是Barcelona标准,结果显示,UDCA应答者与应答不佳者相比其治疗前血清IL-6水平无统计学差异(P=0.373;P=0.409)。但UDCA应答者在治疗3个月时其血清IL-6表达水平比治疗前明显下降(P0.05),而应答不佳者治疗3个月时血清IL-6表达水平与治疗前相比无明显差异(P=0.667;P=0.186)。结论:IL-6可能在PBC发病的免疫机制中发挥着重要的作用。目前尚不能认为PBC患者治疗前血清IL-6表达水平能独立评价UDCA疗效,但是治疗三个月后患者血清IL-6水平下降趋势能够提示PBC患者对UDCA的应答情况。     

经胰管预切开与双导丝技术在困难胆管插管中的插管效果及安全性对比

目的:比较经胰管预切开与双导丝技术在困难胆管插管中的插管效果及安全性。方法:收集我院2017年1月～2018年12月收治的60例经内镜逆行性胰胆管造影术、反复进入胰管的困难胆管插管患者,将患者按照入院先后顺序分为观察组和对照组,每组30例。两组患者分别经胰管预切开及双导丝技术辅助插管,对两组患者插管时间、插管成功率以及并发症的发生情况进行综合评价。结果:观察组患者插管时间短于对照组(P0.05),插管成功率为96.7%,显著高于对照组(73.3%,P0.05)。观察组和对照组患者并发症的发生率分别为10.0%、13.3%,组间差异无统计学意义(P0.05)。结论:对困难胆管插管患者,采用经胰管预切开的方式辅助插管操作简单,插管时间短,成功率高,且不增加并发症发生率。     

The role of ERK-RSK signaling in the proliferation of intrahepatic biliary epithelial cells exposed to microcystin-leucine arginine

Microcystin-leucine arginine (MC-LR) is a potent specific hepatotoxin produced by cyanobacteria in diverse water systems, and it has been documented to induce liver injury and hepatocarcinogenesis. However, its toxic effects on intrahepatic biliary epithelial cells have not been invested in detail. In this study, we aimed to investigate the effects of MC-LR exposure on the intrahepatic biliary epithelial cells in the liver. MC-LR was orally administered to mice at 1 μg/L, 7.5 μg/L, 15 μg/L, or 30 μg/L for 180 consecutive days for histopathological and immunoblot analysis. We observed that MC-LR can enter intrahepatic bile duct tissue and induce hyperplasia of mice. Human primary intrahepatic biliary epithelial cells (HiBECs) were cultured with various concentrations of MC-LR for 24 h, meanwhile the cell viability and proteins level were detected. Western blotting analysis revealed that MC-LR increased RSK phosphorylation via ERK signaling. RSK participated in cell proliferation and cell cycle progression. Taken together, after chronic exposure, MC-LR-treated mice exhibited abnormal bile duct hyperplasia and thickened bile duct morphology through activating the ERK-RSK signaling. These data support the potential toxic effects of MC-LR on bile duct tissue of the liver.     

Development of liver microtissues with functional biliary ductular network

Liver tissue engineering aims to create transplantable liver grafts that can serve as substitutes for donor's livers. One major challenge in creating a fully functional liver tissue has been to recreate the biliary drainage in an engineered liver construct through integration of bile canaliculi (BC) with the biliary ductular network that would enable the clearance of bile from the hepatocytes to the host duodenum. In this study, we show the formation of such a hepatic microtissue by coculturing rat primary hepatocytes with cholangiocytes and stromal cells. Our results indicate that within the spheroids, hepatocytes maintained viability and function for up to 7 days. Viable hepatocytes became polarized by forming BC with the presence of tight junctions. Morphologically, hepatocytes formed the core of the spheroids, while cholangiocytes resided at the periphery forming a monolayer microcysts and tubular structures extending outward. The spheroids were subsequently cultured in clusters to create a higher order ductular network resembling hepatic lobule. The cholangiocytes formed functional biliary ductular channels in between hepatic spheroids that were able to collect, transport, and secrete bile. Our results constitute the first step to recreate hepatic building blocks with biliary drainage for repopulating the whole liver scaffolds to be used as transplantable liver grafts.