芒硝外敷联合乌司他丁对胰腺炎大鼠肠屏障功能、胰腺细胞活性及PI3K/Akt/mTOR信号的影响

目的探讨芒硝外敷联合乌司他丁对胰腺炎大鼠肠屏障功能、胰腺细胞活性及PI3K/Akt/mTOR信号的影响。方法选取50只SPF级SD雄性大鼠,随机分为正常(N)组,模型(M)组,芒硝外敷(G)组,乌司他丁(U)组,芒硝外敷+乌司他丁(O)组,每组10只,对M组、G组、U组、O组采用开腹经胰胆管逆行性注射5%牛黄胆酸钠法建立胰腺炎模型,N组不建立该模型,建模成功后,对G组腹部给予芒硝外敷,对U组腹腔注射乌司他丁5万U/kg,对O组腹部给予芒硝外敷和腹腔注射乌司他丁5万U/kg,N组、M组同期给予腹腔注射同体积生理盐水,HE法检测胰腺组织病理形态,电镜检测肠屏障功能,TUNEL法检测胰腺细胞凋亡,免疫印迹法检测PI3K/Akt/mTOR信号相关蛋白表达。结果与N组相比,M组可见胰腺组织明显病理变化及肠屏障功能损伤,与M组比较,G组、U组、O组病理形态及肠屏障功能明显改善,且O组改善最为明显;与N组相比,M组大鼠肠粘膜损伤程度、胰腺组织中PI3K、p-Akt、p-mTOR蛋白表达显著升高,胰腺细胞凋亡水平显著降低(均P<0.05),与M组比较,G组、U组、O组大鼠肠粘膜损伤程度、胰腺组织中PI3K、p-Akt、p-mTOR蛋白表达显著降低(均P<0.05),胰腺细胞凋亡水平显著升高(P<0.05),且U组与G组相比差异无统计学意义(P>0.05),O组比U组变化明显(P<0.05)。结论芒硝外敷联合乌司他丁可显著改善胰腺炎大鼠肠屏障功能及胰腺细胞活性,并显著抑制PI3K/Akt/mTOR信号。

新型1H-吡咯[2,3-c]并吡啶衍生物的合成和抗胰腺癌活性评价

胰腺癌恶性程度高、治疗药物少,开发具有抗胰腺癌活性的化合物有重要研究意义。通过改造1H-吡咯[2,3-c]并吡啶的氮1位,合成了22个化合物,对所有化合物的抗胰腺癌活性进行了评价,II-1活性表现较为突出(半抑制浓度IC50=3.61μmol/L)。利用细胞划痕实验及侵袭实验对II-1的抗迁移能力及侵袭能力进行了研究。经1、5、10μmol/L的II-1处理24 h时,与对照组相比胰腺癌细胞(PANC-1细胞)迁移率分别下降28%、41%、54%;经1、5、10μmol/L的II-1处理48 h时,与对照组相比PANC-1迁移率分别下降25%、46%、49%;经1、5、10μmol/L的II-1处理48 h时,与对照组相比PANC-1细胞相对侵袭能力分别下降64%、79%、89%。实验结果表明:II-1对PANC-1细胞具有较高的抑制活性,II-1抑制PANC-1细胞迁移及侵袭能力也较为突出。

黄芪多糖对肉仔鸡生长性能和脏器指数及胰腺消化酶活性的影响

为探明黄芪多糖对肉仔鸡生长性能、脏器指数及胰腺消化酶活性的影响,选用1日龄健康艾维茵肉仔鸡256只,随机分为4组,分别饲喂含0、0.2%、0.4%和0.6%黄芪多糖的基础日粮(分别记为CK和A、B、C组),饲养期为14 d。结果表明,①添加黄芪多糖对7日龄和14日龄肉仔鸡的日增重、日采食量及料重比等生长性能指标的影响不显著(P>0.05)。②添加黄芪多糖对7日龄肉仔鸡肝脏指数和胰腺指数的影响明显(各试验组均高于对照组;B组的肝脏指数和胰腺指数与对照差异显著,C组的胰腺指数与对照差异极显著;B、C组的胰腺指数极显著高于A组),但对14日龄的影响处理间差异不显著。③各试验组的胰腺脂肪酶活性和胰腺蛋白酶活性均高于对照组:对于7日龄仔鸡,C组的胰腺蛋白酶活性显著高于对照组,且显著高于A组和B组;C组的胰腺脂肪酶活性极显著高于对照组和A、B组;对于14日龄仔鸡,各试验组的脂肪酶活性均极显著高于对照组,且C组显著高于A组和B组。添加黄芪多糖对7日龄和14日龄肉仔鸡胰腺淀粉酶活性的影响差异不显著。综合考虑,以0.6%黄芪多糖添加量较适宜,但其对肉仔鸡生长性能的影响不大。

一氧化氮的胰腺保护作用与胰腺组织磷脂酶A_2活性的关系

为探讨内源性一氧化氮(NO)对实验性急性坏死性胰腺炎的作用及其与胰腺组织磷脂酶A_2(PLA_2)活性的关系,以5％牛磺胆酸钠溶液胰胆管注射(1mL/kg)制成大鼠急性坏死性胰腺炎模型,以L-硝基精氨酸(L-NNA)为内源性NO的阻断剂,观察内源性NO对胰腺损伤程度和胰腺组织PLA_2活性的影响。发现牛磺胆酸钠胰胆管注射可造成胰腺组织明显的水肿和坏死,部分大鼠发生胰腺实质内出血,但胰腺组织内PLA_2的活性并没有显著变化。以L-NNA阻断内源性NO明显加重胰腺损伤,却对胰腺组织局部的PLA_2活性没有影响。结果提示:内源性NO具有胰腺保护作用,但其保护作用可能与胰腺组织局部的PLA_2活性无关。

5例胰腺血管活性肠肽瘤患者的护理

总结5例胰腺血管活性肠肽瘤患者的护理,术前做好腹泻和低钾血症的护理,术后严密监测血糖和电解质变化,做好生物治疗、靶向治疗后不良反应的护理,促进患者康复。

吉西他滨对胰腺癌细胞PANC-1活性和蛋白表达的影响

目的:研究吉西他滨(健择,Gemcitabine,GEM)对胰腺癌细胞PANC-1活性及蛋白表达的影响。方法:应用噻唑蓝(MTT)比色法检测吉西他滨在不同时间(12h、24h、36h、48h)下对胰腺癌细胞PANC-1存活率的影响,透射电镜观察吉西他滨对胰腺癌细胞PANC-1形态的影响,蛋白印迹法观察经吉西他滨作用前后蛋白的表达。结果:吉西他滨对PANC-1细胞生长的抑制有时间依赖性,透射电镜观察胰腺癌细胞发生核质疏松,核膜分层、起泡甚至破裂,核质溢出,胞浆也出现空泡,细胞膜和细胞器发生明显改变,随而质膜渗透性增加并细胞溶解,蛋白印迹法显示,GEM影响蛋白质表达。结论:吉西他滨对胰腺癌细胞PANC-1的生长具有显著抑制作用。药物敏感性降低和作用时间延长能导致蛋白的表达及改变。

谷氨酰胺对特种野猪仔猪消化道发育及胰腺消化酶活性的影响

试验旨在研究饲料中添加不同水平的谷氨酰胺(glutamine,Gln)对50日龄特种野猪仔猪消化道及胰腺消化酶活性的影响。选取50日龄特种野猪160头,随机分为4个处理,每处理4个重复,每重复10头仔猪。对照组饲喂基础日粮,试验组分别在基础日粮中添加0.5%、1%、1.5%Gln,试验期为35 d。结果表明,与对照组相比,饲料中添加Gln对特种野猪仔猪各肠道肠体指数和肠长指数影响均不显著(P>0.05),Gln显著提高了胰腺指数和胰腺脂肪酶活性(P<0.05),对胰腺淀粉酶活性、胰腺糜蛋白酶活性和胰腺胰蛋白酶活性影响不显著(P>0.05)。因此,饲料中添加Gln增加了胰腺指数,在一定程度上提高了胰腺消化酶活性。

11例胰腺炎病人的护理体会

观察奥曲肽治疗胰腺炎的治疗与护理。方法:将奥曲肽0.1mg静脉推注后连续0.3mg+0.9%NS500ml静脉滴注24小时连续使用观察患者腹痛、腹胀缓解情况随时检查尿淀粉酶、血淀酶恢复正常时间,持续使用5-7天,直至血淀酶恢复正常值后再持续2-3天停止使用。结果:通过上述治疗患者腹痛、腹胀,血淀粉酶、尿淀粉恢复正常时间缩短期。结论:经临床正确治疗及合理护理,保证有效的药物治疗,效果极好。

胰腺小分子活性肽对H_2O_2诱导体外大鼠胰岛细胞凋亡的影响

目的研究胰腺小分子活性肽对H2O2诱导体外大鼠胰岛细胞凋亡的影响。方法采用胶原酶消化和组织培养法分离纯化大鼠胰岛细胞,检测其纯度与活性。对照组加入普通培养基,实验组培养基中加入不同质量浓度(100、200、300、400μg/ml)胰腺小分子活性肽,阳性对照组培养基中加入100nmol/L艾塞那肽。每组细胞做5个复孔(n=5),培养5d后每组均接受H2O2100μmmol/L处理1h。采用Hoechst33258核染色形态学观察;AnnexinV-FITC/PI双染色流式细胞仪检测各组细胞凋亡率;荧光定量PCR法检测bax、bcl-2及caspase3mRNA的表达;Western-bolt检测bax、bcl-2蛋白的表达。结果 300、400μg/ml胰腺小分子活性肽和阳性对照组胰岛细胞凋亡率小于对照组(P<0.05);300、400μg/ml胰腺小分子活性肽组胰岛细胞bcl-2蛋白表达高于对照组(P<0.05),bax与caspase3蛋白表达低于对照组(P<0.05);300、400μg/ml胰腺小分子活性肽组胰岛细胞bcl-2mRNA的表达高于对照组(P<0.05),且bax mRNA的表达低于对照组(P<0.05)。结论胰腺小分子活性肽在浓度为300、400μg/ml时对大鼠胰岛细胞凋亡有明显保护作用。

胰腺血管活性肠肽瘤临床特点和诊治

胰腺血管活性肠肽瘤(vasoactive intestinal peptide tumors,VlPoma)为罕见的胰腺内分泌肿瘤,有典型的临床表现,如水样腹泻、低钾血症、胃酸缺乏。胰体尾部是病变的主要部位。临床筛查,早期诊断,恰当的处理方式,可影响病人的存活率并提高生存质量。典型症状和血浆血管活性肠肽(vasoactive intestinal polypeptide,VIP)值是诊断的关键。手术切除是最佳的治疗方式。药物治疗首选生长抑素类似物,可以使疾病症状(即使是未行手术者)长期缓解。

红树老鼠簕来源内生青霉 Penicillium sp.GXIMD 03101的次级代谢产物研究

为了研究红树老鼠簕Acanthus ilicifolius L.来源内生青霉Penicillium sp.GXIMD 03101的次级代谢产物,采用硅胶柱层析、凝胶柱层析及半制备高效液相色谱对大米发酵产物进行分离纯化,利用核磁共振方法鉴定化合物的结构,并对化合物1-4进行抗胰腺癌活性筛选。结果显示,从内生青霉Penicillium sp.GXIMD 03101中分离鉴定出13个化合物,分别为(+)-rugulosin A(1)、(+)-rugulosin B(2)、1,1′,3,3′,5,5′-hexahydroxy-7,7′-dimethyl[2,2′-bianthracene]-9,9′,10,10′-tetraone(3)、questin(4)、emodin(5)、questinol(6)、uridine(7)、2′-deoxythymidine(8)、5′-O-acetyl uridine(9)、ergosta-5,7,22-triene-3β-ol(10)、(3 R)-6-hydroxymellein(11)、6-hydroxy-8-methoxy-3,4-dimethylisocoumarin(12)和indole-3-acetic acid(13)。其中,化合物1对胰腺癌细胞表现出较好的细胞毒活性,其浓度为10μmol/L时对胰腺癌细胞的抑制率为75.6%。以上结果为进一步研究开发红树内生青霉来源的天然抗胰腺癌药物提供了物质基础。

Therapy for acute pancreatitis with platelet-activating factor receptor antagonists

Acute pancreatitis (AP) causes release of platelet- activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R). Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of PAF-RA show PAF- RAs significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.

Effect of biologically active fraction of Nardostachys jatamansi on cerulein-induced acute pancreatitis

AIM： To determine if the fraction of Nardostachysjata- mansi （N J） has the potential to ameliorate the severity of acute pancreatitis （AP）. METHODS： Mice were administered the biologically active fraction of N J, i.e., the 4th fraction （N J4）, intra- peritoneally, and then injected with the stable chole- cystokinin analogue cerulein hourly for 6 h. Six hours after the last cerulein injection, the pancreas, lung, and blood were harvested for morphological examination,measurement of cytokine expression, and examination of neutrophil infiltration. RESULTS： N J4 administration attenuated the sever- ity of AP and lung injury associated with AP. It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heine oxy- genase-1 （HO-1）. Furthermore, NJ4 and its biologically active fraction, N J4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pan- creatic acinar cells. CONCLUSION： These results suggest that N J4 may be a candidate fraction offering protection in AP and N J4 might ameliorate the severity of pancreatitis by induc- ing HO-1 expression.

Inhibitory effects of antisense phosphorothioate oligodeoxynucleotides on pancreatic cancer cell Bxpc-3 telomerase activity and cell growth in vitro

AIM： To investigate the effect of telomerase hTERT gene antisense oligonucleotide （hTERT-ASO） on proliferation and telomerase activity of pancreatic cancer cell line Bxpc-3. METHODS： MTT assay was used to detect the effect of different doses of hTERT-ASO on proliferation of Bxpc-3 cell for different times. To study the anti-tumor activity, the cells were divided into there groups： Control group （pancreatic cancer cell Bxpc-3）; antisense oligonucleotide （hTERT-ASO） group; and nosense oligonucleotide group decorated with phosphorothioate. Telomerase activity was detected using TRAP-PCR-ELISA. Cell DNA distribution was examined using flow cytometry assay. Cell apoptosis was observed by transmission electron microscope in each group. RESULTS： After treatment with 6 mmollL hTERT- ASO, cell proliferation was inhibited in dose- and time- dependent manner. The telomerase activity decreased after treatment with hTERT-ASO for 72 h. Flow cytometry showed the cell number of G0/G1 phase increased from 2.7% to 14.7%, the cell number of S phase decreased from 72.7% to 51.0%, and a sub-G1 stage cell apoptosis peak appeared in front of G1 stage. CONCLUSION： Telomerase antisense oligodeoxy- nucleotide can inhibit the proliferation of pancreatic cancer cell line Bxpc-3 and decrease the telomerase activity and increase cell apoptosis rate in vitro.

Effect of endothelin-1 receptor antagonists on histological and ultrastructural changes in the pancreas and trypsinogen activation in the early course of caerulein-induced acute pancreatitis in rats

AIM: To assess the effect of non-selective ETA/B (LU 302872)and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerulein-induced AP.METHODS: Male Wistar rats with caerulein-induced AP,lasting 4 h, were treated i.p. with 10 and 20 mg/kg b.w.of each antagonist. Edema, inflammatory infiltration,necrosis and vacuolization of acinar cells in the pancreas were scored at 0-3 scale. Free active trypsin (FAT), total potential trypsin (TPT) after activation with enterokinase,and index of trypsinogen activation (%FAT/TPT) were assayed in pancreatic homogenates.RESULTS: In untreated AP, the edema, inflammatory infiltration, necrosis and vacuolization increased as compared to control healthy rats (P＜0.01). None of the treatment exerted any meaningful effect on the edema and inflammatory infiltration. The selective antagonist increased slightly the necrosis score to 0.82±0.06 at higher dose (P＜0.05) vs 0.58±0.06 in untreated AP. The nonselective antagonist increased slightly the vacuolization score to 2.41±0.07 at higher dose (P＜0.01) vs 1.88±0.08in untreated AP. The decrease in the number of zymogen granules, disorganization of endoplasmic reticulum,autophagosomes and cytoplasmic vacuoles were more prominent in treated AP than in untreated AP groups.%FAT/TPT in untreated AP increased about four times (18.4±3.8 vs4.8±1.3 in control group without AP, P＜0.001).Treatment of AP with both antagonists did not affect significantly augmented trypsinogen activation.CONCLUSION: The treatment with endothelin-1 receptors (non-selective ETA/B and selective ETA) antagonists has essential effect neither on the edema and inflammatory infiltration nor on trypsinogen activation observed in the early course of caerulein-induced AP. Nevertheless a slight increase of the necrosis and vacuolization score and some of the ultrastructural data could suggest the possibility of their undesired effects in caerulein-induced AP at investigated doses.

Quality of life in chronic pancreatitis

In an era such as the present one in which there is a high demand for health services with the associated pressure of controlling spending, health care organizations are concerned about the cost-effectiveness of quality improvement interventions. On the other hand, the impact of the disease and the treatment on the patient’s overall well-being and functioning has become a topic of growing interest not only in clinical research but also in practice. The clinical evaluation of the benefits of specific treatments for chronic, debilitating and incurable diseases should increasingly include formal assessment of patient activity and well-being. Thus, health-related quality of life as subjectively perceived by the patient, is becoming a major issue in the evaluation of any therapeutic intervention, mainly in patients with chronic or difficult diseases where the aim of the intervention is to keep patients either symptom-free and capable of living in the community for a long time or to reduce the discomfort caused by the disease. In this paper, we review the current knowledge on the quality of life assessment in chronic pancreatitis patients.

Octreotide reverses shock due to vasoactive intestinal peptide-secreting adrenal pheochromocytoma: A case report and review of literature

Vasoactive intestinal peptide-producing tumors （VIP-oma） usually originate in the pancreas and are chara-cterized by diarrhea, hypokalemia, and achlorhydria （WDHA syndrome）. In adults, nonpancreatic VIPoma is very rare. Herein, we report an unusual case of VIP-producing pheochromocytoma marked by persistent shock, fushing, and watery diarrhea and high sensitivity to octreotide. A 53-year-old woman was hospitalized for sudden-onset hypertension with convulsions, which then rapidly evolved to persistent shock, fushing, and watery diarrhea. Abdominal computed tomography indicated a left adrenal mass, accompanied by bleeding;and marked elevations of both plasma catecholamine and VIP concentrations were documented via laboratory testing. Surprisingly, all clinical symptoms responded swiftly to octreotide treatment. Once surgically treated, hormonal levels normalized in this patient, and the clinical symptoms dissipated. Postoperative pathological and immunohistopathological studies confrmed a VIP-secreting pheochromocytoma with strong, diffuse positivity for somatostatin receptor type 2. During a 6-mo follow-up period, she seemed in good health andwas symptom-free.

全身多发转移的胰腺血管活性肠肽瘤

胰腺血管活性肠肽瘤(VIPoma)为罕见的胰腺功能性神经内分泌肿瘤,临床表现为大量水样泻、严重低钾血症、无胃酸或低胃酸。该患者为胰腺VIPoma伴全身多发转移,经外科手术切除、靶向药物等治疗后仍出现顽固性、周期性大量水样泻。经遵义医科大学附属医院神经内分泌肿瘤多学科诊疗团队诊治后,制订个体化诊疗方案,使用短效和长效生长抑素类似物(SSA)联同肝动脉栓塞术肝内减瘤控制功能性肿瘤激素分泌、抑制肿瘤生长的综合治疗后,患者显著获益,现报告其多学科诊治经过以供临床参考。

Physiological responses of Chinese longsnout catfish to water temperature

We evaluated the effect of water temperature on the growth and physiology of the Chinese longsnout catfish （Leiocassis longirostris Günther）. The fish were reared at four temperatures （20, 25, 30, and 35℃） and sampled on days 7, 20, and 30. We measured plasma levels of insulin, free thyroxine （FT4）, free 3,5,3＇-triiodothyronine （FT3）, lysozyme and leukocyte phagocytic activity. The optimum water temperature for growth was 27.7℃. The plasma levels of insulin and FT4 declined significantly （P〈0.05） on day 30 at temperatures above 20℃. Lysozyme activity was significantly （P〈0.05） lower at 25℃ than at other temperatures. We conclude that final weight, insulin, FT4, and lysozyme were significantly affected by water temperature.

Effects of tributyltin (TBT) on enzyme activity and oxidative stress in hepatopancreas and hemolymph of small abalone,Haliotis diversicolor supertexta

We investigated the effect of tributyltin (TBT) exposure on the concentration of malondialdehyde (MDA) and the activity levels of the superoxide dismutase (SOD),catalase (CAT),and acid and alkaline phosphatase (ACP and AKP) enzymes in the small abalone,Haliotis diversicolor supertexta.We collected samples of the hepatopancreas and hemolymph 2,6,24,48,96,and 192 h after exposure to 0.35 μg (Sn)/L TBT.In the hepatopancreas,ACP activity was significantly higher in animals exposed to TBT 2,24,and 96 h post-exposure compared with the control animals.AKP activity was also higher after 2 h,but SOD and CAT activity was unchanged.The concentration of MDA in the hemolymph was significantly higher than the control animals 2 and 6 h post-exposure.In the hemolymph of animals exposed to TBT,ACP activity was significantly lower than in the control animals 192 h post-exposure,whereas AKP activity was significantly lower 2 and 192 h post-exposure.Hemolymph SOD activity and levels of MDA were significantly lower than in the control animals 24 h after exposure but significantly higher after 96 h.Our results demonstrate that exposure to TBT cause rapid changes in ACP and AKP activity as well as altering the concentration of MDA in the hepatopancreas and hemolymph.SOD and CAT do not appear to be involved in the detoxification of TBT in the hepatopancreas of small abalone.