大鼠急性坏死性胰腺炎脂质代谢的研究

目的 观察大鼠急性坏死性胰腺炎时血脂的代谢及其对炎症的影响.方法 36只SD大鼠(250 g左右),随机分为对照组和急性坏死性胰腺炎(ANP)3 h、6 h、12 h、24 h、48 h组,每组6只.除对照组外予胰管内逆行注射5%牛磺胆酸钠复制ANP大鼠模型,观察胰腺组织病理学和透射电镜的改变.检测各组血清淀粉酶、胆固醇、三酰甘油(TG)、游离脂肪酸(FFA)和脂蛋白脂酶(LPL)含量.RT-PCR检测硬脂酰基辅酶A脱氢酶1(SCD1)和脂肪酸转移酶(CD36)mRNA的表达.结果 血清淀粉酶和胰腺病理学改变符合大鼠ANP改变特征,在12 h组淀粉酶和胰腺病理学改变达峰值.电镜下ANP各组腺泡细胞粗面内质网扩张、酶原颗粒增多.ANP各组血清TG和FFA水平较对照组增高,其中ANP 24 h组TG为(0.81 ± 0.35)mmol/L,与对照组差异显著(P ＜0.01);ANP 6 h组FFA为(1.32 ± 0.32)mmol/L,较对照组显著升高(P ＜0.05).但ANP组LPL活性较对照组下降,胰腺组织SCD1 mRNA和CD36 mRNA表达升高.结论 ANP大鼠出现血脂增高、脂质代谢相关酶表达异常、胰腺腺泡细胞内质网扩张等方面改变,提示ANP可诱发机体脂质代谢紊乱.     

脂酶对实验性高脂血症性急性坏死性胰腺炎的影响

目的 探讨脂蛋白脂酶(LPL)和肝脂酶(HL)对实验性高脂血症性急性坏死性胰腺炎(HLANP)的影响.方法 通过高脂饲料喂养4周,胆胰管内逆行注射5%牛磺胆酸钠溶液诱导大鼠HLANP模型.72只大鼠按数字随机法分为HLANP组和急性坏死性胰腺炎(ANP)对照组,每组又分为造模后0、3、6、12、24、48 h 6个时间点,每个时间点6只.榆测血清淀粉酶、胆固醇、三酰甘油(TG)、游离脂肪酸(FFA)、LPL和HL水平;观察胰腺组织病理学和超微结构改变;RT-PCR检测胰腺HL mRNA表达;免疫组化方法检测胰腺HL蛋白表达.结果 HLANP组和对照组大鼠血清淀粉酶在12 h达峰值,均值分别为7 176 U/L和6 366 U/L,较基础水平显著升高(P<0.05);HLANP组0～12 h的血清胆固醇水平均高于相应时问点的对照组(P<0.05或P<0.01),TG仅0 h点两组相差显著(P<0.05),分别为(1.19±0.49)mmoi/L和(0.32±0.14)mmol/L;HLANP组FFA水平与对照组无显著差异;HLANP3 h组大鼠血清LPL和HL活性分别为(17.5±7)U/L和(18.6±3.9)U/L,显著高于对照组的(8.9±3.4)U/L和(9.5±2.1)U/L(P<0.05).HLANP组大鼠3、6、24、48 h的胰腺组织坏死程度均显著高于同时点对照组(P<0.05);HLANP组大鼠胰腺腺泡细胞出现脂滴沉积、粗而内质网扩张、酶原颗粒减少和线粒体肿胀.HLANP 3、6 h组大鼠胰腺HL mRNA表达分别为1.1±0.09和0.89±0.08,均显著高十对照组的0.1l 4-0.01和0.15±0.03(P<0.05);HLANP组和对照组大鼠胰腺腺泡细胞在ANP前未见HL蛋白表达,诱导ANP后均可见HL蛋白强阳性表达.结论 HIANP大鼠脂酶(LPL和HL)的表达增高,其血清蛋白含量增高,导致脂质分解,加重ANP.LPL和HL可能是加重HLANP的最关键的脂质代谢酶之一.     

齐留通对急性坏死性胰腺炎大鼠中性粒细胞活化的影响

背景：5-脂氧合酶（5-LOX）是将花生四烯酸、亚油酸和其他多不饱和脂肪酸转变为具有生物活性的代谢产物如自三烯类的限速酶,从而影响细胞信号转导、结构和代谢。然而关于其在重症急性胰腺炎（SAP）中作用的研究尚少。目的：研究选择性5-LOX抑制剂齐留通对急性坏死性胰腺炎（ANP）大鼠中性粒细胞活化的作用。方法：将54只Sprague—Dawley大鼠随机分为假手术组、ANP组和齐留通组。以5％牛磺胆酸钠胰胆管逆行注射诱导ANP模型。各组大鼠分别于6h、12h和24h处死。行胰腺组织病理学评分,以酶联免疫吸附测定（ELISA）检测血清可溶性细胞间黏附分子-1（sICAM-1）、可溶性E-选择素（sE-选择素）和可溶性P-选择素（sP-选择素）水平．以免疫组化染色检测胰腺缉织ICAM-1、E-选择素和P-选择素的表达,常规方法检测胰腺组织髓过氧化物酶（MPO）活性和血清淀粉酶水平。结果：与假手术组相比,ANP组同时间点胰腺组织病理学评分、廊清sICAM-1、sE-选择素和sP-选择素水平、胰腺组织ICAM-1、E-选择素和P-选择素表达以及胰腺组织MPO活性和血清淀粉酶水平均显著增高（P＜0．05）。经齐留通预处理后,除外6h组的组织病理学评分,上述各项指标均较同时间点ANP组显著降低（P＜0．05）。结论：选择性5-LOX抑制剂齐留通能通过抑制中性粒细胞活化而有助于减轻ANP大鼠胰腺组织学损伤。     

急性胰腺炎大鼠二十碳烯酸代谢的变化及PGE1对其的影响

目的了解大鼠急性出血坏死性胰腺炎（ANP）不同时相血清PGE2、PGF1α、TXB2等变化规律，以及这些变化与胰腺病理积分之间的相关性。研究外源性PGE1对上述代谢物变化的影响。方法实验用SD大鼠90只，随机分为对照组、ANP及PGE1治疗组。以3．5％牛磺胆酸钠经胰管内注射诱导大鼠实验性ANP，PGE1治疗组则于造模前及造模后1h腹腔内注射PGE1 3．0μg／kg体重。各组于造模舌第3h、6h、12h处死部分大鼠，取其血清及胰腺组织．分别检测血清淀粉酶．PGE2、PGF1α、TXB2浓度及胰腺病理评分，行相关性分析。结果与对照组相比．ANP组术后3h、6h、12h的淀粉酶、TXB2的血清浓度显著升高（P〈0．01），PGE2则显著下降（P〈0．05），PGF1α有所下降，但无统计学意义。PGE1治疗组，各时相淀粉酶、TXB2的血清浓度显著回落．与ANP组相应时相比较，有统计学意义（P〈0．01）．PGE2、PGF1α有所上升，但不显著。PGE1治疗组的胰腺出血、坏死积分显著低于ANP组．而水肿、白细胞浸润的积分无显著差别．相关性分析显示胰腺出血、坏死的积分与淀粉酶、TXB2等的血清浓度呈正相关。结论二十碳烯酸的异常代谢参与了ANP的发生、发展，外源性PGE1通过干预这种异常代谢，影响胰腺炎的发展。     

银杏苦内脂B对急性坏死性胰腺炎大鼠胰腺组织NF-kB p65、IkBαmRNA表达的影响

目的观察NF—kBp65、IkBαmRNA在急性坏死性胰腺炎（ANP）大鼠胰腺组织中的表达以及银杏苦内脂B（BN52021）对其表达的影响。方法180只Wistar大鼠随机分为对照组（NC组）、ANP模型组（ANP组）、BN52021治疗组（BN组），每组大鼠分别在术后1h、2h、3h、6h、12h和24h6个时间点处死，抽血测定血淀粉酶含量，取胰腺组织行病理学检查，RT—PCR法检测NF—kB p65、IkBαmRNA表达。结果血清淀粉酶和病理学改变符合ANP。BN52021能降低ANP大鼠的血清淀粉酶含量和改善胰腺的病理损害。ANP组和BN组NF—kB p65mRNA均呈双峰改变，第1峰在1h，第2峰分别在24h和12h，6h时降至最低。ANP组NF—kB p65mRNA表达在2h、3h、12h和24h较NC组显著增加（P〈0．05或0．001），仅在1h时较BN组有显著差异（P〈0．041），其他时间点无显著差异；但较NC组各时点显著升高（P〈0．05或0．001）。ANP组IkBαmRNA表达仅在24h点较NC组明显增加（P=0．000），BN组在1h、6h和12h较ANP组显著增加（P〈0．01），在1h、12h和24h也较NC组显著增加（P〈0．01）。结论NF—kBp65mRNA在ANP大鼠胰腺组织表达上调，IkBαmRNA仅在造模后24h时表达上调。BN52021可能通过上调IkBαmRNA的表达，破坏NF-kBp65mRNA和IkBαmRNA的平衡，从而发挥其治疗作用。     

急性坏死性胰腺炎大鼠血清消褪素的表达变化及意义

目的观察急性坏死性胰腺炎（ANP）大鼠血清消褪素D1（resolvin D1,RvD1）和白细胞介素-6（IL-6）、IL-10的变化情况,探讨RvD1在急性坏死性胰腺炎发病机制中的作用。方法70只SD大鼠随机分为ANP模型组（n=35）和假手术组（r／=35）。经十二指肠乳头逆行胆胰管注射4％牛磺胆酸钠来制备大鼠ANP模型。大鼠分别于造模后3h、6h、12h、24h、48h处死,测定大鼠血清淀粉酶,光镜下进行胰腺病理学观察及评分,应用酶联免疫吸附测定（ELISA）法检测血清RvD1和IL-6、IL-10的变化情况。结果ANP组大鼠血清淀粉酶从造模后3h开始升高,6h达峰值（8244．00±2949．83）u／L,各时点血清淀粉酶显著高于假手术组（P〈0．05）;ANP组胰腺病理损伤及评分于造模后3h～24h随时间延长逐渐加重,24h评分为（11．91±1．312）分,均较假手术组高（P〈0．05）。ANP组血清RvD1水平于造模后3h～24h随时间延长逐渐升高,24h达峰值（39．48±15．28）pg／mL,较假手术组显著升高（P〈0．05）,并与血清IL-6水平呈正相关（r=0．362,P〈0．05）;在造模后6h、12h、24h,ANP组的血清IL-6水平均较假手术组高（P〈0．05）,并随时间延长逐渐升高,于24h达峰值（1293．26±428．12）pg／mL;在造模后3h、24h和48h,ANP组的血清IL-10水平均较假手术组显著升高（P〈0．05）。结论血清Rv的变化可能与急性胰腺炎（AP）严重程度有关,在AP中起抗炎及促进炎性反应消退的作用。     

急性坏死性胰腺炎模型大鼠血清脂联素表达水平及意义

目的观察急性坏死性胰腺炎模型大鼠血清脂联素表达变化及与胰腺损伤程度的相关性在急性坏死性胰腺炎发病中的意义。方法40只雄性Sprague-Dawley大鼠随机分为正常对照组(CON组)8只及急性坏死性胰腺炎组(ANP组)32只。CON组剖腹后只翻动十二指肠及胰腺后关腹。ANP组逆行胰胆管内注射1.5%去氧胆酸钠制备ANP模型。术后6、12、24、48 h处死大鼠,观察胰腺组织病理改变并评分,检测血清淀粉酶、脂联素、TNF-α和IL-6水平变化。结果 ANP组大鼠胰腺病理学评分及血清淀粉酶、TNF-α、IL-6水平均较CON组升高(P<0.05),血清脂联素在发病早期下降缓慢,24 h后迅速下降,48 h较24 h显著降低(P<0.01),并与胰腺病理学评分及TNF-α水平呈高度负相关(r=-0.846、-0.789,P<0.05)。结论血清脂联素在ANP发生发展中呈现一定的变化规律,并且与胰腺严重程度呈负相关,可能在ANP的发病机制中起重要作用。     

山楂叶提取物对非酒精性脂肪性肝病大鼠糖脂代谢作用的研究

目的：观察山楂叶提取物对非酒精性脂肪性肝病（NAFLD）大鼠糖脂代谢的影响。方法：用高脂饲料诱导建立大鼠NAFLD模型,分为正常组、模型组、阳性药物对照组、山楂叶提取物组、自然恢复组和节食组,观察各组大鼠血清中甘油三酯（TC）,总胆固醇（TG）,游离脂肪酸（FFA）,脂蛋白酯酶（LPL）、空腹血糖（FBG）、空腹胰岛素（INS）和胰岛素抵抗指数（IRI）以及大鼠肝脏组织过氧化物酶体增殖物激活受体α（PPARα）mRNA的表达情况及其肝组织病理学改变情况。结果：与模型组和自然恢复组相比,山楂叶提取物组大鼠体重明显降低,血清TC、FFA、FPG、INS、IRI明显降低（P〈0．05）,同时LPL升高以及PPARαmRNA表达量升高亦有统计学意义（P〈0．05）。结论：山楂叶提取物能够改善NAFLD大鼠的糖脂代谢异常,这可能与提高LPL的含量和增加PPARctmRNA表达有关。     

大鼠急性胰腺炎时血液流变学和血流动力学改变的意义

目的：胰腺血运障碍是急性胰腺炎（AP）的发病原因之，全身血液流变学改变又与AP互为因果，探讨大鼠AP早期外周血流流变学和胰腺局部血流动力学的变化规律及两者的相关性具有一定的意义。方法：以牛磺胆酸钠诱导大鼠急性水肿性胰腺炎（AEP）模型（n=20）和急性坏死性胰腺炎（ANP）模型（n=20），另取10只正常大鼠作为对照。以多普勒超声诊断仪测定术前及术后胰腺局部血流速度，术后12h各组处死10只大鼠，检测外周血中各血液流变学指标，并观察胰腺组织的病理变化，两模型组其余10只大鼠观察3d内存活性情况。结果：AEP组大鼠仅外周血红细胞聚集指数较对照组升高，ANP大鼠所有血液流变学指标均较对照组升高，全血黏度曲线明显抬高。AEP和ANP组大鼠胰腺局部血流速度均明显减慢，分别降低至模前的79％和30％，光镜病理评分显示，AEP组水肿、炎症，出血和坏死评分均较对照有显著升高（P＜0．05），与AEP组比较，ANP组各项评分升高更明显（P＜0．05）。AEP组大鼠3d内存活率为90％，ANP组为0。结论：AP大鼠同时存在有全身血流变学和胰腺局部血流动力学改变。胰腺缺血引起的微循环障碍是AP的始动因素之一，血液流变学的变化并非AP的发病原因，但可以加重胰腺缺血，并对疾病发生后的胰腺损伤有促进作用。     

高三酰甘油血症对大鼠胰腺腺泡细胞的影响

目的研究高三酰甘油血症对大鼠胰腺腺泡细胞形态和功能的影响。方法断奶l周雄性SD大鼠（约70g）随机分为2组．每组10只．分别给予高脂饲料和普通饲料喂养4周。检测血清三酰甘油（TG）、胆固醇（TC）及游离脂肪酸（FFA）水平，HE染色和透射电镜观察胰腺腺泡细胞形态。胶原酶消化法分离大鼠胰腺腺泡细胞．台盼蓝染色测定细胞活力。给予不同浓度胆囊刺激素（CCK-8）刺激胰腺腺泡细胞分泌淀粉酶及乳酸脱氢酶（LDH）．测定酶释放率。结果高脂饮食饲喂大鼠4周后，血清TG、FFA较正常饮食组明显升高（P〈0．05）。高脂饮食组大鼠胰腺腺泡细胞出现空泡样改变及内质网扩张。体外培养6h后，高脂饮食组胰腺腺泡细胞活力低于对照组（P〈0．05），且各浓度CCK-8引起的淀粉酶和LDH释放均高于正常饮食组（P〈0．05）。结论饮食诱导的高三酰甘油血症可以引起大鼠胰腺腺泡细胞损伤。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.