非酒精性脂肪性肝炎大鼠肠道分泌液sIgA的变化

目的探讨非酒精性脂肪性肝炎形成过程中小肠分泌液sIgA和血浆内毒素水平的变化。方法 32只SD大鼠随机均分为对照组和模型组,对照组用普通饲料喂养,模型组通过高脂饮食建立大鼠非酒精性脂肪性肝炎（non-alcoholic steatohepatitis,NASH）模型,并分别在8、12周末处死每组大鼠各8只,测定大鼠小肠分泌液中sIgA的水平和门静脉血浆中内毒素水平,测定小肠组织匀浆中SOD的活性和MDA的含量,并测定大鼠血清中TG、TC、ALT、AST,HE染色观察肝脏病理改变。结果 8、12周模型组较正常对照组大鼠血清TC、ALT、AST明显升高（P〈0.05）,肝脏病理分别表现为单纯性脂肪肝、脂肪性肝炎。8周末时模型组大鼠门静脉血浆中内毒素、小肠分泌液中sIgA的水平与对照组相比无明显变化（P〉0.05）;12周末大鼠NASH阶段与对照组相比小肠分泌液中sIgA的水平明显降低（P〈0.05）,门静脉血浆中内毒素水平与对照组相比明显升高（P〈0.05）。并且门静脉血浆内毒素水平与小肠分泌液中sIgA水平呈负相关（r=-0.873,P〈0.05）。8、12周末时模型组大鼠小肠组织匀浆中SOD活性明显降低,MDA含量明显升高（P〈0.05）。结论非酒精性脂肪性肝炎形成过程中小肠分泌液中sIgA明显降低,说明肠道免疫屏障受损,并且可能与肠道脂质过氧化增强有关,可能是NASH发生发展的重要发病机制之一。     

甘氨酸对非酒精性脂肪性肝炎肠组织巨噬细胞移动抑制因子表达的影响

目的:研究探讨甘氨酸对非酒精性脂肪性肝炎大鼠肠组织巨噬细胞移动抑制因子(MIF)表达的影响。方法:将36只雄性SD大鼠,常规饲养1周后,随机分为3组:正常对照组大鼠(采用普通饲料喂养+生理盐水腹腔注射);模型组大鼠(采用高脂饮食+腹腔注射氧四环素);治疗组大鼠(采用高脂饮食+腹腔注射氧四环素+5%甘氨酸),造模4周、8周后分批处死。取肝脏标本做HE染色、观察肝脏形态学变化;检测血浆肿瘤坏死因子-α(TNF-α)、转氨酶(ALT、AST)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和门静脉血浆内毒素(ET)水平;取肠组织做HE染色,并用免疫组化的方法检测肠组织中MIF表达水平。结果:4周、8周时模型组大鼠门静脉ET水平、血浆TNF-α、AST、ALT、IL-6、IL-10均与对照组大鼠比较,差异有显著性意义(P0.05),治疗组大鼠与同期模型组相比较差异有显著性意义(P0.05);4周、8周时模型组大鼠肠组织MIF的表达水平较同期对照组大鼠有明显增多(P0.05),治疗组大鼠肠组织MIF的表达水平与同期模型组相比较,差异有显著性意义(P0.05)。结论:①采用高脂饮食结合氧四环素腹腔注射制备的大鼠非酒精性脂肪性肝炎(NASH)模型伴有肠源性内毒素血症(IETM)的形成。②在NASH发生发展过程中肠组织MIF表达逐渐增高,可能与肠免疫屏障受损有关;③甘氨酸可拮抗内毒素,下调肠组织MIF的表达水平。     

非酒精性脂肪性肝炎大鼠小肠黏膜结构变化的研究

目的:探讨非酒精性脂肪性肝炎形成阶段肠黏膜屏障的损伤情况.方法:24只雄性Wistar大鼠随机分为对照组(普通饮食)和模型组(高脂饮食),各组12只.8周、12周处死大鼠后称量体重、肝重,并计算肝指数,检测血清甘油三酯(TG)、丙氨酸氨基转移酶(ALT)、肿瘤坏死因子(TNF-α)水平及门静脉、腹主动脉血中内毒素(ET)水平;取小肠组织经透射电镜观察其超微结构的改变;取肝标本做HE染色,观察其病理变化.结果:8周、12周模型组大鼠肝指数与同期对照组相比差异有显著性意义(P＜0.01);8周模型组大鼠TG、ALT与同期对照组比较呈升高趋势,12周差异有统计学意义(P＜0.05);8周、12周模型组大鼠血清TNF-α水平与同期对照组比较明显升高(P＜0.05);8周、12周模型组大鼠门静脉ET水平较对照组明显上升(P＜0.05);腹主动脉血ET与同期门静脉ET比较,差异有显著性意义(P＜0.05);8周、12周观察模型组大鼠小肠组织病理学变化,发现肠上皮细胞变性、坏死、脱落,并有炎细胞浸润;透射电镜显示肠上皮连接增宽,绒毛稀疏、缺如,固有层水肿.结论:非酒精性脂肪性肝炎发生时伴有肠源性内毒素血症(IETM)的形成,IETM可促使炎症因子TNF-α释放增加,加重肝脏损害,IETM的形成与肠黏膜屏障受损有关.     

氧四环素腹腔注射制备大鼠非酒精性脂肪肝模型的实验研究

寻找一种经济、高效的制备大鼠非酒精性脂肪肝动物模型的方法。采用高脂饮食与腹腔注射氧四环素相结合的方案。在模型组于造模开始后的第2、4、8周末及对照组在第8周末,分别检测大鼠血清ALT、AST、TG、TC、丙二醛（MDA）、超氧化物岐化酶（SOD）,肝脏TC．、TC、MDA、SOD水平及肝组织学改变。2周末、4周末和8周末模型组血清中的ALT、AST、TG、TC和MDA升高,SOD降低;肝脏组织中的TG、TC和MDA升高,SOD减低;与对照组相比均有统计学意义;肝组织病理学检查显示第2周末和第4周末表现为脂肪肝性肝炎病变为主,8周末可出现轻度肝纤维化。采用高脂饮食结合腹腔注射氧四环素的方法是一种制备非酒精性脂肪肝模型理想方法之一。     

葛花醒酒养胃颗粒对酒精性肝病内毒素损伤的防治作用

目的探讨葛花醒酒养胃颗粒对酒精性肝病(ALD)内毒素损伤的防治作用.方法Wistar大鼠48只随机分为正常组、模型组、葛花醒酒养胃颗粒治疗组(简称治疗组)和肝泰乐对照组(简称对照组).实验采用梯度酒精定量灌胃法制备酒精性肝病大鼠模型,造模同时治疗组予葛花醒酒养胃颗粒汤150mg·kg-1·d-1,分2次灌胃,对照组予肝泰乐水38mg·kg-1·d-1,分2次灌胃,正常组予同容积生理盐水,每日灌胃2次,连续灌胃8周后采血,检测大鼠血浆内毒素(LPS)、血清酶(ALT、AST、GGT)、血脂(Tch、TG)及血清肿瘤坏死因子(TNF-α)的含量,同时用RT-PCR法测定肝组织中脂多糖结合蛋白(LBP)和脂多糖受体CD14mRNA的表达.结果模型组大鼠血浆内毒素和血清TNF-α水平明显高于对照组(P＜0.05),肝组织中LBP和CD14mRNA的表达明显高于对照组(P＜0.05);同时血清ALT、AST、GGT、TG明显升高(P＜0.05);治疗组血浆内毒素和血清TNF-α水平明显低于模型组(P＜0.05),LBP和CD14mRNA的表达明显低于对照组(P＜0.05),血清ALT、AST、GGT、TG水平明显降低(P＜0.05).结论葛花醒酒养胃颗粒对大鼠酒精性肝损伤有较好的防治作用.     

酒精性肝损伤大鼠肠道屏障功能改变及谷氨酰胺的保护作用观膊

目的 观察酒精性肝损伤大鼠肠道屏障功能的改变,并探讨谷氨酰胺的保护作用.方法 36只SD大鼠随机分为正常对照组(A组)、模型组(B组)和谷氨酰胺治疗组(C组),分别检测肠道细菌易位率、肠粘膜通透性,同时观察血生化、肝脏和末段回肠粘膜病理学改变.结果 与A组比,B组大鼠血清AST和ALT水平显著升高(AST:256.6±50.8 U/L对175.2±16.2 U/L,P＜0.05;ALT:86.5±5.4 U/L对53.7±13.2U/L,P＜0.05),C组无显著变化(P＞0.05);B组肠道细菌易位率明显增高(62.5%,P＜0.05),C组无显著变化(35.0%,P＞0.05);B组肠粘膜通透性显著升高(235.1±26.4 ml·min-1·cm2对30.1±33.6ml·min-1·cm2,P＜0.05),C组肠粘膜通透性比B组明显下降(190.9±19.8 ml·min-1·cm2对235.1±26.4 ml·min-1·cm2,P＜0.05);B组大鼠末段回肠病理损伤明显加重(3.8±0.9对0.4±0.5,P＜0.05),C组比B组明显下降(2.7±0.7对3.8±0.9,P＜0.05) .结论 大鼠酒精性肝损伤伴有肠道屏障功能改变,谷氨酰胺对大鼠酒精性肝损伤及肠道屏障功能具有双重保护作用.     

降脂复肝汤对高脂性脂肪肝模型大鼠肝脏保护作用及TNF-α表达的影响

目的 观察降脂复肝汤对高脂饮食诱导的非酒精性脂肪肝大鼠肝组织病理学、肝功能、血脂及肿瘤坏死因子α(TNF-α)的影响.方法 建立大鼠非酒精性脂肪肝模型.造模结束后,将造模组随机分为模型组、血脂康组和降脂复肝汤组,治疗12 w后,通过HE染色、血清生化以及免疫组化检测,观察降脂复肝汤对肝组织病理学、血清酶学、血脂以及TNF-α的影响.结果 血脂康组和降脂复肝汤组体重、肝重、肝指数、血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)及总胆固醇(TC)、甘油三酯(TG)低密度脂蛋白(LDL)均较模型组显著降低(P＜0.01,P＜0.05).免疫组化法结果显示,降脂复肝汤组TNF-α的表达较模型组明显降低(P＜0.01),而且,降脂复肝汤组比血脂康组作用明显(P＜0.05).结论 降脂复肝汤能明显改善高脂饮食诱导的脂肪肝大鼠肝脏的病理变化、减轻肝组织脂肪变性,同时,也能降低脂肪肝变性肝组织TNF-α的表达,这可能是其治疗高脂饮食诱导的非酒精性脂肪肝的作用机制之一.     

甘氨酸对NASH大鼠肝组织环氧合酶-2表达的影响

目的 探讨环氧合酶-2在非酒精性脂肪性肝炎发病机制中的作用以及甘氨酸对其表达的影响。方法 选择雄性Wistar大鼠54只,随机分为对照组、高脂饮食组和甘氨酸干预组,比较实验第8、12和16周末动物血浆ALT和内毒素水平及肝组织COX-2的表达情况。结果 在实验第12周和16周末,脂肪肝组动物血浆ALT较对照组明显增高（P〈0．05）,各期脂肪肝组和甘氨酸组动物腹主动脉血内毒素水平与对照组比较均无差异,而门静脉血内毒素水平明显上升,腹主动脉血与相对应的门静脉血内毒素比较有显著性差异（P〈0．01）;在第16周脂肪肝组和甘氨酸组COX-2表达呈阳性,甘氨酸处理组积分光密度值比脂肪肝组明显降低（P〈0．05）;在对照组、实验第8周和12周脂肪肝组肝内无COX-2 mRNA表达,但在第16周脂肪肝组动物肝内COX-2的相对表达量为0．67±0．04,甘氨酸组为0．43±0．04,两者比较有显著性差异（P〈0．05）;血浆内毒素水平与COX-2表达呈正相关（r=0．58,P〈0．01）。结论肠源性内毒素血症上调肝组织COX-2表达,后者在NASH发病机制中起着重要的作用,甘氨酸能降低内毒素水平,并使NASH大鼠肝内COX-2表达减少。     

超微脂康饮对非酒精性脂肪性肝病大鼠模型的疗效

目的观察超微脂康饮对实验性非酒精性脂肪肝(NAFLD)大鼠模型的疗效。方法 SD大鼠高脂饮食饲养6周后诱导非酒精性脂肪肝大鼠模型,肝脏病理切片证实造模成功;造模大鼠50只随机分为5组,超微脂康饮(低、中、高剂量)组给予相应剂量的超微脂康饮灌胃,壳脂胶囊组给予壳脂胶囊混悬液,模型组及空白组灌服蒸馏水,除空白组外,其余组仍予高脂饮食。6周后分别检测各组的肝功能、血脂、肝脂及肝脏组织学改变。各组之间比较采用单因素方差分析。结果超微脂康饮各组血清ALT、AST、肝组织脂质(TC、TG)等方面均优于模型组,差异均有统计学意义(P值均0.05),超微脂康饮中,低剂量组血清TG、TC显著优于模型组,差异均有统计学意义(P值均0.05);超微脂康饮各组血清ALT、AST、肝组织TC与壳脂胶囊组比差差异无统计学意义(P值均0.05)。模型组及超微脂康饮各组均存在不同程度的肝脏炎症活动度,但与模型组比较,超微脂康饮各组、壳脂胶囊组大鼠的肝脏炎症活动度均有不同程度的改善(P值均0.05),而壳脂胶囊组较超微脂康饮各组改善稍明显(P值均0.05)。结论超微脂康饮能改善NAFLD大鼠肝功能、降低血脂、抑制肝脏炎症,整体疗效与壳脂胶囊相当,对非酒精性脂肪肝具有一定疗效。     

酒精性脂肪肝大鼠肝组织骨桥蛋白表达的变化

目的探讨乙醇联合高脂饮食诱导脂肪肝大鼠肝组织骨桥蛋白（OPN）表达的变化。方法采用高脂饮食联合乙醇灌胃制备大鼠脂肪肝模型。在第6周末分别取血和肝组织,常规检测血生化指标和采用Westernblot法检测大鼠肝组织骨桥蛋白表达的改变。结果乙醇联合高脂饮食条件下大鼠血清ALT、AST、TG、TC水平升高（P〈0．05）,HDL-C降低（P〈0．05）;油红O染色结果显示乙醇联合高脂饮食组大鼠肝脏脂肪变明显;模型组大鼠肝组织OPN蛋白表达明显增强（P〈0．05）。结论骨桥蛋白表达增强在大鼠乙醇性脂肪肝的发病过程中起一定的作用。     

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.     

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.     

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.     

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.