二丁基二氯化物尾静脉注射建立大鼠慢性胰腺炎模型

目的 探讨经尾静脉注射二丁基二氯化物建立大鼠慢性胰腺炎模型的方法,为慢性胰腺炎纤维化机制研究提供一种合适的动物模型.方法 将SD大鼠随机分为实验组和对照组,每组再分为1,7,14,21,28,60 d 6个观察点,每个时间点各5只大鼠.实验组大鼠尾静脉注射二丁基二氯化物8 mg/kg体重,对照组注射相同剂量的乙醇和甘油溶剂.上述时间点分别处死大鼠,收集血液和胰腺标本.检测血清淀粉酶、脂肪酶、透明质酸浓度.观察胰腺形态,病理改变,胶原染色评价纤维化程度.结果 造模后1 d胰腺组织水肿,表现为急性中度间质性水肿性胰腺炎;7 d炎症加重,表现为腺泡肿胀,散在的腺泡细胞坏死;14 d广泛的炎症细胞浸润,伴轻度纤维化;21 ～ 28 d胶原沉积,纤维化加重,可见大量的纤维结缔组织;60 d,胰腺小叶结构破坏,腺泡消失,广泛间质纤维化.结论 尾静脉注射二丁基二氯化物是一种简便、有效的大鼠慢性胰腺炎模型制作方法,能为慢性胰腺炎纤维化的研究提供合适的动物模型.     

大鼠慢性胰腺炎离体组织块高分辨氢质子磁共振波谱分析

目的 对CP大鼠离体胰腺组织块进行高分辨磁共振波谱分析,探索其代谢变化特征.方法 SD大鼠30只,数字随机法分为实验组(20只)与对照组(10只).实验组经尾静脉注射二丁基二氯化物8 mg/kg体重,对照组注射等量溶剂.胰腺组织行病理检查及胶原纤维染色.运用高分辨魔角旋转磁共振波谱技术对离体大鼠CP组织样品代谢物进行分析.结果 造模60 d后,11只大鼠胰腺小叶结构破坏,腺泡消失,炎症细胞广泛浸润,纤维组织大量增生,广泛间质纤维化,呈典型CP表现.波谱分析显示CP组织的磷酸胆碱(PC)和甘油磷酸胆碱(GPC)、牛黄酸(Tan)及乳酸(Lac)峰强度增加;甜菜碱(Bet)、谷氨酸(Glu)、丙氨酸(Ala)、异亮氨酸(Ile)、亮氨酸(Leu)、缬氨酸(Val)峰降低;而乙酸(Ace)、胆碱(Cho)峰强度则无明显差异.结论 离体大鼠CP组织具有显著的代谢特征,为人CP波谱分析研究奠定了实验基础.     

三硝基苯磺酸(TNBS)诱导大鼠胰腺纤维化的病理学演变

目的观察三硝基苯磺酸(TNBS)胰管内注射诱导大鼠慢性胰腺炎胰腺纤维化过程中的病理演变规律,进一步从病理学角度揭示其发生机制.方法通过胰管内注射含2% TNBS的乙醇磷酸盐缓冲液诱导大鼠慢性胰腺炎模型,对照组仅注射等体积乙醇磷酸盐缓冲液,并于术后72 h、3周、4周、5周、6周、7周处死大鼠.应用光镜、电镜观察不同时间点胰腺组织的病理学变化.结果 2%TNBS胰管注射后早期主要以胰腺组织炎症、水肿,腺泡细胞坏死等改变为主;3周后则以纤维化为主,主要表现为胰腺星状细胞活化和成纤维细胞增生,腺泡萎缩及间质内大量纤维沉积.结论胰管内注射TNBS引起的慢性胰腺炎的病理改变是基于胰腺实质急性损伤而发生的胰腺组织再生与修复,最终形成胰腺纤维化.     

三硝基苯磺酸（TNBS）诱导大鼠胰腺纤维化的病理学演变

目的：观察三硝基苯磺酸(TNBS)胰管内注射诱导大鼠慢性胰腺炎胰腺纤维化过程中的病理演变规律，进一步从病理学角度揭示其发生机制。方法：通过胰管内注射含2%TNBS的乙醇磷酸盐缓冲液诱导大鼠慢性胰腺炎模型，对照组仅注射等体积乙醇磷酸盐缓冲液，并于术后72h、3周、4周、5周、6周、7周处死大鼠。应用光镜、电镜观察不同时间点胰腺组织的病理学变化。结果：2%TNBS胰管注射后早期主要以胰腺组织炎症、水肿，腺泡细胞坏死等改变为主；3周后则以纤维化为主，主要表现为胰腺星状细胞活化和成纤维细胞增生，腺泡萎缩及间质内大量纤维沉积。结论：胰管内注射TNBS引起的慢性胰腺炎的病理改变是基于胰腺实质急性损伤而发生的胰腺组织再生与修复，最终形成胰腺纤维化。     

过氧化物酶体增殖物激活受体-γ在大鼠慢性胰腺炎进程中的表达及意义

目的 探讨过氧化物酶体增殖物激活受体-γ(peroxisome proliferator-activated receptor-γ,PPAR-γ)在大鼠慢性胰腺炎(CP)进程中的表达及其意义.方法 经大鼠尾静脉一次性注射二丁基二氯基锡方法制备CP模型.按体重随机分为对照组及造模后1、3、5、7、14、42 d组.行胰腺常规病理检查,Sirius Red染色观察胶原含量,测定胰腺组织髓过氧化物酶(MPO)活性,免疫组化法测定α-SMA、PPAR-γ蛋白的表达.结果 造模7d内胰腺呈急性炎症改变,42 d时出现不同程度的腺泡坏死、萎缩,淋巴细胞、单核细胞浸润,小叶内或小叶周围纤维化形成,伴胰管改变,符合从急性胰腺炎(AP)向CP的进展过程.造模后1d,胰腺组织MPO活性、α-SMA蛋白表达即显著增加[(0.78±0.71) U/g比(0.15±0.05)U/g,6.67 ±3.14比0,P值均＜0.05],之后随造模时间延长未继续增加.造模后7d,胶原含量达峰值,为(45.42±15.99)％,较对照组的( 10.87±2.28)％显著增加(P＜0.05),胶原沉积从仅在血管壁进展到沉积在导管周围至小叶内和(或)小叶周围.对照组PPAR-γ仅在血管壁呈阳性表达,表达量为0.17±0.41,随造模时间延长表达渐增强,42d达峰值,为4.83±2.71.结论 在CP造模过程中PPAR-γ蛋白表达逐渐增强,并发挥有限的抗炎症和抗纤维化作用.     

CT扫描对慢性胰腺炎大鼠早期诊断的意义

目的:评价与分析计算机断层成像(computed tomography,CT)对慢性胰腺炎动物模型诊断的意义.方法:采用二丁基二氯化物(dibutyltin dichloride,DBTC)大鼠尾静脉注射慢性胰腺炎动物造模方法.注射后第7天、14天、28天,正常对照组取4只,慢性胰腺炎组取6只动物麻醉并进行腹部CT扫描(观察胰腺大小、形态、钙化、假性囊肿、胰胆管扩张、肾周筋膜增厚情况、胰周情况),处死大鼠取血,检测血淀粉酶、脂肪酶、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、血糖、总胆红素(total bilirubin,TBIL).病理学HE染色观察胰腺组织纤维化情况.结果:AST、TBIL在慢性胰腺炎各期均有明显升高(P0.05),ALT在慢性胰腺炎水肿期和晚期较同期正常对照组有明显升高(P0.05),慢性胰腺炎各期血淀粉酶(amylase,AMY)、LIPA、空腹血糖(fasting blood glucose,FBG)与同期正常对照组相比均无明显差异.AST、ALT、TBIL在慢性胰腺炎大鼠各期有差异,而AMY、LIPA、FBG在慢性胰腺炎大鼠各期测值无差异.HE染色组织形态学变化在注射后第7天、14天、28天均有变化;同期CT值也有相应改变.结论:CT扫描对早期诊断慢性胰腺炎有一定意义.     

蛙皮缩胆囊肽诱致大鼠胰腺纤维化的实验研究

慢性胰腺炎以胰腺纤维化为主要病理组织学特征。由于慢性胰腺炎症状隐匿，诊断方法滞后，长期以来临床研究进展甚微。建立可靠的胰纤维化动物模型，对于胰纤维化的发病机制、诊断和治疗研究都具有重要意义。本文采用蛙皮缩胆囊肽(caerulein)反复腹腔注射建立大鼠胰纤维化模型，观察不同时期大鼠胰腺的病理变化、VG胶原染色结果及αlⅠ型胶原mRNA的表达来评估造模效果及可靠性。     

慢性胰腺炎的中西医结合治疗

慢性胰腺炎是胰腺实质的慢性炎症，分慢性复发性胰腺炎和慢性无痛性胰腺炎两种类型。慢性复发性胰腺炎在慢性胰腺损害的基础上常反复发作，无痛性胰腺炎组织损害较少见。慢性胰腺炎也可有急性发作性、持续性左上腹剧痛，特征为反复发生的上腹疼痛伴有不同程度的胰腺外分泌和内分泌功能失调，引起胰腺不同程度的外、内分泌功能不足。病理改变特征：胰腺腺泡和胰腺管慢性进行性受损和纤维化、钙化、假性囊肿形成，腺泡和胰岛细胞减少和萎缩。每年发病率在4～5／10万，40岁以上的男性多与女性。     

TGF-β_1及其在胰腺纤维化中的作用

慢性胰腺炎(chronic pancreatitis,CP)典型的病理表现为胰腺实质纤维化、腺泡细胞萎缩、胰管狭窄或扩张、胰管结石以及炎症细胞浸润。胰腺纤维化的本质是以胶原为主的细胞外基质(extracellular matrix,ECM)合成增多,而降解相对减少,两者失去动态平衡,致使过多ECM沉积。目前认为,在胆道梗阻、酒精、代谢、遗传等因素作用下,造成胰腺实质     

Hedgehog通路蛋白在慢性胰腺炎大鼠中的表达

目的 检测慢性胰腺炎(CP)组织中hedgehog信号通路相关蛋白Ptch、Smo和Gli 1的表达,探讨其意义.方法 60只SD大鼠按数字表法随机分为CP组(50只)和对照组(10只).经尾静脉注射二丁基二氯基锡(DBTC)溶液8 mg·ml-1·kg-1方法制备CP模型；对照组尾静脉注射100％乙醇和甘油配制成的有机溶剂1 ml/kg体重.6周后处死动物,取胰腺组织常规病理检查,Sirius red染色测定胶原含量,免疫组化和RT-PCR法检测Ptch、Smo、Gli 1蛋白及mRNA的表达.结果 制模后6周34只大鼠发展为CP,制模成功率为73.9％( 34/46).CP大鼠胶原含量显著高于对照组,差异有统计学意义[(38.52 ±6.49)％比(7.37±2.28)％,P＜0.05]；Ptch、Smo、Gli 1蛋白阳性表达率分别为73.5％、64.7％和52.9％；Ptch、Smo、Gli1 mRNA表达量分别为2.38±0.42、3.85±1.03、4.63±1.49,均显著高于对照组的蛋白无表达及mRNA的表达(0.23±0.16、0.14±0.05、0.57±0.12·P值均＜0.05).结论 CP组大鼠胰腺组织Ptch、Smo、Glill均呈高表达,表明hedgehog信号通路参与胰腺慢性炎症反应和纤维化进程.     

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.