肾上腺髓质素和内皮素-1在大鼠肝肺综合征发病机制中的作用

[目的]探讨肝肺综合征(HPS)的发病机制.[方法]采用胆总管结扎(CBDL)术制备大鼠HPS模型,观察肺组织肾上腺髓质素(ADM)、内皮素-1(ET-1)及其受体(ETRA和ETRB)的表达和分布.[结果]在大鼠HPS形成过程中,血浆和肺组织中ADM、ET-1水平动态升高,且与肺泡-动脉氧分压差(A-aDO2)正相关;HPS大鼠肺组织中ADM、内皮素前体原(ppET-1 mRNA)的表达较假手术组明显增强,差异均有统计学意义(P＜0.05).HPS大鼠肺血管ETRA的分布及染色强度与假手术组比较无明显变化,而ETRB在远端肺小动脉和小静脉内膜上表达明显增强.图像分析结果显示CBDL 5周(w)组大鼠ETRA染色面积、平均积分光密度值与假手术组比较差异无统计学意义(P＞0.05),而CBDL 5 w组大鼠ETRB染色面积和平均积分光密度值明显高于假手术组,差异均有统计学意义(P＜0.05).[结论]扩血管物质ADM和缩血管物质ET-1的共同作用可能参与HPS的发生,肺组织中升高的ET-1可能更多地通过与在肺血管表达增强的ETRB结合从而扩张肺血管.     

血管活性物质在大鼠肝肺综合征发病机制中的作用

目的:探讨内皮素-1(endothelin-1,ET-1)、一氧化氮(nitric oxide,NO)、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在大鼠肝肺综合征(hepatopulmonary syndrome,HPS) 发病机制中的作用.方法:健康Wistar大鼠32只随机平均分为假手术组、CBDL术后3 wk组、4 wk组、5 wk组.采用胆总管结扎(common bile duct ligation, CBDL)术制备大鼠HPS模型成功后,行肝功能及肝肺病理检查.放射免疫分析法检测大鼠血浆和肝组织、肺组织匀浆中ET-1和CGRP的水平,利用硝酸还原酶法检测大鼠血清和肝、肺组织匀浆中NO的水平.结果:在大鼠HPS形成过程中,肝细胞变性、坏死,大量纤维组织增生,形成假小叶.肺泡毛细血管增生、扩张.伴肺泡间隔增宽、容量减小.术后3-5 wk,CBDL组大鼠血浆和肝、肺组织匀浆中ET-1、NO、CGRP水平显著升高,且与ALT水平呈正相关(血浆,ET-1:r=0.9889,P=0.0111:NO:r-=0.9935,P=0.0065;CGRP:r=0.9714.P=0.0286;肝组织:r=0.9969,P=0.0035;r=0.9993,P=0.0070;r=0.9507,P=0.0493;肺组织:r=0.9939,P=0.0061;r=0.9991,P=0.0009;r=0.9557,P=0.0443).结论:在大鼠HPS形成过程中,血浆和肝、肺组织匀浆中ET-1,NO和CGRP水平持续升高,提示血管活性物质ET-1,NO和CGRP在其发病机制中可能起着一定作用.     

肝肺综合征大鼠肺组织内皮素-1及其受体基因的表达

目的探讨内皮素-1及其受体在大鼠肝肺综合征(HPS)发病机制中的作用。方法分别采用RT-PCR和原位杂交方法检测HPS大鼠肺组织内皮素前体原(ppET-1)mRNA水平及两种亚型内皮素-1(ET-1)受体ETRA和ETRB在HPS大鼠肺组织的分布和表达。结果HPS大鼠肺组织ppET-1mRNA表达显著升高(0.48±0.06),为假手术(Sham)组表达量(0.21±0.04)的2.3倍(t=2.4114,P<0.05)。HPS大鼠肺血管ETRA的分布及染色强度与Sham组比较无明显变化,染色面积和平均积分光密度值与Sham组比较差异无统计学意义(P>0.05),而ETRB在远端肺小动脉和小静脉内膜上表达明显增强,尤以静脉明显。ETRB染色面积和平均积分光密度值明显高于Sham组(P<0.001)。结论HPS大鼠肺组织ET-1基因表达水平升高。ET-1在HPS大鼠肺血管的总体反应可能由于ETRB表达的增高而表现为扩张。     

肝肺综合征大鼠肾上腺髓质素及其受体的表达

目的 探讨肾上腺髓质素(ADM)在肝肺综合征(HPS)发病机制中的作用。方法 采用Wistar大鼠行胆总管结扎术(CBDL)制备HPS动物模型，进行血气分析，使用放射免疫方法检测血浆和肺组织匀浆中ADM水平；采用RT-PCR方法检测肺组织中ADM mRNA及其特异性受体Ll mRNA的表达。结果(1)从术后第3周至第5周，CBDL组大鼠血浆和肺组织中ADM水平动态升高；(2)CBDL 5周组大鼠肺组织中ADM mRNA的表达较对照组升高，差异有显著性(P＜0．05)，而两组间Ll mRNA的表达差异无显著性(P＞0．05)；(3)相关分析表明，各阶段血浆和肺组织ADM水平均与天冬氨酸转氨酶(AST)、门静脉压力、肺泡-动脉氧分压差(A-aDO2)呈正相关，出现腹水者血浆和肺组织ADM水平高于未出现腹水者。结论 在HPS形成过程中，血浆和肺组织中扩血管物质ADM水平持续升高，与肝功能受损状态、门脉压力升高程度、腹水形成及PaO2降低有关，提示ADM增多可能参与HPS时肺内血管扩张(IPVD)的发生。     

实验性肝肺综合征大鼠肺组织血红素氧合酶-1的表达

目的探讨血红素氧合酶-1(heme oxygenase-1,HO-1)在肝肺综合征(hepatopulmonary syndrome,HPS)大鼠肺组织中的动态表达。方法采用Sprague-Dawley大鼠胆总管结扎术(common bile duct ligation,CBDL)方法制备HPS动物模型,随机分为假手术组(sham operation,sham)、2周组和5周组,每组6只。采用HE及Masson染色观察肝硬化形成情况,采用HE染色观察肺血管扩张,血气分析检测动脉血氧分压。应用免疫组化方法及Western-blot观察HO-1蛋白在肺组织的表达和分布特点,采用RT-PCR方法检测肺组织中HO-1 mRNA的表达。结果通过CBDL成功复制了HPS模型。免疫组化光镜下显示5周组肺组织血管壁及内皮细胞HO-1表达增高,而2周组和sham组表达不明显;Western blot显示5周组HO-1蛋白相对表达(1.22±0.18)明显高于2周组(0.12±0.03,P=0.00)和sham组(0.07±0.02,P=0.00),而2周组与sham组无显著性差异(P=0.58);RT-PCR显示5周组HO-1mRNA相对表达(1.84±0.17)明显高于2周组(0.77±0.22,P=0.00)和sham组(0.12±0.05,P=0.00),2周组明显高于sham组(P=0.03)。结论 HO-1随HPS的形成表达增加可能是HPS的发病机制之一。     

消臌软坚丸对肝硬化大鼠血细胞因子及血管活性因子的影响

目的:研究消臌软坚丸对肝硬化大鼠模型血清肿瘤坏死因子(TNF)、白细胞介素1、6(IL-1、IL-6)、一氧化氮及其合酶(NO、NOS)及血浆内皮素1(ET-1)的调控作用.方法:采用四氯化碳为主的复合因素造模法复制肝硬化大鼠模型,分为正常组、模型组、消臌软坚丸低剂量组和高剂量组及阳性药对照组(复方鳖甲软肝片),5组均于造模结束后第2天连续灌服0.85%氯化钠液或药物28 d后断头取血,分别检测血清TNF、IL-1、IL-6、NO、NOS及ET-1含量.结果:①消臌软坚丸各治疗组TNF、IL-1、IL-6的含量均低于模型组(P＜0.01),高剂量组低于对照组(P＜0.05或＜0.01);低剂量组IL-1、TNF的含量低于对照组(P＜0.01),而IL-6的含量与对照组之间差异无统计学意义(P＞0.05);高、低剂量组之间差异未见统计学意义(P＞0.05).②消臌软坚丸各治疗组NO、NOS的含量均低于模型组(P＜0.01);高剂量组NO、NOS的含量均低于低剂量组和对照组(P＜0.01);低剂量组NOS的含量低于对照组(P＜0.01).③消臌软坚丸各治疗组均能明显降低血浆ET-1的含量(P＜0.01).高、低剂量组ET-1的含量均低于对照组(P＜0.01).高剂量组ET-1的含量低于低剂量组(P＜0.01).结论:①消臌软坚丸可显著下调肝硬化模型大鼠血清异常升高的TNF、IL-1、IL-6的水平;②消臌软坚丸可显著降低肝硬化大鼠血NO、NOS、ET的含量.从而减轻炎症损害,改善系统高动力循环状态,缓解门脉高压及肝微循环障碍,减缓或抑制腹水的发生发展.     

内皮素-1在大鼠肝肺综合征发病机制中的作用

目的 探讨内皮素-1(ET-1)在大鼠肝肺综合征(HPS)发病机制中的作用.方法 应用放免法检测HPS大鼠血浆和肝、肺组织匀浆中ET-1的水平.结果 ①HPS大鼠血浆和肝组织、肺组织匀浆中ET-1水平动态升高.②各阶段血浆和肝、肺组织匀浆中ET-1水平与谷丙转氨酶(ALT)、总胆红素(TBIL)呈正相关.结论 在HPS形成过程中,血浆和肝、肺组织匀浆中ET-1水平持续升高,与肝功能损害有关,提示ET-1可能参与HPS的发生.肺组织匀浆中升高的ET-1可能更多地通过与在肺血管表达增强的内皮素受体B(ETRB)结合从而扩张肺血管.     

雄激素对高盐饮食状态下雄性大鼠血管内皮功能的影响

目的 探讨不同水平雄激素对高盐饮食状态下雄性大鼠血管内皮功能的影响.方法 雄性Wistar大鼠32只随机分为4组,每组各8只:假手术组(Sham),去势组(Cas),去势后补充睾酮组(TC),去势后补充睾酮和氟他胺组(FTC).各组均以8％NaCl高盐颗粒饲料喂养,Sham组施以假手术,Cas、TC及FTC组均施以去势手术.TC及FTC组予以丙酸睾酮(TP) 2mg/(kg·2d)皮下注射,FTC组同时予以氟他胺1mg/(kg·d)灌胃,持续8周.尾动脉脉压法测定各组实验前、实验4周、实验8周后尾动脉血压,8周后酶联免疫吸附测定法(ELISA)测定血清中睾酮(T)、内皮素1(ET-1)的浓度,比色法测定血浆中一氧化氮(NO)水平.结果 (1)与Sham组血压相比,Cas组和FTC组明显下降[Cas组:(124.8±4.4) vs(135.9±3.7) mmHg,P＜0.01;FTC组:(127.7±3.0)vs(135.9±3.7) mmHg,P＜ 0.01];与基础血压相比,Sham组和TC组明显升高(P＜0.01);(2)与Sham组T浓度相比,Cas组的明显下降[(0.26±0.02) vs (3.15±0.54) μg/L,P＜ 0.01],而FTC组明显升高[(5.47±1.29) vs(3.15±0.54) μg/L,P＜0.01];(3)与Sham组血清ET-1浓度相比,Cas组和FTC组明显下降[Cas组:(0.77±0.23) vs(1.08±0.15)μg/L,P＜0.01;FTC组:(0.80±0.21) vs(1.08±0.15) μg/L,P＜0.05]; TC组差异无统计学意义(P＞0.05);(4)与Sham组NO浓度相比,Cas组和FTC组明显升高[Cas组:(42.37±15.74)vs(17.20±7.32) mmol/L,P＜0.01; FTC组:(33.44±8.50) vs(17.20±7.32) mmol/L,P＜0.01];TC组差异无统计学意义(P＞0.05).结论 高盐饮食下,雄激素水平的变化可能影响雄性大鼠血管内皮功能.     

化瘀通脉方对动脉粥样硬化模型兔一氧化氮、内皮素-1表达的影响

目的观察化瘀通脉方对动脉粥样硬化(AS)模型兔一氧化氮(NO)、内皮素(EP)-1表达的影响。方法取雄性健康新西兰大耳白兔40只,随机分为空白组、模型组、对照组、治疗组,每组10只。采用免疫损伤加高脂饲料喂养方法建立新西兰大耳兔AS模型。测定血清NO、血浆ET-1水平。结果实验8 w末,AS兔血清ET-1显著升高,而NO显著降低(P0.05,P0.01)。实验16 w末,治疗组血清ET-1水平较模型组显著降低,NO较模型组显著升高(P0.05,P0.01)。结论化瘀通脉方具有较好的抗AS作用,这可能与其能有效地调节NO/ET-1平衡有关。     

肝肺综合征大鼠血细胞因子和肺血管巨噬细胞观察

目的：观察肝肺综合征大鼠肺组织中肺血管巨噬细胞浸润情况和血浆内毒素水平。方法取 Wistar大鼠30只,随机分为假手术组和胆总管结扎肝纤维化模型组（CBDL 组）,于造模5 w 末处死动物,收集血清及肝肺组织;分别检测血气、内毒素（鲎试验）、一氧化氮（硝酸还原酶法）、肿瘤坏死因子-α（ELISA 法）,观察肝、肺组织病理学变化及肺组织肺血管内巨噬细胞的浸润情况。结果在 CBDL 组动物,5 w 时血气分析示 PaO2为（64.2±7.3） mmHg,显著低于假手术组[（97.7±4.5）mmHg,P〈0.05）];CBDL 组5 w 时血浆内毒素、一氧化氮和肿瘤坏死因子-α分别为（0.2297±0.0362）Eu/ml、（56.2±9.5）μmol/L 和（1.5±0.2）ng/ml,均明显高于假手术组[（0.0938±0.0309） Eu/ml、（32.9±4.3）μmol/L 和（1.5±0.2）ng/ml,P〈0.05）];病理学检查示5 w 时模型组大鼠肝组织可见纤维化表现,肺组织中肺毛细血管扩张、充血,有肺血管巨噬细胞存在。结论在胆总管结扎法诱导的大鼠肝硬化模型中,血清内毒素水平升高、肺血管巨噬细胞浸润和炎性细胞因子分泌增加,可能是肺血管扩张、低氧血症及肝肺综合征发生的重要机制。     

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.