非诺贝特对高胆固醇喂养兔主动脉斑块面积和肿瘤坏死因子α的影响

目的利用高脂饮食诱发动脉粥样硬化模型,观察非诺贝特的抗动脉粥样硬化作用,并探讨其机制。方法10只新西兰大白兔给予高胆固醇饮食饲养8周后,随机分为两组:高胆固醇组继续饲以高胆固醇饲料4周;非诺贝特组在饲以高胆固醇饲料的基础上给予非诺贝特[30 mg/(kg.d)],共4周。另选择普通饮食12周兔(n=5)作为对照组。测定饲养前后血清肿瘤坏死因子α水平和饲养后的主动脉斑块面积。半定量逆转录聚合酶链反应测定脂肪组织肿瘤坏死因子αmRNA的表达。结果非诺贝特组和高胆固醇组血清总胆固醇、低密度脂蛋白胆固醇水平均明显高于对照组(P<0.001),但两组间差异无显著性。非诺贝特组与高胆固醇组相比主动脉斑块面积(52.81%±6.92%比76.30%±8.61%,P<0.01)、血管内膜厚度(28.45±5.68μm比76.18±11.25μm,P<0.05)、血清肿瘤坏死因子α水平(2.11±0.26 ng/L比3.86±0.33 ng/L,P<0.05)以及脂肪组织肿瘤坏死因子αmRNA表达量(0.31±0.05比0.56±0.07,P<0.05)均显著降低。结论非诺贝特具有一定的抗动脉粥样硬化作用,其降低高胆固醇喂养兔血清肿瘤坏死因子α水平可能是其作用机制之一。     

阿托伐他汀对高胆固醇血症兔主动脉环氧合酶2的影响

目的检测环氧合酶2在高胆固醇血症兔主动脉粥样硬化中的表达,探讨阿托伐他汀对环氧合酶2表达的影响及其意义。方法选取健康雄性新西兰兔24只,随机分为正常饮食组(n=8)和高胆固醇饮食组(n=16),喂养8周后,将后者随机分为高胆固醇血症组(n=8)和阿托伐他汀组[2.5 mg/(kg.d),n=8],继续喂养6周后,取各组兔主动脉,行动脉粥样硬化病变面积测定,采用逆转录聚合酶链反应检测主动脉环氧合酶2 mRNA的表达,酶联免疫吸附法测定血清白细胞介素6水平,免疫组织化学法测定主动脉粥样硬化斑块中环氧合酶2和基质金属蛋白酶9的表达。结果高胆固醇饮食兔经阿托伐他汀干预6周后,动脉粥样硬化斑块面积较高胆固醇血症组显著缩小(43.0%±12.5%比83.0%±11.6%,P<0.05)。高胆固醇饮食兔主动脉环氧合酶2 mRNA表达较正常饮食兔明显增强(1.03±0.09比0.09±0.01,P<0.05),阿托伐他汀干预后明显下降(0.57±0.10,P<0.05),且主动脉环氧合酶2 mRNA表达与斑块面积和血清白细胞介素6水平均呈正相关(r分别为0.803和0.795,P均<0.05)。高胆固醇血症组14周时主动脉粥样硬化斑块中环氧合酶2蛋白表达明显增强,而阿托伐他汀组显著性降低(62.4%±8.5%比34.3%±8.8%,P<0.05),且环氧合酶2蛋白表达与基质金属蛋白酶9的蛋白表达呈正相关(r=0.887,P<0.05)。结论环氧合酶2在动脉粥样硬化的发生和发展中可能起重要的促进作用,阿托伐他汀可能通过降低高胆固醇血症兔主动脉及其粥样斑块中环氧合酶2的表达,抑制基质金属蛋白酶9和白细胞介素6的分泌,从而发挥降脂以外的抗炎症作用。     

普罗布考对主动脉粥样斑块形成及血栓调节蛋白的影响

目的观察普罗布考对动脉粥样硬化斑块形成及可溶性血栓调节蛋白的影响。方法将新西兰大白兔给予高胆固醇饮食8周后随机分为淀粉组、普罗布考组(给予普罗布考每天500 mg/kg)和对照组。第14周末处死动物进行主动脉病理学检测,酶联免疫吸附法测定可溶性血栓调节蛋白浓度。结果高胆固醇饮食8周后,总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平较0周时明显升高,普罗布考干预6周后胆固醇水平显著小于淀粉组(P<0.05),较8周时明显降低(P<0.01)。高胆固醇饮食14周后淀粉组主动脉可见明显的斑块形成,普罗布考组斑块面积虽较对照组增厚,但显著小于淀粉组(51.54%±8.32%比84.81%±9.35%,P<0.01);淀粉组主动脉内膜较对照组显著增厚,普罗布考组主动脉内膜厚度虽较对照组厚,但显著小于淀粉组(0.58±0.17 mm比1.62±0.18 mm,P<0.01)。正常饮食兔的可溶性血栓调节蛋白水平很低(0.65±0.25μg/L),高胆固醇饮食后逐渐升高,与淀粉组比较普罗布考干预6周后可溶性血栓调节蛋白水平显著降低(4.31±1.45μg/L比9.82±1.55μg/L,P<0.01);血浆可溶性血栓调节蛋白水平与动脉粥样硬化斑块的面积呈正相关(r=0.72,P=0.008)。结论普罗布考延缓动脉粥样硬化斑块的形成作用可能与其降脂及降低可溶性血栓调节蛋白水平,保护内皮功能有关。     

构建高表达组织型纤溶酶原激活物基因质粒预防兔动脉粥样硬化血栓形成

目的探讨组织型纤溶酶原激活物基因质粒在预防动脉粥样硬化及血栓形成中的作用。方法新西兰纯种兔20只,分为基因治疗组和模型组,每组各10只,基因治疗组双侧髂动脉内膜剥脱术 转基因治疗 高胆固醇饮食喂养;模型组双侧髂动脉内膜剥脱术 高胆固醇饮食喂养。4周后处死动物,观察动脉内粥样硬化病变和血栓形成;在处死动物的同时抽血检测D-二聚体含量。结果成功建立了兔髂动脉粥样硬化模型并获得了组织型纤溶酶原激活物在血管周围肌肉组织中的有效表达。构建的组织型纤溶酶原激活物基因质粒可显著抑制兔动脉血管损伤后平滑肌细胞增殖细胞核抗原表达(13.55±8.43比27.78±12.35)和血小板源生长因子BmRNA表达(3.54±1.78比20.40±11.25),显著减少血管内膜厚度(32.75±21.50μm比165.70±71.21μm)和内膜面积(0.41±0.47mm2比2.01±1.15mm2),且显著抑制了局部血管粥样硬化病变发展并使病变血管内血栓形成明显减少。结论构建的组织型纤溶酶原激活物基因质粒可用于预防兔实验性动脉粥样硬化血栓形成。     

小鼠腹主动脉斑块模型建立的两种方法及超高场强磁共振成像的应用价值

目的 探讨建立腹主动脉粥样硬化斑块模型的方法及超高场强磁共振成像(MRI)在活体监测及量化小鼠腹主动脉粥样硬化斑块中的应用价值.方法 高脂饮食法小鼠腹主动脉粥样硬化斑块模型的建立及磁共振检测(高脂饮食组):选择3批10～12月龄apoE-/-小鼠13只、WT鼠3只高脂饮食喂养,分别于喂养前、喂养3个月、喂养6个月3个时期进行小鼠腹主动脉7.0 T磁共振活体扫描.血管紧张素Ⅱ(AngⅡ)灌注法小鼠腹主动脉粥样硬化斑块模型的建立及磁共振检测(AngⅡ灌注组):选用10只6月龄apoE-/-小鼠,分为AngⅡ1000 ng·kg-1·min-1组3只、AngⅡ500 ng·kg-1·min-1组3只(以上两组均在背部埋置AngⅡ缓释泵14 d)和对照组为4只(埋置生理盐水缓释泵),分别于灌注前后行磁共振扫描,选用FLASH T1WI黑血及MSME-T2WI-PDWI双回波序列.高脂饮食组依次在各时期扫描后分别处死3、5、5只小鼠,AngⅡ灌注组于装泵后14 d行磁共振扫描,然后处死本组小鼠,取处死小鼠的肾动脉段腹主动脉制作病理切片,进行苏木素-伊红(HE)染色、Masson胶原纤维(CME)染色.每只小鼠选5～7层肾动脉段腹主动脉病理图像及多对比MRI图像,分别测量外腔面积(VOA)、内腔面积(LA),计算管肇面积(VWA)并进行MRI与病理测量结果的相关性分析.结果 两种方法建立的小鼠模型,其腹主动脉MRI与病理切片均可见不稳定斑块形成.高脂饮食组随着高脂饮食时间的延长,斑块进展,VWA不断增加,3个时期VWA方差分析F=29.94(P<0.05),斑块信号于PDWI、T2WI逐渐增加,且不均匀.高脂饮食组MRI测量的斑块面积与病理测量的斑块面积有较高的-致性(高脂喂养前、喂养3和6个月3个时期r值分别为0.84、0.95、0.90).病理切片中斑块成分与磁共振显示信号一致,均表现为脂质成分增加,纤维成分减少.AngⅡ1000 ng·kg-1·min-1组AngⅡ灌注后斑块面积与灌注前比较差异有统计学意义(P=0.017),分别为(2.65±0.48)mm2和(1.21±0.21)mm2,部分小鼠可见夹层动脉瘤形成.AngⅡ500 ng·kg-1·min-1组灌注后斑块面积也比灌注前有所进展,面积分别为(1.01±0.17)mm2和(0.85±0.11)mm2,MRI测量的斑块面积与病理测量的斑块面积有较高的一致性(r值为0.93).结论 AngⅡ灌注显著加快动脉粥样硬化进展并促进腹主动脉夹层动脉瘤形成,长期高脂饮食亦可形成晚期斑块.超高场强MRI多种序列黑血技术的综合应用能显示小鼠腹主动脉粥样硬化斑块的进展,其检测分析斑块大小结果与病理表现基本一致,对斑块成分的判定亦有一定价值.     

瑞舒伐他汀对冠状动脉粥样硬化患者临床前期病变的影响

目的评价瑞舒伐他汀对冠状动脉粥样硬化临床前期病变的影响。方法 100例经双源螺旋CT检测出的冠状动脉粥样斑块患者,随机分成观察组(n=51)及对照组(n=49):观察组给予瑞舒伐他汀100mg/d口服,对照组未行他汀类药物治疗。24个月后复查斑块情况。同时随访患者的血脂水平、超敏C反应蛋白水平(hs-CRP)及颈动脉中膜厚度(CIMT)。结果 51例患者接受瑞舒伐他汀治疗后总胆固醇(TC)降低14.92%,低密度脂蛋白胆固醇(LDL-C)下降24.22%,总甘油三酯(TG)下降17.06%,差异均有统计学意义(P0.05)。高密度脂蛋白胆固醇(HDL-C)增加7.52%,但差异无统计学意义(P0.05)。观察组冠状动脉斑块平均缩小(2.80±1.83)%,CIMT平均减少(0.11±0.02)mm,hs-CRP减少(2.95±0.24)mg/L,49例对照组斑块平均增加(2.17±1.73)%,CIMT平均增加(0.21±0.03)mm,hs-CRP增加(1.28±0.15)mg/L,差异均有统计学意义(P0.05)。结论瑞舒伐他汀能够有效降低血脂及hs-CRP水平,减少CIMT厚度,逆转或稳定冠状动脉粥样斑块。     

血管内超声检验兔动脉粥样硬化斑块的研究

目的建立兔动脉粥样硬化模型,通过血管内超声（intravascularultrasound,IVUS）检查粥样硬化斑块．评价IVUS在粥样硬化斑块诊断的临床价值。方法选取20只健康的新西兰大白兔,按简单随机化方法分为两组,每组10只。一组单纯喂养高脂饲料;另一组除喂养高脂饲料外,4周时行腹主动脉内膜损伤术。12周后行IVUS检查,标记斑块远端、近端图像。观察病变处内中膜厚度．并通过病理检查评价IVUS效果。通过病理切片．生物病理图像分析系统处理,分别测量两组兔斑块厚度,并与IVUS结果相比较．同时比较不同方法观察到的斑块性质。结果高脂饲料加内膜损伤组（8只）12周时斑块厚度明显高于纯高脂组（8只）,差异有统计学意义[（521．286±124．732）μm vs.（240．029±73．528）μm,P〈0．05]。IVUS显示所有兔子（16只）的斑块厚度为（412．7±165．8）μm,病理为（360．2±98．1）μm,两者比较差异无统计学意义（P〉0．05）;对于斑块性质的判断,两者比较差异也无统计学意义（P〉0．05）。结论采用动脉内膜损伤加高脂饮食的方式来制作动脉粥样硬化斑块的模型是可行的、实用的。IVUS对血管斑块性质的界定及厚度的测量结果可靠。     

高血清同型半胱氨酸水平与脑梗死及颈动脉硬化的临床研究

目的 研究血清同型半胱氨酸(Hcy)水平与脑梗死发生及其与颈动脉硬化的关系.方法 根据颈动脉彩色超声多普勒检查,将100例脑梗死患者分为脑梗死伴颈动脉粥样硬化斑块组(A组 )和脑梗死无斑块组(B组),每组50例.另选50名健康体检者为对照组.采用荧光偏振免疫法测定Hcy,比较脑梗死伴颈动脉粥样硬化斑块组、脑梗死无斑块组及对照组Hcy水平变化,记录患者性别、年龄、高血压病、吸烟、血脂、糖尿病等,应用彩色超声多普勒检查患者颈动脉内膜中层厚度(IMT),比较脑梗死伴颈动脉粥样硬化斑块组和脑梗死无斑块组内膜中层厚度.结果 脑梗死伴颈动脉粥样硬化斑块组的血Hcy水平为(33.80±16.70)μmol/L,高于脑梗死无斑块组(17.39±6.60)μmol/L和对照组(10.74±14.58)μmol/L(P<0.01).脑梗死无斑块组与对照组Hcy水平相比有统计学意义(P<0.05);脑梗死伴颈动脉粥样硬化斑块组颈动脉内中膜厚度(IMT)为(0.77 mm±0.25 mm),较脑梗死无斑块组颈动脉IMT(0.58 mm±0.29 mm)明显增厚(P<0.01).结论 高Hcy血症与缺血性脑卒中的发生密切相关,与颈动脉粥样硬化及斑块形成有关.     

益气活血剂对兔胸主动脉粥样硬化形成的作用

目的探讨中药益气活血剂对高脂饮食兔动脉粥样硬化的预防及其作用机制。方法取纯种新西兰大白兔50只,随机分为4组:正常对照组、高脂模型组、益气活血预防组及益气活血治疗组,观察时间为2月。治疗前后检测血脂,治疗结束后分别取主动脉组织作脂质定量,测胸主动脉粥样硬化斑块面积和内膜、血管壁厚度等。结果①益气活血剂治疗可以降低高脂模型组血胆固醇、甘油三酯、低密度脂蛋白胆固醇,其中甘油三酯水平显著降低(P<0.01)。②益气活血剂治疗可减少高脂模型组动脉粥样硬化的形成,使内膜面积、厚度减少(P<0.05),但对管腔面积无明显影响(P>0.05)。③镜下观察发现,高脂模型组主动脉弓内膜充满泡沫细胞,壁上可见明显的粥样斑块;益气活血治疗组动脉壁脂质沉积相对较轻。结论益气活血剂具有降低血脂和抑制动脉粥样硬化形成的作用。     

辛伐他汀、阿司匹林治疗颈动脉粥样硬化斑块疗效观察

用辛伐他汀、阿司匹林并辅以低胆固醇饮食及适量运动的方法治疗颈动脉粥样硬化，服药前后记录颈动脉管腔直径以及颈内外动脉粥样硬化斑块的数量、大小、内中膜厚度。结果治疗1．5～4a后，患者颈动脉粥样硬化斑块体积缩小或消失，认为该方法是稳定和消退动脉粥样硬化斑块的有效方法。     

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.