辛伐他汀对心肌梗死大鼠心室重构的影响

目的采用超声心动图检测评价辛伐他汀对改善大鼠心肌梗死(MI)后心室重构的作用。方法34只大鼠分3组:(1)MI组:仅结扎左冠状动脉前降支(LAD);(2)治疗组:结扎LAD,并用辛伐他汀40 mg.kg-1.d-1进行灌胃;(3)假手术组:开胸,但不结扎LAD。超声心动图检查心脏结构和功能,逆转录-聚合酶链式反应(RT-PCR)测定梗死区和非梗死区肿瘤坏死因子(TNF)-αmRNA表达,免疫印迹法和免疫组织化学染色法测定TNF-α蛋白的产生。结果超声心动图显示,MI组与假手术组比较,左心室舒张末期内径(LVEDd)显著增大,分别为(7.5±0.4)mm和(4.5±0.3)mm,短轴缩短率〔FS,分别为(20.5±2.5)%和(51.6±3.1)%〕和射血分数〔EF,分别为(41.4±4.3)%和(85.2±3.7)%〕明显降低(均为P<0.05)。与MI组比较,辛伐他汀显著减轻左心室扩张,改善左心室功能(P<0.05)。MI组TNF-αmRNA表达和蛋白质的产生较假手术组增加(均为P<0.01),而治疗组TNF-αmRNA表达和蛋白质的产生比MI组明显下降(P<0.05)。TNF-αmRNA表达和蛋白质生成与心功能下降呈正相关,辛伐他汀减轻TNF-α基因表达,改善心功能。结论辛伐他汀改善大鼠MI后心室的不良重塑,其机制可能与降低非梗死区和梗死区心肌内TNF-α基因表达和蛋白质合成有关。     

重组人生长激素对心肌梗死大鼠心功能及心肌炎性因子表达的影响

目的 观察重组人生长激素(rhGH)对大鼠急性心肌梗死后心功能及心肌炎性因子表达的影响. 方法 结扎大鼠左冠状动脉前降支建立心肌梗死模型,将术后24 h存活的大鼠随机分为对照组和rhGH组,另设假手术组.rhGH组给予rhGH 2 mg.kg-1.d-1皮下注射,对照组和假手术组给予等体积的生理盐水皮下注射,4周后观察rhGH对大鼠心功能及心肌细胞肿瘤坏死因子-α(TNF-α)、白介素-1p(IL-1p)、白介素-6(IL-6)、白介素-10(IL-10)mRNA表达的影响. 结果 与假手术组比较,对照组心肌组织中促炎性细胞因子TNF-α、IL-1β、IL-β和IL-10 mRNA表达(假手术组分别为0.10±0.02、0.08±0.01、0.18±0.01和0.14±0.05;梗死区分别为0.77±0.15、0.93±0.17、1.10±0.14和0.73±0.11;非梗死区分别为0.88±0.14、0.95±0.17、1.18±0.11和0.83±0.16)明显升高.与对照组比较,rhGH组心肌组织中TNF-α、IL-1β、IL-6 mRNA表达(梗死区分别为0.35±0.10、0.36±0.10、0.43±0.11;非梗死区分别为0.51±0.10、0.42±0.11、0.51±0.12)明显下降,IL-10 mRNA表达(梗死区为1.18±0.18;非梗死区为1.21±0.22)升高,P＜0.05.心脏超声显示rhGH组左室功能明显改善. 结论 早期rhGH治疗改善了心肌梗死大鼠心肌炎性因子表达和心脏功能.rhGH有效改善心功能与其降低心肌细胞促炎细胞因子和升高抗炎因子的作用有关.     

Omapatrilat对大鼠心肌梗死后心肌炎性细胞及心室重构的影响

目的探讨血管肽酶抑制剂omapatrilat对大鼠心肌梗死(myocardial infarction,MI)后心肌炎性细胞及心室重构的影响。方法建立大鼠经典急性MI模型,将实验小鼠随机分组为假手术组、MI组和omapatrilat干预MI组。其中Omapatrilat干预MI组为术后24 h予omapatrilat 40 mg.kg~(-1)·d~(-1)给药MI大鼠,而假手术组和MI组给予纯净水处理。术后第4周时通过Masson氏染色法检测心肌胶原容积分数以及心肌血管周围胶原面积;TUNEL染色法检测大鼠非梗死区心肌细胞凋亡指数;Western blot法检测细胞因子肿瘤坏死因子-α(tumor necrosisfactor,TNF-α)、白细胞介素-10(interleukin-10,IL-10)的蛋白表达。结果与假手术组比较,MI组非梗死区心肌组织炎性细胞因子TNF-α蛋白表达明显增加,差异有统计学意义(P0.05);抗炎细胞因子IL-10蛋白表达量无明显变化,差异无统计学意义(P0.05);胶原沉积增加、心肌细胞凋亡数量明显增多,差异有统计学意义(P0.01)。与假手术组比较,omapatrilat干预MI组TNF-α蛋白表达减少、IL-10蛋白表达增加,差异有统计学意义(P0.05)。而在非梗死区,omapatrilat干预MI组的心肌细胞凋亡数量以及胶原沉积均较MI组明显降低,差异有统计学意义(P0.01)。结论 omapatrilat可显著改善大鼠急性MI后的心室重构,其发挥作用的机制很可能与减轻心肌炎症反应相关,同时还可能涉及非MI心肌间质胶原沉积的减少以及抗心肌细胞凋亡作用。     

银丹心脑通软胶囊对大鼠急性心肌梗死后心肌组织TGF-β1表达的影响

目的观察银丹心脑通软胶囊对大鼠急性心肌梗死(AMI)后心肌组织非梗死区转化生长因子β1(TGF-β1)表达的影响。方法用结扎左冠状动脉前降支方法制成大鼠AMI模型,造模成功后将大鼠随机分为5组,银丹大剂量组(12只),给予银丹心脑通软胶囊1.6g/(kg·d)灌胃,银丹小剂量组(12只),给予银丹心脑通软胶囊0.8g/(kg·d)灌胃,阳性药卡托普利(开博通)对照组(12只),开博通5mg/(kg.d)灌胃,假手术组(只穿线不结扎,10只)、梗死模型组(MI组,12只),假手术组与梗死模型组给予同等剂量生理盐水。在梗死后4周剪取心脏标本,用反转录-聚合酶链式反应(RT-PCR)检测非梗死区心肌TGF-β1 mRNA的表达,计算左心室重量及心脏重量指数,行HE染色观察心肌组织学改变。结果与假手术组比较,4周后MI组左心室重量及心脏重量指数显著升高,心肌组织非梗死区TGF-β1 mRNA表达水平亦明显升高(P<0.01);各给药组与MI组比较均可显著减低心室重量及心脏重量指数及TGF-β1 mRNA表达水平,银丹心脑通软胶囊的作用强度与剂量呈正相关。结论TGF-β1参与了心肌梗死后心室重构过程,银丹心脑通软胶囊能够减低梗死后左室重量及心脏重量指数及减少TGF-β1的表达,能够改善梗死后的心室重构。     

白藜芦醇对脑组织缺血再灌注大鼠肿瘤坏死因子-α、白介素-6、基质金属蛋白酶9及白介素-1β水平影响

目的探讨白藜芦醇(Res)对脑组织缺血再灌注损伤的影响,以及其对炎症因子表达水平的影响。方法选取健康成年SPF级SD大鼠30只,体重200～220 g,按随机数表法分为三组:假手术组(Sham组)、脑组织缺血再灌注组(MI/R组)、脑组织缺血再灌注+白藜芦醇组(MI/R+Res组)。采用改良线栓法建立大鼠大脑中动脉栓塞模型,建模前连续7 d予MI/R+Res组腹腔注射Res 30 mg/kg,余两组腹腔注射等剂量的0.9%氯化钠溶液。采用酶联免疫吸附法(ELISA)检测三组血清中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、基质金属蛋白酶9(MMP-9)及白介素-1β(IL-1β)的水平;提取缺血脑组织,通过逆转录-聚合酶链式反应(RT-PCR)测TNF-α、IL-6、MMP-9 mRNA的水平。结果与Sham组相比,MI/R组及MI/R+Res组大鼠血清炎症因子TNF-α、IL-6、MMP-9及IL-1β的水平明显增加(P 0.05);与MI/R组相比,MI/R+Res组TNF-α、IL-6、MMP-9及IL-1β的水平显著减少(P 0.05);与Sham组相比,MI/R组及MI/R+Res组缺血脑组织TNF-α、IL-6、MMP-9 mRNA的表达明显增加(P 0.05);与MI/R组相比,MI/R+Res组TNF-α、IL-6、MMP-9 mRNA的表达显著降低(P 0.05)。结论 Res可以降低脑组织缺血再灌注大鼠炎症因子的表达水平,减轻炎症反应。     

急性心肌梗死急诊介入治疗对炎性细胞因子影响的研究

目的观察急性心肌梗死(AMI)患者的梗死相关血管开通前后致炎细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和抗炎细胞因子白细胞介素-10(IL-10)的动态变化。方法采用酶联免疫吸附法测定8例健康人(健康对照组)和22例AMI患者急诊经皮冠状动脉介入治疗(急诊PCI组)术前即刻、术后12、24 h,血浆IL-1βI、L-6、IL-10的变化,比较致炎细胞因子IL-1βI、L-6和抗炎细胞因子IL-10的变化幅度。结果再灌注前急诊PCI组患者血浆IL-10略高于健康对照组,但无统计学差异(P>0.05),IL-1βI、L-6却显著高于健康对照组[(27.98±8.76)ng/Lvs(20.44±11.32)ng/L,P<0.05;(31.89±6.89)ng/Lvs(15.55±3.81)ng/L,P<0.05];再灌注后122、4 h急诊PCI组患者血浆IL-1βI、L-6及IL-10均较术前显著增高(P<0.01,P<0.01,P<0.05)。急诊PCI组患者再灌注治疗后12 h抗炎细胞因子IL-10的升高幅度显著低于致炎细胞因子IL-1βI、L-6的升幅(P<0.01)。结论心肌缺血再灌注后致炎细胞因子较抗炎细胞因子增高更显著。     

芪丹通脉片对心肌梗死后大鼠心肌纤维化重构的影响

目的:观察益气活血复方芪丹通脉片（qidan tongmai tablet,QDTMT）对大鼠心肌梗死(MI)后心功能及左心室非梗死区心肌纤维化的影响。方法: 以结扎SD大鼠左冠脉前降支法建立MI模型,随机分为假手术(Sham)组、MI组、MI+QDTMT小剂量(MI-QDTMTL)组和MI+QDTMT大剂量(MI-QDTMTH)组。术后24 h各组均用生理盐水配制成等体积药液灌胃4周,4周后以多普勒超声评价心脏功能;测定心室的质量/体质量(HW/BW);以MASSON染色检测非梗死区胶原的含量;用RT-PCR法检测非梗死区转化生长因子-β1（TGF-β1）、Ⅰ型胶原蛋白（Collagen type 1,Col1）及Ⅲ型胶原蛋白（Collagen type 3,Col3）mRNA的表达水平。采用大鼠羟脯氨酸（HYP）的ELASA试剂盒检测非梗死区中HYP的含量。结果: ①术后4周心功能:与MI组比较,MI-QDTMTL组和MI-QDTMTH组左室舒张末期内径(LVEDD)和HW/BW均降低,而射血分数(EF)升高（P<0.01或P<0.05）;②非梗死区心肌胶原蛋白的含量: MI-QDTMTL组胶原和MI-QDTMTH组胶原含量均低于MI组（P<0.01）;MI-QDTMTH组胶原的含量明显低于MI-QDTMTL组(P<0.01);③非梗死区TGF-β1、Col1、Col3mRNA的表达:与MI组比较,MI-QDTMTL组、MI-QDTMTH组的TGF-β1 Col1、Col3 mRNA均显著降低(P<0.01或P<0.05);MI-QDTMTH组TGF-β1、Col1、Col3 mRNA的表达显著低于MI-QDTMTL组(P<0.05);④非梗死区HYP的含量: MI-QDTMTL组与MI-QDTMTH组HYP的含量低于MI组(P<0.05,P<0.01); MI-QDTMTH组HYP的含量低于MI-QDTMTL组(P<0.05)。结论: QDTMT通过下调MI交界区TGF-β1、Col1、Col3 mRNA的表达及HYP产生,进而抑制MI后非梗死区反应性胶原的过度沉积,且高剂量组比低剂量组的疗效更好,为防治MI后非梗死区心肌纤维化重构,改善心脏功能提供了新的治疗思路。     

米诺环素对急性心肌梗死大鼠心肌基质金属蛋白酶-2及转化生长因子-β1表达的影响

目的探讨大鼠心肌梗死后心肌间质基质金属蛋白酶-2(MMP-2)及转化生长因子-β1(TGF-β1)的表达与心室重塑的关系及米诺环素的干预影响.方法结扎SD大鼠冠状动脉前降支建立急性心肌梗死模型,随机分成心肌梗死对照组和米诺环素(30mg·kg-1·d-1)治疗组,2组又随机分为1、2和4周亚组;另设假手术组.应用免疫组化方法测定胶原的表达.用逆转录-聚合酶链反应法及免疫组化方法检测MMP-2、TGF-β1mRNA和蛋白表达情况.结果与假手术组相比,心肌梗死对照组MMP-2、TGF-β1的mRNA表达在各亚组明显升高(均P＜0.05),各亚组MMP-2、TGF-β1蛋白表达也均增高(均P＜0.05),非梗死区Ⅰ/Ⅲ胶原比例在2周和4周随之升高(均P＜0.05).而米诺环素治疗组MMP-2mRNA和蛋白表达在1、2和4周亚组,TGF-β1 mRNA和蛋白表达在1、2周亚组,均较心肌梗死对照组显著降低(均P＜0.05),Ⅰ/Ⅲ胶原比例在2周和4周亚组也显著降低(均P＜0.05).结论大鼠心肌梗死后心肌间质内MMP-2、TGF-β1的表达增高,非梗死区Ⅰ/Ⅲ胶原比例上升,是心室重塑发生发展的重要机制.米诺环素可通过抑制MMP-2、TGF-β1的表达,逆转Ⅰ/Ⅲ胶原比例改善心肌梗死后心室重塑.     

抗细胞因子治疗--靶向心肌细胞?

急性心肌梗死(AMI)后心室重塑是一个进行性的病理过程,最终导致心力衰竭。炎症性细胞因子,包括肿瘤坏死因子α(TNFα)、白细胞介素(IL)1β和IL6在AMI后被激活〔1〕,并诱导心肌组织产生类似心力衰竭的病理变化,包括心肌细胞肥大、凋亡、细胞外基质变化以及收缩能力障碍〔2〕。Ono等〔1〕在AMI大鼠模型中发现,TNFα、IL1β和IL6mRNA在梗死区和非梗死区表达均显著升高,且非梗死区细胞因子水平与左心室舒张内径(LVEDd)及胶原沉积正相关,提示促炎性细胞因子加速心室重塑过程。靶向性抗细胞因子治疗曾被寄予厚望,但大规模临床试验的…     

白细胞介素-1β和肿瘤坏死因子α在脑梗塞发病中的作用

目的:探讨白细胞介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)在脑梗塞(CI)发病中的作用。方法:应用PCR方法对纤溶酶原激活物抑制剂-1(PAI-1)基因启动子区-675位4G/5G基因进行检测,应用放射免疫法测定IL-1β、TNF-α血浆水平,应用RT-PCR法检测其mRNA表达水平,应用发色底物法检测血浆PAI-1活性。结果:①CI患者表现为4G/4G型11例,4G/5G型30例,5G/5G型13例;②血浆PAI-1活性为(0.99±0.08)×10~3AU/L,明显高于正常对照组的(0.72±0.13)×10~3AU/L,差异有极显著性意义(P<0.01);③CI患者IL-1β血浆水平为(0.45±0.24)μg/L,TNF-α血浆水平为(1.52±0.31)μg/L,正常对照组分别为(0.22±0.11)μg/L和(0.61±0.22)μg/L(P<0.01);CI组IL-1βmRNA表达水平为0.42±0.27,TNF-α为0.82±0.65,明显高于正常对照组的0.29±0.23及0.26±0.23,经统计学处理差异有极显著性意义(均P<0.01)。结论:①IL-1β、TNF-α表达水平、血浆PAI-1活性在CI患者中明显增高,提示IL-1β、TNF-α、血浆PAI-1活性在CI发病中起重要作用。②未发现IL-1β、TNF-α与PAI-1基因启动子区4G/5G基因多态性、血浆PAI-1活性有相关性。     

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.