阿托伐他汀与罗格列酮对缺血再灌注心肌的作用及可能机制

目的:探讨阿托伐他汀、罗格列酮及两药联合应用对大鼠急性缺血再灌注(I/R)心肌的作用及可能机制。方法:将健康雄性SD大鼠63只随机分5组:假手术组(7例)、I/R组(14例)、阿托伐他汀组(14例)、罗格列酮组(14例)、阿托伐他汀+罗格列酮组(14例)。灌胃1周后制作大鼠在体心肌I/R模型。再灌注后,测定血清心肌酶及一氧化氮(NO);心肌组织丙二醛(MDA)及总超氧化物歧化酶(TSOD);Evansblue、TTC双重染色后,用计算机图像分析软件计算梗死面积。结果:阿托伐他汀组、罗格列酮组、阿托伐他汀+罗格列酮组与I/R组比,心肌梗死面积减少,乳酸脱氢酶(LDH)、肌酸激酶(CK)降低,NO升高;TSOD升高、MDA降低(P0.01)。阿托伐他汀+罗格列酮组较阿托伐他汀组、罗格列酮组心肌梗死面积减少;LDH、CK降低,NO升高;TSOD升高、MDA降低(P0.01);较假手术组NO、TSOD降低,MDA升高(P0.01),LDH、CK升高(P0.05)。阿托伐他汀组与罗格列酮组各指标水平接近(P0.05)。结论:阿托伐他汀、罗格列酮及两药联合应用能明显减轻心肌I/R损伤;其作用机制与增加NO含量、提高心肌组织TSOD活性,降低MDA含量有关。     

洛伐他汀在大鼠心脏急性缺血再灌注中的延迟性心肌保护作用及其机制的研究

目的:探究洛伐他汀在大鼠心脏急性缺血再灌注中的延迟性心肌保护作用及其机制。方法:将24只Sprague-Dawley(SD)大鼠随机分为3组(n均=8):模型对照组(C);洛伐他汀(Lovastatin)组(L),胃管直接灌注洛伐他汀15mg·kg-1·d-12周;洛伐他汀复合L-硝基精氨酸甲酯(L-NAME)组(N),洛伐他汀15mg·kg-1·d-1直接灌胃2周同时腹腔注射L-NAME30mg·kg-1·d-1;2周后建立在体急性缺血再灌注心脏模型,监测缺血再灌注前后血流动力学各项指标,同时观察各组血脂水平及其血浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、乳酸脱氢酶(LDH)以及肌酸激酶(CK)的变化情况。结果:L组和N组较C组心率明显减慢(P<0·01),缺血再灌注心律失常消失和再灌注时左心室内压下降最大速率(-dp/dtmax)下降程度减轻(P<0·05);洛伐他汀明显减少再灌注时血浆中MDA生成和LDH及CK的释放(P<0·01),并且提高心肌组织SOD活性(P<0·05),各项血脂指标不变。结论:洛伐他汀对大鼠心脏急性缺血再灌注时具有延迟性心肌保护作用。这种保护作用除与其增加一氧化氮(NO)合成相关外,还可能通过直接或间接方式稳定心肌细胞膜表面的离子通道,减少再灌注心律失常的发生,具体机制需待进一步实验证明。     

辛伐他汀缺血后处理对大鼠心肌缺血再灌注损伤的保护作用

目的探讨辛伐他汀缺血后处理对大鼠心肌缺血再灌注（I/R）损伤的保护作用及机制。方法采用Langendorff离体心脏灌流模型,将32只大鼠随机分为四组各8只。对照组用改良K-H缓冲液持续灌流;I/R组用改良K-H缓冲液稳定灌注、停灌、再灌;治疗组用改良K-H缓冲液稳定灌注、停灌后,在K-H缓冲液中加入辛伐他汀20μmol/L再灌;K-H缓冲液再灌;N-硝基-L-精氨酸甲酯（L-NAME）组用改良K-H缓冲液稳定灌注、停灌后,在K-H缓冲液中加入辛伐他汀20μmol/L、L-NAME 100μmol/L再灌,K-H缓冲液再灌。观察各组再灌注心律失常发生情况,检测其冠脉流出液中的肌酸激酶（CK）、乳酸脱氢酶（LDH）、NO,心肌组织总超氧化物歧化酶（T-SOD）活性、丙二醛（MDA）及细胞凋亡指数（AI）。结果与I/R组比较,治疗组心律失常发生率下降,CK、LDH、MDA及细胞AI降低,T-SOD活性、NO升高（P均〈0.01）;与治疗组比较,L-NAME组心律失常发生率升高,CK、LDH、MDA及细胞AI升高,T-SOD活性、NO降低（P均〈0.01）。结论辛伐他汀缺血后处理能减轻大鼠心肌I/R损伤,其作用机制与清除氧自由基、增加NO含量、减少心肌细胞凋亡有关。     

L-硝基精氨酸甲酯对大鼠肢体缺血再灌注继发心肌损伤的影响

目的 研究L-硝基精氨酸甲酯(L-NAME)对肢体缺血再灌注(LIR)后心肌损伤的影响.方法 止血带法制作LIR大鼠模型,随机分成缺血再灌注组(A组)、L-NAME处理组(B组)、对照组.B组在再灌注前经静脉给予L-NAME 10 mg/kg,A组和对照组静注等量生理盐水.观察三组心肌组织丙二醛(MDA)、髓过氧化物酶(MPO)、肿瘤坏死因子-α(TNF-α)、血浆磷酸激酶(CK)、磷酸激酶同工酶(CK-MB)及NO含量;心脏插管检测平均动脉压(MAP)、左心室收缩压(LVSP)、收缩期左室内压上升最大速率(DP/Dtmax)、舒张期左室内压下降最大速率(-DP/Dtmax);光镜下观察心肌组织的形态学变化.结果 A、B组心肌组织MDA、MPO和TNF-α含量增加(P<0.01,<0.05),血浆CK、CK-MB及NO水平升高(P<0.01),MAP、LVSP等血流动力学指标下降,镜下可见心肌细胞水肿等组织损伤征象.静脉给予L-NAME后,心肌组织MDA、MPO含量增加和血浆CK、CK-MB及TNF-α升高更加明显(P<0.01或P<0.05),NO、DP/Dtmax、-DP/Dtmax显著下降(P<0.01),光镜下心肌组织的损伤性表现加重.结论 L-NAME可能通过抑制体内NO生成而加重大鼠LIR继发的心肌损伤.     

阿托伐他汀对缺血再灌注损伤下内皮祖细胞的保护作用

目的:探讨阿托伐他汀对缺血再灌注损伤下内皮祖细胞(EPCs)的保护作用及其机制。方法:分离SD大鼠骨髓中单个核细胞,采用差速贴壁法纯化,间接免疫荧光法鉴定EPCs。将EPCs随机分成对照组(C组)、缺血再灌注组(IR组)、阿托伐他汀组(A组)、缺血再灌注/阿托伐他汀组(IR/A组)及阿托伐他汀/缺血再灌注组(A/IR组)。采用MTT法测定EPCs增殖情况,并检测细胞培养液中乳酸脱氢酶(LDH)释放量及一氧化氮(NO)及总一氧化氮合酶(TNOS)分泌量。结果:与C组比较,IR组EPCs增殖减慢,NO和TNOS分泌量减少,LDH释放量明显增加。经阿托伐他汀预处理后,与IR组相比,EPCs增殖快,NO及TNOS分泌量升高,LDH释放量减少。结论:阿托伐他汀通过促进EPS增殖和NO分泌,对缺血再灌注损伤状态下的EPCs有保护作用。     

阿托伐他汀和辛伐他汀对心肌缺血再灌注电生理参数及室性心律失常的影响

目的探讨阿托伐他汀,辛伐他汀对急性心肌缺血再灌注电生理参数及室性心律失常的影响。方法 36只新西兰大白兔随机分成对照组、缺血再灌注组、阿托伐他汀组和辛伐他汀组,每组各9只。制备冠状动脉灌流的兔左室楔形心肌块的灌注模型,同步记录楔形心肌块心内膜、心外膜动作电位和容积心电图。观察缺血再灌组,阿托伐他汀组和辛伐他汀组急性缺血30 min和再灌注15 min时的QT间期和内、外膜动作电位复极达90%时程(APD90)以及跨室壁复极离散度(Tp-e/QT)的变化,同时以程序性刺激观察各组缺血和再灌注时室性心律失常的诱发率。结果缺血再灌注组缺血时与对照组比较,QT间期,内、外膜APD90均显著减少(P均﹤0.05);再灌后与缺血时比较,上述参数均增加,使得Tp-e/QT得到一定的恢复(P﹤0.01)。与缺血再灌注组相比较,阿托伐他汀组各项电参数没显著性改变(P均﹥0.05),而辛伐他汀组与阿托伐他汀组比较,各项参数亦无显著变化。对照组未诱发心律失常,其余三组在缺血时均诱发了心律失常,但各组比较无显著性(5/9 vs 6/9 vs 4/9),再灌注时,阿托伐他汀组和辛伐他汀组诱发心律失常的发生明显低于缺血再灌注组(0,1/9 vs 5/9,P﹤0.01)。结论阿托伐他汀和辛伐他汀能降低兔再灌注状态下室性心律失常的发生。     

阿托伐他汀对大鼠心肌缺血再灌注损伤保护作用的研究

目的:探讨阿托伐他汀预处理对大鼠心肌缺血再灌注损伤(MIRI)的保护作用。方法:将20周龄的Wistar大鼠175只随机分为三组:假手术组(n=55)、缺血再灌注组(n=60)、阿托伐他汀组(n=60)。在连续空腹灌胃7d后构建大鼠MIRI模型,测量比较三组大鼠血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、超敏C反应蛋白(hsCRP)水平的差异,再连续灌胃28d后测量比较三组大鼠左、右心室重量及室间隔厚度的差异。结果:与假手术组比较,缺血再灌注180min后缺血再灌注组、阿托伐他汀组LDH[(583.15±73.16)U/L比(1537.67±280.73)U/L比(1035.07±137.92)U/L]、CK[(932.72±62.82)U/L比(2872.45±136.3)U/L比(2434.07±192.81)U/L]、hsCRP[(20.98±1.86)mg/L比(48.39±1.31)mg/L比(40.29±2.33)mg/L]水平显著升高,但阿托伐他汀组的显著低于缺血再灌注组(P0.05或0.01)。与假手术组比较,缺血再灌注28d后缺血再灌注组、阿托伐他汀组左室相对重量[(1.21±0.17)mg/g比(1.94±0.33)mg/g比(1.53±0.35)mg/g]、右室相对重量[(0.16±0.12)mg/g比(0.39±1.21)mg/g比(0.27±0.07)mg/g]、室间隔厚度[(1.26±0.35)mm比(2.03±0.38)mm比(1.65±0.38)mm]显著增加,但阿托伐他汀组的显著低于缺血再灌注组(P均0.01)。结论:阿托伐他汀预处理能够显著减轻心肌缺血再灌注损伤,改善心室重构。     

L-Arg和L-NAME对大鼠脑缺血再灌注早期P-选择素及炎症损伤的影响

目的 研究一氧化氮(NO)底物L-精氨酸(L-Arg)和NO合酶抑制剂N-亚硝基-L-精氨酸甲酯(L-NAME )对大鼠脑缺血再灌注(I/R)早期P-选择素及炎症损伤的影响.方法 建立大鼠I/R模型,并设立假手术组.入选I/R模型大鼠随机分为3组,分别于缺血早期给予L-Arg、L-NAME和等体积生理盐水.测定缺血2 h再灌注8 h后脑组织NO、P-选择素含量、髓过氧化物酶(MPO)活性及脑梗死体积.结果 I/R加L-Arg组再灌注后NO含量明显高于I/R加盐水组(P<0.01),而P-选择素表达和MPO活性显著降低(P<0.01),同时脑梗死体积减小(P<0.05);而给予L-NAME后减少了脑NO含量(P<0.01),增加了P-选择素表达(P<0.05),导致脑缺血再灌注损伤的加重.结论 大鼠脑缺血早期使用L-Arg可以通过减低P-选择素的表达对脑缺血再灌注起到保护作用.     

洛伐他汀预适应在大鼠急性缺血再灌注中的心肌保护作用

目的:探讨洛伐他汀预适应对大鼠心脏急性缺血再灌注中的心肌保护作用及其机制。方法:将 24只SD大鼠随机分为3组(每组均8只):模型对照组(C组); 洛伐他汀组( L组),胃管直接灌注洛伐他汀 15 mg·kg-1·d-12周;洛伐他汀复合L 硝基精氨酸甲酯(L NAME)组(N组),洛伐他汀直接灌胃 2 周同时腹腔注射L NAME 30 mg·kg-1·d-1;2周后建立体内急性缺血再灌注心脏模型,监测缺血再灌注前后血流动力学各项指标,同时观察各组血脂水平及其血浆中丙二醛(MDA) 、心肌组织内超氧化物歧化酶(SOD)变化情况。结果: L组和N组较C组心率明显变慢(P<0.01),缺血再灌注心律失常消失和再灌注时-dp/dtmax下降明显改善(P<0.05);同时各项血脂指标不变,洛伐他汀能明显减少再灌注时血浆中MDA生成, 并且提高心肌组织SOD活性(P<0.05)。结论:洛伐他汀预适应对体内大鼠心脏急性缺血再灌注时具有非降脂外的心肌保护作用,其机制除与其增加一氧化氮(NO)合成相关外,可能还有其他物质或途径参与。     

一氧化氮对犬心肌顿抑心功能的影响

目的探讨心肌顿抑(myocardialstunning,MS)时局部组织一氧化氮(NO)含量的变化,及补充或抑制NO对顿抑心肌功能的影响.方法将35条犬随机分为5组(每组7条),即MS组、亚硝基左旋精氨酸甲酯(NG-nitro-L-argininemethylester,L-NAME)组、左旋精氨酸(L-Arginine,L-Arg)组、3-morpholinosydnonimine(Sir-1,一种NO供体)再灌注组及对照组.实验组均通过开胸阻断左冠状动脉前降支(LAD)15min再灌注3h建立MS模型,采用微电极法和Greiss法检测心肌表面及冠状窦血中NO含量变化,根据血流动力学监测及经食管彩色多普勒血流仪(transesophagealechocardiography,TEE)观察心功能及缺血节段室壁运动的变化.结果(1)阻断犬LAD15min后,所有犬均发生MS,主要表现为前壁室壁运动减弱,左室±dp/dt减低;(2)缺血再灌注期,顿抑心肌合成NO减少,L-Arg及Sin-1可明显增加顿抑组织的NO含量,而L-NAME则降低NO含量;(3)再灌注L-Arg及Sin-1在早期即可明显减轻顿抑心肌的室壁运动障碍,使心功能相对改善.结论心肌顿抑时局部顿抑组织NO含量减低,再灌注早期补充NO供体Sin-1及前体L-Arg可明显改善顿抑心肌的缩舒功能,而用L-NAME阻断NO的合成后则无此作用.     

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.     

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.     

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.