抑郁对急性心肌梗死大鼠心肌细胞凋亡的影响

目的探讨抑郁对急性心肌梗死后大鼠心肌细胞凋亡的影响。方法 30只SD大鼠随机分为三组,假手术组,心肌梗死对照组,心肌梗死抑郁组,每组10只。制备相应模型并干预后,用TUNEL法检测心肌细胞凋亡,用免疫组织化学法检测心肌细胞Bcl-2、Bax蛋白的表达。结果心肌梗死抑郁组和心肌梗死对照组大鼠心肌细胞凋亡率以及心肌细胞Bcl-2、Bax蛋白表达均高于假手术组,差异有统计学意义(P<0.01),心肌梗死抑郁组大鼠心肌细胞凋亡指数以及心肌细胞Bax蛋白表达高于心肌梗死对照组,而心肌细胞Bcl-2蛋白表达低于心肌梗死对照组,差异有统计学意义(P<0.01)。结论抑郁可增加急性心肌梗死大鼠心肌细胞凋亡,其机制可能与促进促凋亡基因Bax表达、抑制抗凋亡基因Bcl-2表达有关。     

RNA干扰Bax对急性心肌梗死大鼠心肌细胞的保护作用

目的探讨RNA干扰Bax对急性心肌梗死大鼠心肌细胞的保护作用。方法采将45只大鼠随机分为假手术组、心梗组和Bax干扰组,采用结扎左冠状动脉前降支建立急性梗死大鼠模型,术后假手术组和心梗组心肌内注射脂质体,Bax干扰组心肌注射脂质体与Bax siRNA的混合物。治疗后72h处死大鼠,取心肌组织,采用荧光定量PCR和免疫组化分析心肌组织中Bax mRNA和蛋白质水平,采用2,3,5-三苯基氯化四氮唑染色法测定心肌梗死范围,并用TUNEL染色法分析心肌细胞凋亡指数。结果与假手术组比较,心梗组大鼠Bax mRNA和蛋白质明显增加(P0.05)。与心梗组比较,Bax干扰组大鼠Bax mRNA和蛋白质水平明显下降(P0.05)。与假手术组比较,心梗组和Bax干扰组心肌梗死范围明显增加(P0.05)。与心梗组比较,Bax干扰组大鼠心肌梗死范围明显下降(P0.05)。与假手术组比较,心梗组和Bax干扰组大鼠心肌细胞的凋亡指数明显增加(P0.05)。与心梗组比较,Bax干扰组大鼠心肌细胞凋亡指数明显下降(P0.05)。结论 Bax基因在大鼠心肌梗死模型心肌组织中的沉默可明显降低心肌梗死范围,降低心肌细胞的凋亡,对心肌具有很好的保护作用。     

原花青素对缺血再灌注大鼠心肌细胞凋亡及凋亡相关基因蛋白表达的影响

目的:观察原花青素对缺血再灌注大鼠心肌细胞凋亡相关基因半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、B型白细胞/2型淋巴细胞样蛋白(Bcl-2)和凋亡相关基因Bcl-2相关X蛋白(Bax)蛋白表达的影响,探讨原花青素在大鼠缺血再灌注心肌细胞凋亡中发挥的作用及可能的调控机制。方法:40只雄性SD大鼠随机等分为4组,即正常组,模型组,原花青素低剂量组[原花青素50 mg/(kg·d)],原花青素高剂量组[原花青素100 mg/(kg·d)],灌胃给药,每天1次,连续2周。末次给药后结扎冠状动脉左前降支(LAD)30 min再灌注120 min,建立大鼠心肌缺血再灌注模型。测定肌酸激酶同工酶(CK-MB)活性、心肌梗死面积;用Western blot检测各组细胞凋亡相关基因Caspase-3、Bcl-2、Bax蛋白表达;原位末端转移酶标记(TUNEL)法检测心肌细胞凋亡。结果:与正常组比较,模型组大鼠CK-MB活性显著增强、心肌梗死面积增大,心肌细胞凋亡指数升高,Caspase-3、Bax蛋白表达增强,Bcl-2蛋白表达、Bcl-2/Bax降低(P0.05);与模型组比较,原花青素高、低剂量组大鼠CK-MB活性显著减弱、心肌梗死面积减小,细胞凋亡指数显著降低,Caspase-3、Bax蛋白表达显著减弱,Bcl-2蛋白表达、Bcl-2/Bax增加(P0.05)。结论:原花青素可拮抗缺血再灌注大鼠心肌细胞凋亡,其机制可能与Caspase-3、Bax蛋白表达降低,Bcl-2表达升高,Bcl-2/Bax比例增加有关。     

有氧运动对衰老模型大鼠心肌细胞凋亡及Bcl-2和Bax蛋白表达的影响

目的 探讨有氧运动对衰老模型大鼠心肌细胞凋亡及Bcl-2和Bax蛋白表达的影响.方法 建立衰老大鼠模型,随机分为对照组和两组运动组,运动组分别给予6次/w、 3次(隔日)/w游泳训练,每次持续90 min,训练12 w,于末次训练48 h后处死动物,TUNEL法检测心肌细胞凋亡,免疫印迹法检测心肌Bcl-2、Bax的表达,并计算Bax/Bcl-2的比值.结果 与对照组相比,两组运动组心肌细胞凋亡指数(AI)均显著降低(P＜0.01),Bcl-2蛋白表达显著升高(P＜0.01),Bax蛋白表达降低(P＜0.05),Bcl-2/Bax显著升高(P＜0.01);与6次/w运动组相比较,3次/w运动组心肌AI降低(P＜0.05),Bcl-2升高(P＜0.05),Bax降低(P＜0.05),Bcl-2/Bax升高(P＜0.05).结论 长期有氧运动使 Bcl-2/Bax比值优化,降低心肌细胞AI,促进心肌细胞存活,延缓心肌衰老;隔日有氧运动效果更佳.     

高压氧预处理对正常和糖尿病大鼠缺血再灌注心肌细胞凋亡的影响

目的 探讨高压氧预处理对正常和糖尿病大鼠缺血再灌注心肌细胞凋亡及Bcl-2和Bax蛋白的影响.方法 雄性Wistar大鼠75只,随机分为正常大鼠对照组,正常大鼠缺血-再灌注组,正常大鼠高压氧预处理组,糖尿病大鼠对照组,糖尿病大鼠缺血-再灌注组,糖尿病大鼠高压氧预处理组,检测各组心肌凋亡及心肌Bax、Bcl-2蛋白表达.结果 ①正常大鼠高压氧预处理组凋亡指数与正常大鼠缺血-再灌注组相比[(33.15±4.36)％vs(41.72±3.47)％],糖尿病大鼠高压氧预处理组凋亡指数与糖尿病大鼠缺血-再灌注组相比[(41.69±5.79)％vs( 52.73±6.71)％]均明显降低,有统计学差异(P＜0.05).②正常大鼠高压氧预处理组Bax蛋白灰度值与正常大鼠缺血-再灌注组相比[(170.17±7.35)vs(157.50±8.12)],糖尿病大鼠高压氧预处理组Bax蛋白灰度值与糖尿病大鼠缺血-再灌注组相比[(141.17±6.77) vs (134.0±4.73)]均明显降低,有统计学差异(P＜0.05).③正常大鼠高压氧预处理组Bcl-2蛋白灰度值与正常大鼠缺血-再灌注组相比[(158.67±7.69) vs (171.83±8.66)],糖尿病大鼠高压氧预处理组Bcl-2蛋白灰度值与正常大鼠缺血-再灌注组相比[(166.0±10.53)vs(183.33±9.15)]相比均明显增高,有统计学意义(P＜0.05).结论 高压氧预处理对正常及糖尿病大鼠均有抗心肌细胞凋亡的作用,但对正常大鼠保护作用更强,其保护机制可能与下调Bax蛋白表达,上调Bcl-2蛋白表达有关.     

普罗布考对心肌梗死大鼠心肌组织Bcl-2和Bax表达及氧化应激的影响

背景 心肌梗死后心肌细胞凋亡与氧化应激有关,普罗布考为脂溶性强抗氧化剂,实验证明具有保护心肌细胞的作用,该药保护心肌细胞的作用是否通过调控细胞凋亡相关基因Bcl-2和Bax目前尚不清楚.目的 研究普罗布考对心肌梗死大鼠心肌组织Bcl-2和Bax表达及氧化应激的影响.方法 将心肌梗死后24 h存活大鼠41只随机分为2组:盐水组(5 mL/d,n=20),普罗布考组[60 mg/(kg·d),n=21],灌胃给药;另设假手术组(n=12)作对照.分别于心肌梗死后6周:导管法测定左室有创血流动力学指标,TUNEL法检测非梗死区心肌细胞凋亡;RT-PCR的方法观察心肌组织Bcl-2及Bax mRNA表达的变化;Western blot检测心肌Bcl-2及Bax蛋白表达;比色法测定心肌组织氧化代谢指标.结果 (1)与假手术组相比,所有心肌梗死大鼠均出现显著的Bcl-2 mRNA及蛋白表达降低,Pax mRNA及蛋白表达与心肌细胞凋亡指数显著升高(P均＜0.01).与盐水组相比,普罗布考组心肌组织Bcl-2 mRNA及蛋白表达显著升高,Bax mRNA及蛋白表达及心肌细胞凋亡指数显著降低(P均＜0.01);(2)与假手术组相比,所有心肌梗死大鼠心肌组织均出现显著的MDA升高,SOD、TAOC含量及SOD/MDA比值降低(P均＜0.01);与盐水组相比,普罗布考组MDA显著下降,SOD、TAOC含量及SOD/MDA均升高(P均＜0.01);心肌细胞凋亡指数与TAOC、SOD/MDA比值呈负相关(P均＜0.01).结论 心肌梗死后心肌细胞凋亡增加,普罗布考治疗可以抑制心肌细胞凋亡,降低心肌梗死后心肌组织的氧化应激.     

罗格列酮对大鼠心肌缺血再灌注损伤的保护作用

目的 观察罗格列酮对大鼠在体心肌缺血再灌注损伤及心肌细胞凋亡的影响.方法 采用结扎大鼠左冠状动脉前降支30 min,再灌注60 min的方法 ,复制大鼠心肌缺血再灌注损伤模型.实验动物随机分为罗格列酮组(3 mg·kg-1·d-1)、模型组(生理盐水2ml/d)和假手术组(生理盐水2ml/d).再灌注后观察血清酶学改变,Evans blue、TTC双重染色检测心肌梗死面积,流式细胞术测定心肌细胞凋亡指数,免疫组化检测凋亡蛋白Bcl-2、Bax表达.结果 与模型组比较,罗格列酮显著降低血清酶CK、LDH水平(P＜0.01),缩小心肌梗死面积(P＜0.01),增加Bcl-2、减少Bax表达(P＜0.01),减少心肌细胞凋亡(P＜0.01).结论 罗格列酮对心肌缺血再灌注损伤有保护作用.     

芪参益气滴丸对急性心肌梗死大鼠心肌细胞凋亡及心功能的影响

目的 研究芪参益气滴丸(QS)对急性心肌梗死(AMI)大鼠心肌细胞凋亡及心功能的影响.方法 结扎左冠状动脉前降支建立大鼠AMI模型,将30只SD大鼠随机分为假手术组、AMI组、QS治疗组,QS治疗组给予0.135g.kg-1.d-1)的QS混浊液灌胃4w,治疗结束后检查3组大鼠血流动力学,处死大鼠,采用原位末端标记(TUNEL)法检测心肌细胞凋亡指数,采用免疫组化法测定Bcl-2及Bax蛋白表达.结果 与假手术组、AMI组相比,QS治疗组血流动力学指标明显改善(P ＜0.05);Bax蛋白表达升高,Bcl-2蛋白表达降低,心肌细胞凋亡指数显著降低(P＜0.05).结论 QS可通过多种途径有效减少其心肌细胞凋亡,从而改善AMI大鼠的心功能.     

利心冲剂对心衰大鼠血流动力学和凋亡相关基因表达的影响

目的观察利心冲剂对心衰大鼠血流动力学的影响,探讨其抑制心肌细胞凋亡的分子机制。方法 50只Wistar大鼠随机分为5组:正常组、模型组、卡托普利治疗组、利心冲剂低剂量组、利心冲剂高剂量组。采取腹腔注射阿霉素(ADR,4mg/kg,每5天一次,共3次)复制大鼠心衰模型,观察心肌细胞病理学、血流动力学及凋亡相关基因Bcl-2、Bax表达的变化。结果与模型组比较,利心冲剂治疗组光镜下心肌损伤明显减轻;左室收缩压明显升高,左室舒张末压明显降低;抑制凋亡作用的Bcl-2基因表达增高、Bax/Bcl-2降低(P<0.05)。结论利心冲剂能改善心衰大鼠心功能及抑制心肌细胞凋亡,其机制可能与上调Bcl-2基因表达及降低Bax/Bcl-2比值有关。     

血管肽酶抑制剂对心力衰竭大鼠心肌细胞凋亡和心室重构的影响

目的研究心肌细胞凋亡和心室重构在心力衰竭发展中的变化及血管内肽酶抑制剂的干预作用,探讨血管内肽酶抑制剂治疗心力衰竭的机制.方法选用雄性SD大鼠,随机分为假手术组,心肌梗死组(MI组)和心肌梗死后Omapatrilat(OMA)干预组(MI OMA组).经冠脉前降支结扎术建立心肌梗死模型,术后24 h MI OMA组大鼠给予Omapatrilat 40 mg/kg·d,饮水给药,假手术组和MI组大鼠饲普通饮水.术后4、6周检测大鼠非心肌梗死区心肌细胞凋亡指数;Western蛋白印迹检测心肌细胞凋亡加速基因Bax和凋亡抑制基因Bcl-2的蛋白表达水平;VG染色测胶原容积分数(CVF);压力传感器记录左室血流动力学改变.结果 (1)术后非心肌梗死区心肌细胞凋亡指数,MI组及MI OMA组均显著高于假手术组(4周,3.8%±1.0%,2.6%±1.0%vs 0.1%±0.1%,P＜0.01;6周,4.1%±1.3%,2.5%±0.9%vs 0±0,P＜0.01),但MI OMA组显著低于MI组(4周,P＜0.05;6周,P＜0.01);(2)与假手术组相比,MI组和MI OMA组术后的Bax蛋白表达量均显著增高(4周,321.3%±17.5%,174.6%±13.9%vs 100.0%±8.3%,P＜0.01;6周,362.3%±21.0%,193.9%±19.6%vs 104.7%±10.6%,P＜0.01),但MI OMA组显著低于MI组(P＜0.01);MI组和MI OMA组的Bcl-2蛋白表达量均低于假手术组(4周,79.3%±7.9%,86.6%±4.9%vs 100.0%±5.9%,P＜0.01;6周,76.6%±9.3%,84.7%±3.4%vs 97.1%±6.0%,P＜0.01),而MI OMA组高于MI组(P＜0.05);(3)MI OMA组非梗死区CVF明显低于MI组(4周,10.5%±0.7%vs 14.7%±1.18%,P＜0.01;6周,11.9%±1.4%vs 15.7%±1.1%,P＜0.01),但仍显著高于假手术组(4周,10.5%±0.7%vs 3.9%±.1%,P＜0.01;6周,11.9%±1.4%vs 3.9%±1.2%,P＜0.01);(4)MI组和MI OMA组大鼠4周和6周的心功能明显降低(与假手术组比,P＜0.05),而MI OMA组大鼠的心功能显著改善(与MI组比,P＜0.01).结论血管肽酶抑制剂可通过调节凋亡相关基因Bax和Bcl-2的蛋白表达,减少心肌细胞凋亡,抑制心肌间质纤维化,从而减轻慢性心力衰竭阶段的心室重构,进而改善心功能.     

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.     

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.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.