丙酮酸对缺血/再灌注大鼠心肌的保护作用

目的:探讨丙酮酸(Pyr)对缺血/再灌注(I/R)大鼠心肌的影响及其可能的机制。方法:30只SD成年大鼠随机分为假手术(Sham)组、I/R组及I/R+Pyr组,每组10只。I/R+Pyr组大鼠于再灌前5 min,开始持续性静脉灌注Pyr 2 h[25 mg/(kg·h)]。再灌注2 h后,利用多道生理记录仪检测大鼠在体血流动力学指标:平均动脉压(MABP)、左室收缩压(LVSP)及左室最大收缩、舒张末压微分(±LV dP/dt max)。采用Western blot方法检测磷酸化-JNK(p-JNK)和总的JNK(t-JNK)表达。用原位缺口末端标记法(TUNEL)评价心肌细胞的凋亡。结果:I/R组的MABP、LVSP、±LV dP/dt max显著低于Sham组(P0.01),Pyr干预可增加I/R后MABP、LVSP及±LV dP/dt max的水平(P0.05)。与Sham组相比,I/R组大鼠左心室p-JNK的水平明显增高(P0.01);而Pyr可降低大鼠左心室p-JNK的水平(P0.01),并抑制心肌细胞凋亡(P0.05)。结论:Pyr可改善I/R大鼠心肌的功能,抑制心肌细胞凋亡,其机制可能与抑制JNK信号的激活有关。     

欣力胶囊抑制Ang-Ⅱ刺激引起的心肌细胞肥大

目的欣力胶囊为中德实验室自主开发的治疗心力衰竭的药物。本实验将明确欣力胶囊是否能够抑制AngiotensinⅡ刺激引起的心肌细胞肥大。方法以欣力胶囊灌胃大鼠,7 d后取大鼠血清进行细胞水平的血清药理学实验。AngiotensinⅡ刺激原代培养的心肌细胞,分组为:正常对照、AngiotensinⅡ阳性对照、欣力胶囊对照和欣力胶囊药效观察组,其中药效观察组再按照不同剂量分为六组。培养24 h以后,通过3 h掺入实验、蛋白含量测定和细胞表面积计算三种方法确定心肌细胞肥大状态。结果AngiotensinⅡ刺激以后,细胞[3H]摄入量、蛋白含量和细胞表面积均明显增加 (P<0．01)。欣力胶囊能够显著抑制AngiotensinⅡ引起的心肌细胞肥大(vs．AngiotensinⅡ阳性对照,P<0．01)。结论欣力胶囊能够抑制AngiotensinⅡ刺激引起的心肌细胞肥大,从而抑制心肌重塑发生,可能是欣力胶囊治疗心力衰竭的机制之一。     

辛伐他汀减轻舒张功能不全心力衰竭大鼠心肌纤维化

目的 探讨辛伐他汀对舒张功能不全心力衰竭(diastolic heart failure,DHF)大鼠心脏功能保护和心肌纤维化的影响.方法 雄性SD大鼠30只,随机分为阴性对照组、DHF组、辛伐他汀组.采用腹主动脉缩窄建立DHF模型,阴性对照组只开腹和分离腹主动脉.辛伐他汀组大鼠术后经灌胃给予辛伐他汀2 mg/(kg·d),阴性对照组和DHF组大鼠给予同等量的生理盐水.4周末心脏超声检测心功能,颈动脉插管记录血流动力学,HE染色和Masson染色观察心肌组织病理结构的变化.结果 心脏超声显示DHF组大鼠室间隔和左心室后壁厚度、E/A比值明显增高,血流动力学检测显示收缩压、舒张压、左心室收缩压、左心室舒张末压升高,左心室松弛时间常数延长,左心室内压最大下降速率下降,心脏指数和左心室质量指数增加.辛伐他汀使增加的室间隔和左心室后壁厚度、E/A、收缩压、舒张压、左心室收缩压、左心室舒张末压、心脏指数和左心室质量指数降低,左心室松弛时间常数缩短,左心室内压最大下降速率升高.HE染色和Masson染色显示,DHF组大鼠心肌组织间纤维组织和炎性细胞增多,心肌胶原面积与总面积的比值和壁内小动脉管腔周围胶原面积与管腔面积的比值在心肌组织中显著增加;辛伐他汀减轻DHF大鼠心肌组织间纤维化和炎性细胞浸润,降低心肌胶原面积与总面积的比值以及壁内小动脉管腔周围胶原面积与管腔面积的比值.结论 辛伐他汀改善DHF大鼠心脏功能,此作用可能与减轻心室纤维化有关.     

阿托伐他汀对兔舒张性心力衰竭模型心室重构的影响

目的:研究阿托伐他汀改善舒张性心力衰竭(心衰)心室重构的作用.方法:30只新西兰白兔随机分为3组,舒张性心衰组(n=10,腹主动脉缩窄术),阿托伐他汀组[n=10,腹主动脉缩窄术后给予阿托伐他汀5mg/(kg·d)],假手术组(n=10,进行假手术操作);通过心脏超声和血流动力学检查比较3组心功能的差异,通过心肌胶原含量测定(羟脯氨酸法)和天狼猩红染色(PRS)测定胶原面积(CA)、容积分数(CVF)及Ⅰ和Ⅲ型胶原的面积比值比较3组间质重构的差异.结果:心脏超声检查显示,术后12周与假手术绢比较,舒张性心衰组室间隔厚度、左心室后壁厚度明显增厚,二尖瓣舒张早期血流峰值/舒张晚期血流峰值下降,等容舒张期时间延长;左心室舒张末压升高,等容舒张期松弛时间常数延长,左心室重量/体重增高,肺脏重量/体重增高;胶原含量增高,胶原面积增大,胶原容积分数升高及Ⅰ型和Ⅲ型胶原面积比例升高,差异均有统计学意义(P<0.05或P<0.01).阿托伐他汀组上述指标(除左心室重量/体重)与舒张性心衰组比较差异均有统计学意义(P<0.05或P<0.01).结论:阿托伐他汀可以明显改善心室重构,延缓整个舒张性心衰的病程.     

艾司洛尔对脓毒症大鼠心肌细胞β肾上腺能受体及血流动力学的影响

目的通过观察艾司洛尔对脓毒症大鼠心肌细胞β肾上腺能受体及心脏血流动力学的影响。方法随机将60只大鼠分为假手术组、脓毒血症组、艾司洛尔组,每组20只。采用盲肠穿孔结扎术制备脓毒症大鼠模型。各组术后分别予以相应措施。观察术后6、12、18 h的平均动脉压(MAP)、心率(HR)、左室舒张末压(LVEDP)、左心室收缩压(LVSP)、左心室最大收缩速率(+dP/dt)、左室最大舒张速率(-dP/dt)。结果与假手术组比较,脓毒症大鼠手术后6 h始即出现MAP的明显下降(P<0.01)。艾司洛尔组的MAP 6 h时与脓毒血症组大鼠有提高,随着时间延长,差异逐渐增大,12 h开始P<0.01。脓毒症组大鼠术后6 h HR较假手术组略有增高,12 h时HR即开始明显降低(P<0.01),而艾司洛尔组6 h时HR与脓毒症组差异无统计学意义(P>0.05),但自12 h开始HR较脓毒症组明显提高(P<0.05)。与假手术组比较,脓毒症大鼠的LVEDP、LVSP、+dP/dt及-dP/dt自6h始即出现均降低,而艾司洛尔组各项指标比脓毒症组显著提高(P<0.01)。另外假手术组和脓毒症模型组各时间点β肾上腺能受体活性均无明显变化;对应时点脓毒症模型组合艾司洛尔组β肾上腺能受体活性明显较假手术组低(P<0.05);0.5 h艾司洛尔组β肾上腺能受体活性明显高于脓毒症模型组(P<0.05)。结论艾司洛尔用于辅助治疗脓毒症可有助于稳定HR,改善心脏血流动力学,其可能是通过激活心肌β肾上腺素能受体-环磷酸腺苷系统起到改善心功能,保护心肌细胞的作用。     

扩张型心肌病大鼠模型心肌结构与心功能的变化

目的探讨扩张型心肌病大鼠胶原重塑及其与心功能的关系.方法用呋喃唑酮饲养Wistar大鼠建立扩张型心肌病(DCM)大鼠模型, 超声心动图检测大鼠左心室舒张期末内径(LVED)、左心室收缩期末内径(LVES)、左心室内径缩短率(FS)及左心室射血分数(LVEF);右心导管测压,HE染色观察大鼠心肌细胞形态学变化;VG和免疫组化染色检测心肌胶原纤维及胶原容积分数(CVF).结果①与正常对照组相比,DCM组大鼠心脏LVED(cm)和LVES(cm)均明显增大、FS(%)和LVEF(%)均明显下降,左心室内径增大、游离壁变薄,心脏重量/体重比值增加,右房压明显增高(均P>0.05).②DCM大鼠心肌细胞肥大,变性,间质胶原纤维明显增多,间质胶原CVF及Ⅰ、Ⅲ型胶原的含量明显增加.结论 DCM大鼠心肌间质胶原网络重塑影响左室功能.     

扩张型心肌病大鼠模型心肌结构与心功能的变化

目的　探讨扩张型心肌病大鼠胶原重塑及其与心功能的关系。方法 用呋喃唑酮饲养Wistar大鼠建立扩张型心肌病(DCM)大鼠模型, 超声心动图检测大鼠左心室舒张期末内径(LVED)、左心室收缩期末内径(LVES)、左心室内径缩短率(FS)及左心室射血分数(LVEF);右心导管测压,HE染色观察大鼠心肌细胞形态学变化;VG和免疫组化染色检测心肌胶原纤维及胶原容积分数(CVF)。结果 ①与正常对照组相比,DCM组大鼠心脏 LVED(cm)和 LVES(cm)均明显增大、FS(%)和LVEF(%)均明显下降,左心室内径增大、游离壁变薄,心脏重量/体重比值增加,右房压明显增高(均P>0 .05)。②DCM大鼠心肌细胞肥大,变性,间质胶原纤维明显增多,间质胶原 CVF及Ⅰ、Ⅲ型胶原的含量明显增加。结论 DCM大鼠心肌间质胶原网络重塑影响左室功能。     

肝细胞生长因子对犬急性心肌梗死后左心室重构的影响

目的探讨肝细胞生长因子(hepatocyte growth factor,HGF)对急性心肌梗死后左心室重构的影响。方法将12只杂种犬结扎左冠状动脉前降支,复制急性心肌梗死模型,随机分为2组:对照组和治疗组,每组6只。治疗组于梗死心肌周围注射pc-DNA3-HGF基因1 ml,对照组给予等量的生理盐水。分别于术后1、4、8周进行超声心动图检查,检测心功能、左心室重构指标。术后8周取心肌组织行HE染色及天狼猩红染色,图像分析系统测定Ⅰ、Ⅲ型胶原含量。结果术后4周时,治疗组左心室射血分数(LVEF)明显高于对照组(P<0.05)。8周时,LVEF明显升高,左心室舒张末容积较对照组降低(P<0.05)。对照组组内比较显示左心室后壁厚度显著降低(P=0.04)。HE染色可观察到治疗组梗死心肌周围毛细血管较对照组增多,而对照组瘢痕形成明显。天狼猩红染色显示治疗组Ⅲ型胶原含量高于对照组,Ⅰ/Ⅲ型胶原比例低于对照组(P<0.05)。结论HGF可能通过减少胶原的沉积及促进血管增生,减少心肌坏死及瘢痕形成,从而改善心功能及急性心肌梗死后的左心室重构。     

肿瘤坏死因子α在大鼠心肌梗死后心肌间质重塑和心力衰竭中的作用

目的:探讨心肌梗死后大鼠心肌肿瘤坏死因子α表达、基质金属蛋白酶(MMPs)及基质金属蛋白酶组织抑制剂(TIMPs)变化与心肌胶原代谢和心功能改变之间的相互联系.方法:结扎大鼠冠状动脉前降支复制心肌梗死模型,为心肌梗死组.同时设假手术组,分别于术后4周、8周、12周行血流动力学检测,称取心脏组织湿重.对非梗死区心肌组织采用逆转录-多聚酶链反应(RT-PCR)法检测肿瘤坏死因子α信使核糖核酸(mRNA)表达,Western-blot法检测中性粒细胞胶原酶(MMP-8)、明胶酶(MMP-9)及TIMP-1蛋白表达,明胶酶谱法检测明胶分解活性和天狼猩红染色偏振光下检测心肌胶原含量.结果:①心肌梗死组较同期假手术组左心室舒张末压均显著增加(P＜0.05),平均动脉压、左心室内压最大上升和下降速率则显著降低,有极显著性差异(P＜0.01);除12周组左心室相对重量外,其余时相左心室相对重量和右心室相对重量均显著增加(P＜0.05).②心肌梗死组不同时相心肌较同期假手术组肿瘤坏死因子α mRNA显著增加,呈时间依赖性;MMP-8、MMP-9蛋白表达及MMP明胶酶分解活性均较同期假手术组明显增加,而TIMP-1差异无显著性(P＞0.05);心肌胶原含量增加,与心功能呈负相关.结论:肿瘤坏死因子α基因过度表达与MMPs蛋白表达增加及其活性增强变化相一致,心肌肿瘤坏死因子α表达增加可能是心肌梗死后心肌间质重塑和心力衰竭发生发展的重要机制之一.     

神经胶质细胞生长因子-1β对慢性心衰大鼠心功能及促血管生成素、大麻素受体、蛋白激酶C表达的影响

目的分析神经胶质细胞生长因子-1β(neuregulin-1β)对慢性心衰大鼠心功能及促血管生成素(Ang2)、大麻素受体(CB1)、蛋白激酶C(PKC)表达的影响。方法将30只雄性SD大鼠随机分成正常组、模型组、neuregulin-1β干预组(each n=10)。采用尾静脉注射阿霉素(20 mg/kg)的方法建立慢性心衰大鼠模型,并通过心脏超声确定模型成功。干预组于建模成功后连续1周每天尾静脉给予neuregulin-1β(10μg/kg·d),正常组给予与模型组等体积的生理盐水。三组大鼠均于实验第9周行大鼠心脏超声及血流动力学检测,取心肌组织进行HE染色进行病理学检测,采用Western blotting法检测三组大鼠心肌组织中PKC蛋白量,采用免疫组织化学法检测三组大鼠心肌组织中Ang2、CB1蛋白相对表达量。结果模型组和neuregulin-1β干预组在第8周心脏超声指标均显示慢性心衰大鼠模型建立成功。neuregulin-1β干预1周后,与模型组比较,干预组的心脏超声指标左心室舒张末期内径、左心室收缩末期内径均显著性降低(P0.05),左室缩短率与左室射血分数均显著性升高(P0.05);血流动力学指标左心室收缩压(LVSP)、左心室内压最大上升速率、左心室内压最大下降速率均显著性升高(P0.05),左心室舒张末期压显著性降低(P0.05);PKC相对蛋白量显著减少(P0.05);Ang2和CB1阳性区域评分明显降低(P0.05);同时病理结果显示,neuregulin-1β干预组较模型组心肌病变较轻,除部分心肌水肿外,未见明显的心肌细胞坏死、炎证浸润及明显的血管充血扩张。结论 neuregulin-1β的干预显著改善大鼠心肌细胞的病变情况,其作用机制可能与下调PKC蛋白及Ang2、CB1的表达有关。     

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.