心脏收缩力调节对慢性心力衰竭兔心肌重构的影响

目的:观察心脏收缩力调节(CCM)对慢性心力衰竭(心衰)兔心肌重构的影响并探讨其可能机制。方法:选取新西兰大白兔30只,分为假手术组、心衰组、心衰+CCM组,各组均n=10。假手术组仅开胸,未行升主动脉套扎。心衰组、心衰+CCM组通过升主动脉根部套扎法建立兔慢性心衰模型,心衰+CCM组模型制作成功后给予4周的CCM治疗。分别于实验第12周末和(或)第16周末对各组实验动物,采用超声心动图检测心脏功能,Masson染色评价心肌组织纤维化及病理形态改变,采用酶联免疫吸附法(ELISA)检测血浆B型利钠肽(BNP)水平,蛋白免疫印迹(Westernblot)法检测心肌组织I型胶原蛋白、Ⅲ型胶原蛋白、基质金属蛋白酶(MMP)2、MMP9、MMP抑制因子(TIMP)1、半乳糖凝集素3蛋白表达水平。结果:(1)超声心动图结果:实验第12周末与假手术组相比,心衰组、心衰+CCM组左心室收缩末内径(LVESD)、左心室舒张末内径(LVEDD)明显扩大,左心室缩短率(LVFS)和左心室射血分数(LVEF)明显下降(P0.05);实验第16周末,与心衰组相比,心衰+CCM组的LVESD、LVEDD、LVEF、LVFS指标明显改善(P0.05)。(2)病理学改变:Masson染色示与假手术组相比心衰组心肌组织胶原纤维含量明显增加(P0.05),CCM可部分减轻心衰心肌组织的胶原纤维沉积(P0.05)。(3)实验第12周末,与假手术组相比,心衰组、心衰+CCM组血浆BNP水平明显升高(P0.05)。实验第16周末,与心衰组相比,心衰+CCM组的血浆BNP水平下降,但仍高于假手术组(P0.05)。(4)Western blot法检测结果:心衰组心肌组织中I型胶原蛋白、Ⅲ型胶原蛋白、MMP2、MMP9、TIMP1、半乳糖凝集素3的蛋白表达水平明显高于假手术组(P0.05),心衰+CCM组心肌组织中I型胶原蛋白、Ⅲ型胶原蛋白、MMP2、MMP9、TIMP1、半乳糖凝集素3的蛋白表达水平较心衰组明显下降(P0.05),但仍高于假手术组(P0.05)。结论:心脏收缩力调节可以改善慢性心衰兔心功能及心肌重构,其机制可能与下调心衰心肌组织中I型胶原蛋白、Ⅲ型胶原蛋白、MMP2、MMP9、TIMP1、半乳糖凝集素3蛋白的表达有关。     

抑制JAK/STAT信号通路对心力衰竭大鼠心功能的 影响抑制JAK/STAT信号通路对心力衰竭大鼠心功能的 影响

目的：通过使用AG490抑制JAK/STAT信号通路探讨抑制该通路对心力衰竭大鼠血流动力学及BNP的影响。方法：实验大鼠随机分为3组，对照组(n=15)；心力衰竭组(n=15)，缩窄腹主动脉直径至0.45mm；AG490药物干预组(n=15)，腹主动脉缩窄术后每周经腹腔注射AG490。术后观察大鼠生存情况，分别在4周和8周后应用超声心动图检测IVSd 、LVPWd 、LVEDd、LVEDs和LVEF，并于第8周测量BNP的变化。结果：4周时心衰组大鼠IVSd、LVPWd、LVEDs、LVEDd、LVEF与对照组和AG490干预组均有差异(P<0.05)，IVSd、LVEDd、LVEF干预组和对照组差异无统计意义(P>0.05)。8周时3组大鼠各项超声检测指标均有明显差异(P<0.05)，心衰组变化更明显(P<0.05)。心衰组大鼠血清BNP明显高于其余两组(P<0.01)，AG490干预组BNP高于对照 组，低于心衰组，差异具有统计学意义 (P<0.05)。结论： JAK/STAT信号通路参与慢性心力衰竭进程，干预JAK/STAT信号通路可减轻腹主动脉缩窄大鼠心力衰竭的严重程度。     

芪苈强心对阿霉素致心肌病大鼠心功能及血清因子的影响

目的:初步探讨芪苈强心胶囊对阿霉素致心肌病大鼠心功能及血清因子的影响及其机制。方法:将29只SD大鼠中9只作为正常对照组,20只用作造模。造模大鼠2周内分6次腹腔注射阿霉素2.5mg/kg作为心力衰竭(心衰)模型后,分为心衰组、芪苈强心组和美托洛尔组,后2组分别服用芪苈强心胶囊生粉(1g/kg)和美托洛尔(10mg/kg)治疗6周,正常对照组和心衰组以相同体积0.9%氯化钠溶液灌胃6周。超声心动图检测各组大鼠心功能指标,ELISA法检测大鼠血清肿瘤坏死因子-α(TNF-α)和B型钠尿肽(BNP)含量,心肌组织苏木素-伊红染色病理检验。结果:心衰组较正常对照组心功能显著降低,左心室收缩末期内径(LVESD)和左心室舒张末期内径(LVEDD)显著增加(P<0.01和P<0.05),左室射血分数(LVEF)和短轴缩短率(FS)显著降低(均P<0.01),血清BNP和TNF-α水平明显升高(均P<0.01)。美托洛尔组较心衰组显著改善了大鼠的LVESD、LVEDD、LVEF和FS(均P<0.05),BNP显著低于心衰组(P<0.05)。芪苈强心组较心衰组也改善了大鼠LVEF和FS(均P<0.05),显著降低心衰大鼠血...     

心力衰竭患者脑钠素水平与心功能的关系

【目的】研究慢性心力衰竭患者血清脑钠素(BNP)浓度与心功能的关系。方法用酶联免疫吸附法(ELISA)测定62例慢性心力衰竭患者及20名健康对照组血清BNP浓度,采用多普勒超声心动图测定左室射血分数(LVEF)、左室短轴缩短率(FS)、左室舒张末内径(LVEDD),观察BNP水平与LVEF、FS、LVEDD的相关性。结果心衰组血清BNP浓度较对照组明显增高(P<0.01),各心衰组BNP水平差异有统计学意义,且BNP水平随NYHA分级升高而升高。BNP水平与LVEF及FS呈负相关(r=-0.62,r=-0.59,P<0.01),与LVEDD呈正相关(r=0.67,P<0.01)。结论血清CNP浓度可作为反映心功能状态的指标,并与心脏结构有关。     

B型钠尿肽在大鼠心肌纤维化中的变化及卡维地洛的干预作用

目的研究异丙基肾上腺素(ISO)诱导的大鼠心肌纤维化过程中血清B型钠尿肽(BNP)和心肌BNP mRNA表达变化的意义,以及β-受体阻断剂卡维地洛的干预作用。方法将46只SD大鼠随机分为4周模型组(n=10)、8周模型组(n=9)、卡维地洛组(n=11)、4周对照组(n=8)和8周对照组(n=8)。模型组及卡维地洛组大鼠给予皮下注射ISO 10mg.kg-1.d-1,两个对照组给予皮下注射等量0.9%氯化钠溶液,共7d,至4周时,将4周模型组和4周对照组大鼠处死,同时卡维地洛组开始给予卡维地洛10mg.kg-1.d-1灌胃,8周模型组和8周对照组给予等量蒸馏水灌胃,共4周,至第8周末处死剩余大鼠,各组大鼠均测心重指数(HWI),MASSON染色后测心肌胶原积分(CVF),ELISA法检测血清中BNP水平,RT-PCR法检测心肌BNP的mRNA表达。结果 4周模型组HWI、CVF、血清BNP水平及心肌BNP mRNA表达较4周对照组升高,差异有统计学意义(P<0.01);8周模型组较4周模型组上述指标均升高,差异有统计学意义(P<0.01)。血清BNP与心肌BNP mRNA表达呈正相关(r=0.647,P<0.01)。卡维地洛组与8周模型组比较,上述指标水平均下降,差异有统计学意义(P<0.01)。结论 BNP可作为心肌纤维化早期诊断和严重程度的指标,卡维地洛可以有效改善心肌纤维化严重程度,降低血清BNP水平,使BNP的表达量降低。     

络风宁2号方对心肌梗死后心力衰竭大鼠心功能和心肌纤维化的影响

目的观察络风宁2号方对心肌梗死(心梗)后心力衰竭(心衰)大鼠心功能和心肌纤维化进程的影响及其可能的药理机制。方法采用左冠状动脉前降支结扎法制作心梗后慢性心衰模型,雄性SD大鼠56只随机分为模型组6只,卡托普利组6只,络风宁2号方低剂量组6只,络风宁2号方中剂量组7只,络风宁2号方高剂量组6只,假手术组5只,造模手术存活率86%,造模成功率70%,假手术组大鼠存活率83.3%。络风宁2号方低中高剂量组及卡托普利组连续给药4周,其他组灌服生理盐水4周后,超声心动图检测各组大鼠心脏结构及心功能、ELISA法检测大鼠血清N末端脑钠肽前体(NT-proBNP)水平、Masson染色法观察大鼠心肌纤维化情况并测算胶原容积分数(CVF)。结果和模型组比较,络风宁2号方各剂量组、卡托普利组大鼠一般情况有所改善,左室舒张末期内径(LVDd)、左室收缩末期内径(LVDs)降低(P<0.05),左室射血分数(LVEF)升高(P<0.05),血清NT-proBNP水平、CVF明显下降,差异具有统计学意义(P<0.05或P<0.01),且在一定范围内同剂量呈正相关;卡托普利组和络风宁2号高剂量组之间NT-proBNP水平和心肌细胞纤维化程度比较的差异均无统计学意义(P>0.05)。结论络风宁2号方有较好的改善心衰大鼠心功能和抗心肌纤维化的作用,且此作用在一定范围内同剂量呈正相关,同时高剂量络风宁2号方和卡托普利改善CHF大鼠心功能和抗心肌纤维化的作用相当。     

益气温阳活血利水药对心肌梗死后心力衰竭大鼠心功能和脑钠肽的影响

目的观察益气温阳活血利水中药不同配伍对心肌梗死后心力衰竭（心衰）大鼠不同时相血清脑钠肽（BNP）和心功能的影响。方法结扎大鼠冠状动脉左前降支,制作大鼠心肌梗死后心衰模型,并分别于心衰早期和心衰期使用益气温阳活血利水中药不同配伍进行干预,检测干预后大鼠心功能、血清脑钠肽水平。结果和假手术组相比,各模型组心功能明显下降,血清脑钠肽明显升高。干预后,在心衰早期和心衰期,益气温阳活血利水组心功能均明显优于其他中药组和阳性对照组（P〈0.05）,脑钠肽水平则明显低于其他中药组和阳性对照组（P〈0.05）。在心衰早期,活血利水组心功能稍优于空白组,脑钠肽水平亦较低,但均无统计学意义（P〉0.05）,而在心衰期则有统计学意义（P〈0.05）。结论益气温阳活血利水中药可降低心肌梗死后心衰大鼠血清脑钠肽水平并改善其心功能,在心衰早期和心衰期均以益气温阳活血利水相配伍为最佳。     

去肾交感神经术对自发性高血压大鼠中枢促丝裂原活化蛋白激酶及核转录因子κB的影响

目的通过对自发性高血压大鼠(SHR)行去肾交感神经术(RDN),观察RDN对血压的影响,以及探究RDN对下丘脑丝裂原活化蛋白激酶(MAPK)及核转录因子κB(NF-κB)的影响。方法选取SHR 36只及同周龄WKY大鼠12只;将36只SHR随机分为3组,即SHR基线组、RDN组(分为D1和D6组)、假手术组(分为S1和S6组),每组各12只;将12只WKY大鼠作为基线对照组(WKY组)。于12周龄时对RDN组及假手术组SHR分别进行RDN及假手术。D1组及S1组于手术后1周(各亚组n=6)、D6组及S6组于手术后6周(各亚组n=6)处死大鼠。分别于基线,术后1、6周测量各组大鼠血压,检测血浆神经元特异性烯醇化酶(NSE)水平,下丘脑p38MAPK、p-p38MAPK、p65NF-κB含量,D6、S6组测量1~6周血压。结果 RDN术后1~5周,D6组大鼠收缩压及舒张压下降,D1组大鼠的血压较S1组显著降低(P0.05),且较SHR基线明显降低(P0.05)。D6组大鼠的血压与S6组比较差异无统计学意义(P0.05),且与SHR基线组比较差异无统计学意义(P0.05)。D1组大鼠血浆NSE较S1组升高(P0.05),且较SHR基线组升高(P0.05),但D6组血浆NSE与SHR基线组及S6组比较差异无统计学意义(P0.05)。D1组大鼠下丘脑p38MAPK、p-p38MAPK、p65NF-κB蛋白和mRNA表达较S1组显著降低(P0.05),且较SHR基线组显著降低(P0.05)。D6组p38MAPK、p-p38MAPK、p65NF-κB蛋白和mRNA表达在RDN术后6周较S6组仍显著降低(P0.05),但与SHR基线组比较差异无统计学意义(P0.05)。结论 RDN可显著降低SHR血压,并且能够降低下丘脑MAPK及NF-κB水平。     

缺血性心脏病合并左心衰竭患者血清脑钠肽和内皮素-1的变化

目的观察缺血性心脏病(IHD)合并左心衰竭(LHF)患者血清B型脑钠肽(BNP)、内皮素-1(ET-1)水平及其临床意义。方法将40例IHD患者分成两组,心力衰竭组25例和心功能代偿组15例,分别与对照组20例比较。测定3组入院时BNP、ET-1水平。结果心力衰竭组与心功能代偿组的BNP、ET-1均明显高于对照组,LVEF明显低于对照组,且有心力衰竭组BNP、ET-1明显高于心功能代偿组,差异有统计学意义(P<0.05),但心力衰竭组LVEF与心功能代偿组比较差异无统计学意义(P>0.05)。结论 BNP、ET-1水平可作为IHD合并LHF患者诊断及判断预后的观察指标。     

阿托伐他汀对冠心病心力衰竭患者血浆钠尿肽水平及心功能的影响

目的:观察阿托伐他汀对冠心病心力衰竭(心衰)患者血浆钠尿肽(BNP)水平和心功能的影响。方法:将128例冠心病心衰(心功能Ⅱ～Ⅲ级)患者随机分为10mg阿托伐他汀组(A组)、20mg阿托伐他汀组(B组)和对照组(C组),3组均给予抗心衰基础治疗,A组加服阿托伐他汀10mg/d,B组加服阿托伐他汀20mg/d。治疗前及治疗后12周时测定血浆BNP、血清高敏C反应蛋白(hs-CRP)水平、6min步行试验,并采用超声心动图测量左心室射血分数(LVEF)。结果:3组患者治疗12周时心功能指标、血浆BNP水平及血清hs-CRP水平均较治疗前明显改善,2种剂量治疗组血浆BNP、血清hs-CRP水平均降低,LVEF均升高,与对照组比较差异有统计学意义(P<0.01)。A、B治疗组的6min步行距离明显增加,与对照组比较,差异有统计学意义(P<0.05);而A、B治疗组间血浆BNP水平、血清hs-CRP水平、LVEF及6min步行距离无差异。结论:冠心病心衰患者在基础治疗上加用小剂量阿托伐他汀即可以降低BNP水平及血清hs-CRP水平,进一步改善心功能,抑制心肌微炎症可能是该药机制之一。     

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.