肾上腺髓质素2对自发性高血压大鼠血压和心功能的影响

背景 肾上腺髓质素2(AM2)是超降钙素/降钙素基因相关肽(CGRP)家族的新成员.该家族已有成员包括降钙素基因相关肽、肾上腺髓质素(ADM)、降钙素和胰岛淀粉样多肽.目前研究结果表明,AM2参与了心血管功能的调节.目的研究外源性给予AM2对自发性高血压大鼠(SHR)血压和心功能的影响及可能机制.方法 将24只11周龄雄性SHR随机分为对照组(n=8)、ADM组(n=8)及AM2组(n=8).通过微量渗透泵皮下持续给予ADM和AM2,剂量均为500 ng/(kg·h).埋泵两周后,采用心室导管的方法测定血压和心功能的变化,RT-PCR方法测定心肌中脑钠素(BNP)和心钠素(ANP)的mRNA表达.结果 1)与对照组相比,AM2组的收缩压和左室内压上升、下降最大速率(±LV dp/dtmax)以及左心室收缩压(LVSP)均显著降低(P＜0.01);2)AM2组心肌中ANP和BNP的mRNA表达较对照组显著增加(P＜0.01).结论 采用微量渗透泵的方法给予AM2可以显著降低SHR的血压并改善心功能,其机制除了通过调节机体的cAMP和NO水平来发挥生理作用外,还可以通过ANP和BNP共同实现降压和心功能保护作用.     

自发性高血压大鼠肾上腺髓质素2水平的变化

背景肾上腺髓质素2(ADM2)是2004年2月由日本学者所报道的,被认为是降钙素/降钙素基因相关肽超家族的一个新肽。这与2003年11月美国斯坦福大学Dr.Roh等人发现的垂体中叶素在核苷酸和氨基酸序列上完全一致,二者被认为是同物异名。该家族的已有成员包括肾上腺髓质素、降钙素基因相关肽、降钙素和胰岛淀粉样多肽。目前研究结果表明,肾上腺髓质素2参与了心血管的调节。目的研究自发性高血压大鼠(SHR)血浆ADM2[即:垂体中叶素(IMD)]的含量和在组织中水平的升降、基因表达的变化、血浆ADM2含量与血压和心质量/体质量(HM/BM)的相互关系。方法11周龄的雄性SHR8只为实验组,同龄的雄性WistarKyoto(WKY)大鼠8只为对照组。放射免疫分析方法测定血浆和组织中ADM2的含量;RT-PCR方法测定组织中ADM2的mRNA表达;心室导管方法测定血压和心功能的变化。结果1)与WKY大鼠相比,SHR的血浆、心肌和主动脉中ADM2的含量显著增高,分别为50.0%[(317.2±25.2)vs(211.4±15.0)ng/L,P<0.01]、46.5%[(293.6±34.7)vs(200.4±21.6)ng/g,P<0.05]和32.1%[(1009.0±50.1)vs(763.8±35.0)ng/g,P<0.01];2)SHR心肌和主动脉中ADM2的mRNA水平高于WKY大鼠,分别升高76.11%[(0.75±0.33)vs(0.46±0.26)%,P<0.05]和171.1%[(1.43±0.36)%vs(0.66±0.35)%,P<0.01];3)实验组的ADM2血浆含量和收缩压呈显著负相关(r=-0.822,P<0.05)。结论ADM2作为一种心血管的活性肽,在血压调节和心肌保护过程中具有重要的意义。     

自发性高血压大鼠肾上腺髓质素2水平的变化

背景 肾上腺髓质素2(ADM2)是2004年2月由日本学者所报道的,被认为是降钙素/降钙素基因相关肽超家族的一个新肽.这与2003年11月美国斯坦福大学Dr.Roh等人发现的垂体中叶素在核苷酸和氨基酸序列上完全一致,二者被认为是同物异名.该家族的已有成员包括肾上腺髓质素、降钙素基因相关肽、降钙素和胰岛淀粉样多肽.目前研究结果表明,肾上腺髓质素2参与了心血管的调节.目的 研究自发性高血压大鼠(SHR)血浆ADM2[即:垂体中叶素(IMD)]的含量和在组织中水平的升降、基因表达的变化、血浆ADM2含量与血压和心质量/体质量(HM/BM)的相互关系.方法 11周龄的雄性SHR 8只为实验组,同龄的雄性Wistar Kyoto(WKY)大鼠8只为对照组.放射免疫分析方法测定血浆和组织中ADM2的含量;RT-PCR方法测定组织中ADM2的mRNA表达;心室导管方法测定血压和心功能的变化.结果 1)与WKY大鼠相比,SHR的血浆、心肌和主动脉中ADM2的含量显著增高,分别为50.0%[(317.2±25.2)vs(211.4±15.0)ng/L,P＜0.01]、46.5%[(293.6±34.7)vs(200.4±21.6)ng/g,P＜0.05]和32.1%[(1009.0±50.1) vs(763.8±35.0)ng/g,P＜0.01];2)SHR心肌和主动脉中ADM2的mRNA水平高于WKY大鼠,分别升高76.11%[(0.75±0.33)vs(0.46±0.26)%,P＜0.05]和171.1%[(1.43±0.36)%vs(0.66±0.35)%,P＜0.01];3)实验组的ADM2血浆含量和收缩压呈显著负相关(r=-0.822,P＜0.05).结论 ADM2作为一种心血管的活性肽,在血压调节和心肌保护过程中具有重要的意义.     

健心颗粒对慢性心力衰竭大鼠一氧化氮合酶的影响

目的 探讨健心颗粒对大鼠慢性心衰(CHF)一氧化氮合酶(NOS)的影响.方法 以32周老龄自发性高血压大鼠(SHR)的CHF模型作为研究对象,观察应用健心颗粒4周后SHR左室心肌NOS1、NOS2、NOS3蛋白表达,检测血浆血管紧张素Ⅱ(AngⅡ)、心钠素(ANP)、脑钠素(BNP)水平.结果 健心颗粒可以提高SHR的NOS1、NOS3表达,降低SHR的NOS2表达;降低血浆的AngⅡ、ANP、BNP水平.结论 健心颗粒可以通过NOS系统,调节NOS1、NOS2、NOS3三者之间的动态平衡,达到改善心功能.     

培哚普利和卡维地洛对自发性高血压大鼠Ang Ⅱ和B型利钠肽的影响

目的转换酶抑制剂(ACEI)培哚普利和β-阻滞剂(BB)卡维地洛逆转左室肥大(LVH),本文旨在探讨药物干预下自发性高血压大鼠(SHR)血管紧张素(Ang Ⅱ)和B型利钠肽(BNP)水平改变的意义.方法 15周龄雄性SHR尾动脉测压,随机分三组未治疗组(n=7)、培哚普利组(n=6)、卡维地洛组(n=7).药物溶于蒸馏水以灌胃法给予,培哚普利8 mg/kg*-1、卡维地洛4 mg/kg*-1,疗程6周,未治疗组以等量蒸馏水灌胃.15周龄雄性WKY大鼠为正常血压对照组(n=8).实验结束断头处死,取血、分离左心室.采用高效液相色谱-放射免疫(HPLC-RIA)分析技术和RIA法测定各组大鼠血浆和心肌组织Ang Ⅱ和BNP(B型利钠肽)浓度.结果 (1)经6周治疗后SHR血压和左心室/体重比值较未治疗组有显著下降(P<0.05);(2)培哚普利能显著降低心肌组织Ang Ⅱ水平(P<0.05),但能明显升高血浆Ang Ⅱ水平(P<0.05);(3)卡维地洛显著降低血浆和心肌组织Ang Ⅱ水平(P<0.05);(4)无论培哚普利、卡维地洛都能使血浆和心肌组织的BNP水平降低(P<0.05).结论培哚普利、卡维地洛逆转LVH与其降低心肌组织Ang Ⅱ相一致,BNP可看作是Ang Ⅱ的天然拮抗物,随LVH逆转而下降,BNP下降反映治疗有效.     

血浆脑钠素和心钠素对2型糖尿病舒张性心功能不鹊恼锒弦庖邋

采用固相免疫放射分析方法测定47例心脏舒张功能障碍(DHF)的2型糖尿病(DM)患者血浆脑钠素(BNP)和心钠素(ANP)浓度,并与DM心功能正常组(24例)及正常对照组(12名)进行对比分析。结果显示血浆BNP、ANP水平随着DHF程度加重而逐渐升高,而且E/A比值与BNP(r=-0.669,P<0.01)和ANP(r=-0.579,P<0.01)均呈显著负相关,提示血浆ANP、BNP是诊断2型DM心脏舒张功能不全的良好生化指标。     

充血性心力衰竭患者血浆肾上腺髓质素和心钠素的变化及临床意义

采用特异性放射免疫分析方法检测了肾上腺髓质素（ADM）和心钠素（ANP）药物治疗前后的血浆浓度。结果治疗前,CHF各组血浆ADM、ANP浓度均高于对照组（P〈0．05）。治疗后心功能Ⅱ,Ⅲ级组ADM血浆含量明显低于治疗前（P〈0．05）,Ⅳ级组血浆ADM无明显变化;心功能Ⅲ级和Ⅳ级组ANP血浆浓度明显低于治疗前,心功能Ⅱ组血浆ANP无明显变化。认为ADM和ANP可能通过不同的信号传导通路,共同参与心衰病理生理的调节过程。     

脑钠素等在慢性呼吸衰竭并肺心病患者中临床应用价值的探讨

脑钠素(BNP,美国Peninsula laboratories公司)为钠肽类家族一个新成员[1],在人体循环中的脑钠素主要从心室的心肌组织产生,在充血性心力衰竭、急性心梗血浆BNP水平升高已有报道,但BNP在肺循环的作用尚不完全了解,而心钠素(ANP,北京北方生物技术研究所)具有调节肺循环血管张力,与肺动脉高压病理生理形成有关.我们通过测定慢性阻塞性肺疾病(COPD)慢性呼吸衰竭(CRF)并肺心病(PHD)患者血浆BNP和ANP水平,探讨其临床价值.     

精芪燕面方对自发高血压大鼠血压升高及心肌损伤的干预研究

目的探讨精芪燕面方(JQYM)对自发性高血压大鼠(SHR)血压升高及心肌损伤的干预效果,为药食同源的中药组方防治高血压的临床应用提供理论和实验依据。方法采用SHR雄性大鼠作为高血压动物模型,分为SHR模型组、JQYM组、坎地沙坦酯片组(Can组),以同周龄同源Wistar-Kyoto(WKY)雄性大鼠为正常对照组,每组各12只。各组大鼠从6周龄起开始治疗干预14周,于20周龄分析血压、旋转耐受时间、心脏组织病理改变及肿瘤坏死因子-α(TNF-α)、钠尿肽(ANP)基因的mRNA表达水平。结果与正常对照组比较,SHR模型组收缩压及舒张压随着周龄变化显著升高;与SHR模型组比较,JQYM组SHR大鼠收缩压及舒张压水平显著降低(P 0.05)。与SHR模型组比较,JQYM组旋转耐受时间显著延长(P 0.05)。与SHR模型组比较,JQYM组及Can组心肌损伤程度显著减轻(P 0.05)。与SHR模型组比较,Can组及JQYM组心肌细胞横截面面积缩小,且JQYM组优于Can组(P 0.05)。与SHR模型组比较,Can组及JQYM组TNF-α及ANP mRNA表达水平显著降低,且JQYM组较Can组降低明显(P0.05)。结论 JQYM干预能够显著降低SHR大鼠收缩压及舒张压水平,延长旋转耐受时间,减轻高血压相关心肌损伤及心肌细胞肥大样改变,降低心脏组织中TNF-α及ANP mRNA的表达水平。JQYM具有显著的抗SHR大鼠血压升高的效应,同时对高血压相关心肌损伤及心肌细胞肥大等病理改变具有显著的干预效应。     

培哚普利和卡维地洛对自发性高血压大鼠AngⅡ和B型利钠肽的影响

目的　转换酶抑制剂 (ACEI)培哚普利和β -阻滞剂 (BB)卡维地洛逆转左室肥大 (LVH) ,本文旨在探讨药物干预下自发性高血压大鼠 (SHR)血管紧张素 (AngⅡ )和B型利钠肽 (BNP)水平改变的意义。 方法　 15周龄雄性SHR尾动脉测压 ,随机分三组 :未治疗组 (n =7)、培哚普利组 (n =6 )、卡维地洛组 (n =7)。药物溶于蒸馏水以灌胃法给予 ,培哚普利 8mg/kg·-1、卡维地洛 4mg/kg·-1,疗程 6周 ,未治疗组以等量蒸馏水灌胃。 15周龄雄性WKY大鼠为正常血压对照组 (n =8)。实验结束断头处死 ,取血、分离左心室。采用高效液相色谱 -放射免疫 (HPLC RIA)分析技术和RIA法测定各组大鼠血浆和心肌组织AngⅡ和BNP(B型利钠肽 )浓度。 结果　 (1)经 6周治疗后SHR血压和左心室/体重比值较未治疗组有显著下降 (P <0 0 5 ) ;(2 )培哚普利能显著降低心肌组织AngⅡ水平 (P <0 0 5 ) ,但能明显升高血浆AngⅡ水平 (P <0 0 5 ) ;(3)卡维地洛显著降低血浆和心肌组织AngⅡ水平 (P <0 0 5 ) ;(4)无论培哚普利、卡维地洛都能使血浆和心肌组织的BNP水平降低 (P <0 0 5 )。结论　培哚普利、卡维地洛逆转LVH与其降低心肌组织AngⅡ相一致 ,BNP可看作是AngⅡ的天然拮抗物 ,随LVH逆转而下降 ,BNP下降反映治疗有效。     

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.