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.     

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500ng/(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(±LVdp/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。     

自发性高血压大鼠心血管组织中肾上腺髓质素2受体系统的变化

目的:探讨自发性高血压大鼠(SHR)心血管组织中肾上腺髓质素2(ADM2)及其受体系统的基因表达和蛋白水平变化,以及与ADM2血浆水平的相互关系.方法:8只11周龄的雄性SHR(SHR组),8只同龄的雄性Wistar Kyoto大鼠(WKY组).半定量RT-PCR方法测定大鼠心血管组织中ADM2及其受体系统降钙素受体样受体(CRLR)和受体活性修饰蛋白(RAMPs)mRNA水平;Western blot法测定心血管组织中CRLR和RAMPs的蛋白含量;放射免疫法测定血浆中ADM2含量.结果:①SHR心肌中ADM2、CRLR、RAMP1、RAMP2和RAMP3的mRNA水平较WKY组分别高76.1%、41.6%、69.2%、48.3%和109.1%(均P＜0.05);主动脉中分别高171.11%(P＜0.01)、69.9%(P＜0.05)、100.09%(P＜0.01)、131.8 0%和69.7%(均P＜0.05).②SHR心肌中CRLR、RAMP1和RAMP3的蛋白水平较WKY组分别高136.0%、60.3%、63.9%(均P＜0.05),而RAMP2则显著增高292.5%(P＜0.01);SHR主动脉中CRLR、RAMP1、RAMP2和RAMP3的蛋白水平较WKY组分别高112.4%、92.3%、41.1%和67.7%(均P＜0.01).③SHR的ADM2血浆含量和受体的蛋白水平-CRLR、RAMP1、RAMP2在主动脉中的含量呈显著正相关(r=0.883 8,0.929 9,0.888 1,均P＜0.05).结论:ADM2及其受体系统在原发性高血压的发生发展过程中可能具有重要的病理生理意义.     

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.     

ACE2和ACE在自发性高血压大鼠心肌中的变化

目的:观察自发性高血压大鼠(SHR)心肌的血管紧张素转化酶(ACE)和ACE2的表达,以探讨ACE2和ACE在高血压发生发展中的变化。方法:取15只SHR,处死,分离左心室,行RT-PCR、Western blot蛋白质免疫印迹和免疫组织化学检测ACE及ACE2表达;同步取10只WKY大鼠作为正常血压对照组。结果:SHR组心肌ACE的mRNA和蛋白质表达都显著高于WKY组[(1.68±0.34)∶(0.33±0.12),P<0.05;(1.21±0.14)∶(0.71±0.11),P<0.05],而ACE2的mRNA和蛋白质表达皆明显低于WKY组[(0.50±0.15)∶(1.16±0.24),P<0.05;(0.71±0.24)∶(1.22±0.14),P<0.05)]。免疫组织化学染色显示,SHR组ACE的阳性率明显高于WKY组(87%∶50%,P<0.05),而ACE2的阳性率明显低于WKY组(27%∶70%,P<0.05)。结论:SHR心肌ACE明显升高,ACE2显著降低;SHR高血压发生发展过程中存在着ACE和ACE2表达的失衡。     

氯沙坦对自发性高血压大鼠心脏血管紧张素转换酶2-血管紧张素(1～7)-MAS-ERK通路的影响

目的探讨氯沙坦对自发性高血压大鼠(SHR)心肌中血管紧张素转换酶2(ACE2)-血管紧张素(1～7)[Ang(1-7)]-MAS-ERK通路的影响。方法30周龄SHR随机分为SHR组(n=11)、氯沙坦组[氯沙坦灌胃30mg/(kg·d),n=12],以Wistar大鼠(WKY)作正常对照(n=12)。处理12周后,应用放射免疫法检测大鼠血浆及心肌组织血管紧张素Ⅱ(AngⅡ)、血管紧张素(1～7)[Ang-(1-7)]水平;采用RT-PCR法检测各组大鼠心肌血管紧张素转换酶(ACE)、ACE2和MAS受体mRNA水平;采用Western blot法检测ACE、ACE2和磷酸化细胞外信号调节激酶(pERK1/2)蛋白表达水平。结果用药12周后,氯沙坦组血压明显低于SHR组[(164.3±21.6)比(241.3±24.5)mmHg,P<0.01];SHR组心肌ACE mRNA和蛋白表达水平显著高于WKY组,而ACE2 mRNA和蛋白表达、心肌MAS受体mRNA表达水平明显低于WKY组,差异有统计学意义(P<0.01);氯沙坦组ACE2 mRNA和蛋白表达、MAS mRNA表达水平高于SHR组(P<0.01),心...     

运动对高血压大鼠血浆尾加压素Ⅱ及前列腺素I2的影响

目的:研究运动对自发性高血压大鼠(SHR)血浆尾加压素Ⅱ(UⅡ)的影响。方法:雄性SHR16只,随机分为两组,即安静对照组(8只)和运动组(8只),另正常雄性Wistar大鼠(8只)作为正常对照组。SHR运动组进行8周游泳运动训练。8周后,分别测定3组鼠血浆UⅡ、前列腺素Ⅱ(PGI2)含量。结果:SHR游泳组大鼠血浆UⅡ含量较正常对照组显著性增加[(1.17±0.17)ng/ml∶(1.09±9.77)ng/ml,P0.05],SHR游泳组血压较SHR对照组显著下降[(157.6±7.06)mmHg∶(185.9±6.64)mmHg,P0.01],血浆PGI2含量较SHR对照组患者增加[(183.25±43.46)pg/ml∶(135.43±22.13)pg/ml,P0.01]。结论:适度运动能提高SHR血浆VⅡ、PGI含量,从而使舒血管物质增多,血压下降。     

缬沙坦和螺内酯联合治疗对血浆肾上腺髓质素和醛固酮的影响

目的 研究缬沙坦、螺内酯以及两者联用逆转自发性高血压大鼠(SHRs)心肌肥厚中血浆肾上腺髓质素(ADM)和醛固酮(Ald)的变化.方法 12周龄SHRs 32只,随机分成4组,即对照组、缬沙坦组、螺内酯组、两者联用组,每组各8只,另设WKY大鼠(8只,周龄及体重同SHRs)为正常对照组.尾套法测血压,1次/周,4月后处死大鼠,测定左心室质量指数(LVMI)、心肌胶原含量(MCC)及心肌胶原容积分数(CVF).放免法测血浆ADM和Ald水平.结果 与SHR对照组血压(200±20)mm Hg比较,螺内酯组(159±20)mm Hg,缬沙坦组( 140±20)mm Hg,联用组( 132±20)mm Hg;各用药组经12周治疗后LVMI、MCC、CVF均有明显降低(P均<0.05～0.01).缬沙坦组血浆Ald水平稍降低[(350.5±34.8)pg/mL,P＞0.05]出现Ald逃逸现象,螺内酯组下降明显[(310.6±30.6 )pg/mL,P＜0.05],联用组能更明显地降低血浆Ald[(260.4±60.1 )pg/mL,P＜0.05].血浆ADM水平在各组均有不同程度的下降,但仍然显著高于WKY组(P＜0.05或P＜0.01).结论 (1)在SHRs中长期应用AT-1受体拮抗剂可引起血浆Ald逃逸;(2)缬沙坦和螺内酯联合应用逆转高血压左心室肥厚.因为其降低血Ald水平,因此优于单用缬沙坦.(3)ADM作为一个抗重塑的自分泌和(或)旁分泌因子,在左室肥厚消退的情况后有所降低,但仍处于一种较高水平;     

自发性高血压大鼠肾上腺髓质素含量与中性内肽酶分布的关系

目的测定自发性高血压大鼠(SHR) 与WKY大鼠组织肾上腺髓质素(ADM)含量和中性内肽酶(NEP)活性及其表达水平,以探讨NEP的变化在高血压时组织ADM水平升高中的意义.方法采用放射免疫分析方法和荧光分光光度法分别检测血浆和组织的ADM含量和NEP的活性,同时用半定量RT-PCR和免疫组织化学染色法分别检测组织NEP mRNA和NEP蛋白的表达和分布.结果 ADM和NEP广泛分布于大鼠的血浆和组织,SHR的ADM含量在各组织普遍高于WKY大鼠.SHR心脏和小肠NEP的活性和mRNA表达均显著低于WKY大鼠,ADM含量与NEP活性呈负相关.反之,SHR血浆和肾脏NEP活性、肾脏NEP mRNA水平与蛋白量均高于WKY大鼠,ADM含量与NEP活性呈正相关.在肺脏和主动脉,NEP的活性无明显变化.结论 NEP在自发性高血压大鼠各组织器官中的变化与ADM含量的变化不一致,提示高血压时组织局部的NEP对ADM含量的影响不同.     

犬尿氨酸氨基转移酶和犬尿喹啉酸在自发性高血压大鼠中的变化

目的犬尿氨酸氨基转移酶(KAT)催化犬尿氨酸(KYN)生成犬尿喹啉酸(KYNA)。研究表明中枢KAT 及 KYNA 可能参与血压调节,但外周 KAT 变化及 KYNA 生成与血压的关系尚无报道。检测肾脏 KATⅡ基因表达,KAT 活性,及尿 KYNA 含量在自发性高血压大鼠(SHR)和 WKY 大鼠(正常对照组)的变化。方法采用实时定量 PCR 技术检测 KATⅡ基因表达,高效液相色谱(HPLC)检测尿 KYNA 及 KAT 活性(通过测定其酶促反应产物 KYNA)。结果虽然肾皮质和肾髓质 KATⅡ基因 mRNA 表达在 SHR 与 WKY 之间差异无统计学意义(P>0.05);但 SHR 肾皮质 KAT 的活性显著低于 WKY[(0.563±0.037)vs(1.037±0.131)μmol/(g·min),P=0.017]。同时发现 SHR 组尿 KYNA 含量在显著低于 WKY 组[(7.8±1.8)vs(19.9±3.5)μmol/24 h,P=0.013]。相关分析显示,肾皮质 KAT 的活性(r=-0.418,P=0.023)和尿 KYNA 含量(r=-0.723,P=0.001)与血压都呈显著负...     

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.     

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.     

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.