缬沙坦和螺内酯对自发性高血压大鼠心肌整和素β1 的作用

目的比较自发性高血压大鼠(SHR)和WKY心肌整和素β1 的表达以及缬沙坦和螺内酯对SHR整和素β1的影响.方法将18只6周龄SHR随机分成3组,每组6只.其中2组分别灌喂缬沙坦20 mg*kg-1*d-1,和螺内酯10 mg*kg-1*d-1,另一对照组给正常饮水,并与雄性同周龄WKY6只比较.实验期14周,免疫组化法检测四组大鼠心肌整和素β1的表达.结果 SHR对照组心肌整和素β1表达明显高于WKY组,和SHR对照组比较缬沙坦组整和素β1的表达下降(P<0.05),而螺内酯组整和素β1 的表达无显著改变;两治疗组血压、LVM/BW以及心肌纤维化程度均显著低于SHR组(P<0.05),而且两治疗组间比较缬沙坦组血压和心肌纤维化程度降低更明显(P<0.05).结论缬沙坦除降低血压外,还能抑制整和素β1表达,而螺内酯对整和素β1 的表达无明显抑制作用;而缬沙坦对心肌纤维化的抑制作用优于螺内酯.提示整和素β1在高血压心肌纤维化进程中起了一定作用.     

缬沙坦对自发性高血压大鼠整合素β1和纤维黏连蛋白表达的影响

目的研究缬沙坦对自发性高血压大鼠(SHR)左室心肌整合素β1和纤维黏连蛋白(FN)表达的影响,探讨高血压心肌纤维化的机制.方法选用6周龄的雄性SHR 12只,随机均分为2组SHR阳性对照组;缬沙坦干预组(SHR-V),灌喂缬沙坦20 mg*kg-1*d-1.另选同源正常血压的WKY大鼠6只为正常对照组.实验期14周.观察血压、左室重量/体重(LVW/BW)、胶原容积分数,并用免疫组化法检测3组大鼠心肌整合素β1和FN的表达.结果缬沙坦可显著降低SHR的血压、LVW/BW及左室心肌的胶原含量,此外SHR阳性对照组整合素β1 和FN 的表达明显高于正常对照组(P<0.05),而SHR-V组两者的表达显著低于SHR阳性对照组(P<0.05).结论缬沙坦除可降低血压外,还能显著抑制整合素β1 和FN的表达,抑制甚至逆转心肌纤维化过程.     

缬沙坦和螺内酯对自发性高血压大鼠心肌整和素β1的作用

目的　比较自发性高血压大鼠 (SHR)和WKY心肌整和素β1的表达以及缬沙坦和螺内酯对SHR整和素 β1的影响。方法　将 18只 6周龄SHR随机分成 3组 ,每组 6只。其中 2组分别灌喂缬沙坦 2 0mg·kg- 1·d- 1,和螺内酯 10mg·kg- 1·d- 1,另一对照组给正常饮水 ,并与雄性同周龄WKY6只比较。实验期 14周 ,免疫组化法检测四组大鼠心肌整和素 β1的表达。结果　SHR对照组心肌整和素 β1表达明显高于WKY组 ,和SHR对照组比较缬沙坦组整和素 β1的表达下降 (P <0 0 5) ,而螺内酯组整和素 β1的表达无显著改变 ;两治疗组血压、LVM/BW以及心肌纤维化程度均显著低于SHR组 (P <0 0 5) ,而且两治疗组间比较缬沙坦组血压和心肌纤维化程度降低更明显 (P <0 0 5)。结论　缬沙坦除降低血压外 ,还能抑制整和素 β1表达 ,而螺内酯对整和素β1的表达无明显抑制作用 ;而缬沙坦对心肌纤维化的抑制作用优于螺内酯。提示整和素 β1在高血压心肌纤维化进程中起了一定作用     

口服小剂量螺内酯抗高血压大鼠心肌纤维化

目的观察口服小剂量螺内酯对自发性高血压大鼠(SHR)血压、心肌间质和血管周围胶原沉积的干预,探讨螺内酯在高血压心肌纤维化进展期对心脏的保护作用。方法20只雄性SHR随机分为螺内酯组(10只)和安慰剂组(10只),另设Wistar-kyoto鼠7只(WKY组)。Western blot方法分析Ⅰ型胶原的表达;天狼猩红-苦味酸染色观察心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果与安慰剂组比较,螺内酯组Ⅰ型胶原含量、CVF、PVCA显著降低(P<0.01),收缩压、舒张压、平均动脉血压、血K+、心脏重量指数、左心室重量指数、心率未见明显差异。结论口服小剂量螺内酯通过减少Ⅰ型胶原的沉积,起到抗高血压大鼠心肌纤维化的作用。     

缬沙坦和螺内酯对自发性高血压大鼠心肌胰岛素样生长因子-1的影响

目的观察自发性高血压大鼠(SHR)和WKY大鼠心肌胰岛素样生长因子-1(IGF-1)及其受体(IGF-1R)的表达和缬沙坦与螺内酯对SHR的IGF-1的影响,探讨IGF-1与心肌肥厚的病理机制.方法将18只6周龄SHR随机分成3组,每组6只.其中2组分别灌喂缬沙坦30 mg/kg·d和螺内酯20 mg/kg·d,另一对照组给正常饮水,并与雄性同周龄WKY 6只比较.实验期14周,免疫组化法检测四组大鼠心肌IGF-1及IGF-1R的表达.结果两治疗组血压、LVM/BW均显著低于SHR组(P＜0.01).SHR对照组IGF-1和IGF-1R的表达明显高于WKY组(IGF-1180.4±12.3比97.6±10.1;IGF-1R203.3±14.4比92.4±10.3;P＜0.01),缬沙坦组和螺内酯组的IGF-1和IGF-1R均比SHR对照组下降(IGF-1122.2±14.8比139.8±7.9比180.4±12.3;IGF-1R130.9±11.7比149.9±8.9比203.3±14.4;P＜0.01).而且缬沙坦比螺内酯的作用更为明显(P＜0.05).结论IGF-1及IGF-1R在肥厚心肌中表达明显增加,而缬沙坦和螺内酯在降压的同时可以抑制IGF-1及IGF-1R的表达,结果提示IGF-1和IGf-1R在心肌肥厚发展中起一定作用.     

缬沙坦和螺内酯对高血压大鼠心肌生长因子和Ⅰ型胶原mRNA表达的影响

目的　观察血管紧张素Ⅱ (AngⅡ )AT1 受体拮抗剂缬沙坦和盐皮质激素受体拮抗剂螺内酯对自发性高血压大鼠 (SHR)左心室生长因子和Ⅰ型胶原mRNA表达的影响。方法　将 1 8只雄性SHR随机分为三组 :SHR对照组、缬沙坦治疗组、螺内酯治疗组 ,每组 6只。其中两治疗组分别用缬沙坦 30mg·kg- 1 ·d- 1 、螺内酯 2 0mg·kg- 1 ·d- 1 溶于饮水灌胃 ,每天一次 ,连续治疗 1 3周 ;另一组给正常饮水。另选同源同系Wistar kyoto大鼠 6只作为正常对照组。用RT PCR方法检测大鼠心肌转化生长因子 β1 (TGFβ1 )、肝细胞生长因子 (HGF)、Ⅰ型胶原mRNA水平。结果　治疗1 3周后 ,缬沙坦组和螺内酯组TGFβ1 、Ⅰ型胶原mRNA水平明显低于SHR对照组 (P <0 0 1 ) ,但高于WKY组 (P <0 0 1 ) ,其中螺内酯组Ⅰ型胶原mRNA水平高于缬沙坦组 (P <0 0 1 ) ;缬沙坦组和螺内酯组的HGFmRNA水平高于SHR对照组 (P <0 0 1 ) ,但低于WKY组 (P均 <0 0 1 ) ,螺内酯组的HGFmRNA水平低于缬沙坦组 (P <0 0 1 )。结论AngⅡAT1 受体拮抗剂缬沙坦和盐皮质激素受体拮抗剂螺内酯均能抑制SHR的左室肥厚和心肌纤维化     

缬沙坦和螺内酯对高血压大鼠心肌生长因子和Ⅰ型胶原mRNA表达的影响

目的观察血管紧张素Ⅱ(Ang Ⅱ)AT1受体拮抗剂缬沙坦和盐皮质激素受体拮抗剂螺内酯对自发性高血压大鼠(SHR)左心室生长因子和Ⅰ型胶原mRNA表达的影响.方法将18只雄性SHR随机分为三组SHR对照组、缬沙坦治疗组、螺内酯治疗组,每组6只.其中两治疗组分别用缬沙坦30 mg*kg-1*d-1、螺内酯20 mg*kg-1*d-1溶于饮水灌胃,每天一次,连续治疗13周;另一组给正常饮水.另选同源同系Wistar-kyoto大鼠6只作为正常对照组.用RT-PCR方法检测大鼠心肌转化生长因子β1(TGF β1)、肝细胞生长因子(HGF)、Ⅰ型胶原mRNA水平.结果治疗13周后, 缬沙坦组和螺内酯组TGFβ1、Ⅰ型胶原mRNA水平明显低于SHR对照组(P<0.01),但高于WKY组(P<0.01),其中螺内酯组Ⅰ型胶原mRNA水平高于缬沙坦组(P<0.01);缬沙坦组和螺内酯组的HGF mRNA水平高于SHR对照组(P<0.01),但低于WKY组(P均<0.01),螺内酯组的HGF mRNA水平低于缬沙坦组(P<0.01).结论AngⅡ AT1受体拮抗剂缬沙坦和盐皮质激素受体拮抗剂螺内酯均能抑制SHR的左室肥厚和心肌纤维化.     

厄贝沙坦对SHR左心室肥厚和心肌纤维化的影响

目的 探讨厄贝沙坦对自发性高血压大鼠(SHR)左心室肥厚(LVH)和心肌纤维化的影响。方法 16只16周龄雄性SHR,随机分为厄贝沙坦治疗组和SHR空白对照组;另设同源的WKY大鼠8只为正常对照组。治疗组予厄贝沙坦15 mg/（kg·d）灌胃给药,8周后处死动物,测量左心室心肌厚度并称质量,计算左心室质量/体质量比(LVM/BM);通过Van Gieson染色法观察左心室心肌胶原变化,对左心室心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)进行定性和半定量分析;HE染色光镜观察左心室心肌病理变化。结果 与WKY组相比,SHR对照组的尾动脉收缩压(SBP)、LVM/BM、左心室壁厚度、CVF、PVCA、均显著增高(P<0.01);与SHR对照组相比,厄贝沙坦治疗组能有效降低SHR的SBP,改善LVH(P<0.01),减少心肌间质及心肌小动脉周围的胶原(P<0.01)。结论 厄贝沙坦可有效降低SHR血压,减轻心肌纤维化和LVH。     

小剂量贝那普利联合螺内酯对自发性高血压大鼠心肌纤维化的干预作用及超声背向散射积分评价

目的观察小剂量贝那普利联合螺内酯对自发性高血压大鼠(SHR)左室心肌纤维化的影响,并应用超声背向散射积分(IBS)进行评价。方法21只雄性SHR随机分成模型对照组(SHR组)、贝那普利干预组[SHR-B组,贝那普利10mg/(kg·d)灌胃]及小剂量贝那普利联合螺内酯干预组[SHR-BS组,贝那普利5mg/(kg.d)+螺内酯10mg/(kg·d)灌胃],另外选择同周龄雄性Wistar大鼠设为正常对照组(WKY组),SHR组及WKY组蒸馏水灌胃2mL/d。12周后超声测量IBS参数[峰-峰强度(PPI);平均图像强度(AII)];对心肌组织进行羟脯氨酸含量(HPC)测定,Masson染色计算胶原容积分数(CVF)、血管周围胶原面积(PVCA)、冠状小动脉管壁厚/管外径比值(T/D),嗜银染色计算嗜银纤维容积分数(APFVF),对结缔组织生长因子(CTGF)蛋白表达的半定量分析进行免疫组织化学染色。结果与WKY组比较,SHR组的超声AII%明显增高,PPI减低,SHR组的纤维化指标(HPC、CVF、PVCA、T/D、APFVF、CTGF的表达)增高。干预后,与SHR组比较AII%减低,PPI增高,纤维化指标减轻...     

依那普利对自发性高血压大鼠心脏局部血管紧张素转换酶及左室肥厚的作用

目的　研究自发性高血压大鼠 (SHR)心脏局部血管紧张素转换酶 (ACE)活性对左室肥厚的影响及依那普利的作用。方法　选用 1 2w龄SHR 40只 ,随机分为两组 ,一组给予依那普利 30mg/ (kg·d)治疗 ,另一组作为对照 ,同时设一同周龄的WKY作为正常对照 ,用病理学图像分析法检测SHR左心室壁厚度、心肌细胞体积比例 (CVF)和心肌血管周围胶原面积和管腔面积比例 (PVCA) ,放免法测定血管紧张素Ⅱ (AngⅡ )浓度 ,荧光法测定ACE活性。结果　 (1 )SHR治疗组 (SHR T)BW/LV与正常对照组 (WKY C)相比无差异 (P >0 0 5) ;(2 )SHR C组AngⅡ浓度为 (5 780± 3 734)ng/mg组织 ,显著高于WKY C组〔(2 72 3± 0 84)ng/mg组织〕(P <0 0 5) ;而依那普利治疗后SHR T组AngⅡ浓度为 (2 757± 2 71 7)ng/mg组织 ,与WKY C组相比无显著差异。 (3)SHR T、SHR C、WKY C三组ACE活性分别为 (0 47± 0 1 2 )单位 / (ml·mg组织 ) ,(0 60± 0 1 3)单位 / (ml·mg组织 ) ,(0 45± 0 1 9)单位 / (ml·mg组织 ) ,SHR T组与SHR C组比较有显著差异 (P <0 0 1 ) ,SHR T组与WKY C组比较无显著差异 (P >0 0 5)。 (4)SHR T组CVF和PVCA分别为 (1 98± 1 57) %和 (0 68± 0 1 9) % ,显著低于SHR C组〔(5 1 1± 2 2 5) % ,(1 2 0± 0     

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.