缬沙坦治疗对自发性高血压大鼠心肌纤维化的影响

目的观察缬沙坦对自发性高血压大鼠(SHR)心肌纤维化的影响.方法 30只12周龄雄性SHR大鼠,随机分成3组(1)大剂量缬沙坦组(n=10 缬沙坦30 mg/kg*d);(2)小剂量缬沙坦组(n=10 缬沙坦10 mg/kg*d); (3)SHR空白对照组(n=10);(4) 同龄雄性正常血压WKY 大鼠对照组(n=10).给药4周; 天狼星红染色法使胶原特殊染色,计算机图象分析测量心肌切片的胶原容积分数和心肌小动脉周围胶原面积与小动脉面积比表示心肌纤维化程度.结果与SHR组相比大小剂量缬沙坦组,均能有效降低SHR血压(P<0.05).并能改善SHR大鼠左心室肥厚(P<0.05)并使心室内、外膜及心肌小动脉周围的胶原减少,其中大剂量组各指标均较SHR有显著差异(P<0.05).结论缬沙坦对SHR大鼠的心肌纤维有显著的抑制作用.     

辛伐他汀对SHR心肌组织SOD、MDA、NOS、NO及心肌间质胶原含量的影响

目的　观察辛伐他汀对自发性高血压大鼠 (SHR)心肌纤维化的影响。方法 2 0只 16周龄雄性SHR大鼠 ,随机分成 2组 :( 1)辛伐他汀组 (n =10辛伐他汀 2mg/kg·d) ;( 2 )SHR空白对照组 (n =10 ) ;( 3)同龄雄性正常血压WKY大鼠对照组 (n =10 )。给药 12周后称量大鼠左室重量并计算大鼠左室重量指数 ;测定心肌组织丙二醛、超氧歧化酶、一氧化氮及一氧化氮合酶 ;用改良VG染色法使胶原特殊染色 ,计算机图像分析测量心肌间质及心肌小动脉周围胶原的胶原容积分数对心肌纤维化程度进行比较。结果辛伐他汀组与SHR组相比心肌超氧歧化酶无明显改变、丙二醛明显减少而心肌一氧化氮及结构型一氧化氮合酶 (cNOS)活性明显升高 ;辛伐他汀组均未能有效降低SHR血压和左心室肥厚 (P <0 0 5 )但能使心室内、外膜及心肌小动脉周围的胶原减少。结论一氧化氮 /活性氧平衡失调可能是导致高血压心肌纤维化的又一个重要因素 ;辛伐他汀抗纤维化作用可能与其抗氧化作用及改善心肌cNOS活性密切相关     

辛伐他汀对SHR心肌组织SOD、MDA、NOS、NO及心肌间质胶原含量的影响

目的观察辛伐他汀对自发性高血压大鼠(SHR)心肌纤维化的影响.方法 20只16周龄雄性SHR大鼠,随机分成2组(1)辛伐他汀组(n=10辛伐他汀2 mg/kg*d);(2)SHR空白对照组(n=10);(3)同龄雄性正常血压WKY大鼠对照组(n=10).给药12周后称量大鼠左室重量并计算大鼠左室重量指数;测定心肌组织丙二醛、超氧歧化酶、一氧化氮及一氧化氮合酶;用改良VG染色法使胶原特殊染色,计算机图像分析测量心肌间质及心肌小动脉周围胶原的胶原容积分数对心肌纤维化程度进行比较.结果辛伐他汀组与SHR组相比心肌超氧歧化酶无明显改变、丙二醛明显减少而心肌一氧化氮及结构型一氧化氮合酶(cNOS)活性明显升高;辛伐他汀组均未能有效降低SHR血压和左心室肥厚(P<0.05)但能使心室内、外膜及心肌小动脉周围的胶原减少.结论一氧化氮/活性氧平衡失调可能是导致高血压心肌纤维化的又一个重要因素;辛伐他汀抗纤维化作用可能与其抗氧化作用及改善心肌cNOS活性密切相关.     

通心络治疗对自发性高血压大鼠心肌纤维化的影响

目的：观察通心络对自发性高血压大鼠(SHR)心肌纤维化的影响。方法：30只12周龄雄性SHR大鼠，随机分成大剂量通心络组、小剂量通心络组、SHR空白对照组3组，每组10只；另取10只同龄雄性正常血压WKY大鼠作为对照组。给药12周，天狼星红染色法使肢原特殊染色，计算机图像分析测量心肌切片的肢原容积分数和心肌小动脉周围肢原面积与小动脉面积比表示心肌纤维化程度；放免法(RIA)测定血浆AngⅡ的浓度：结果：与SHR组相比，大、小剂量通心络组均能在一定程度上抑制S服血压升高(P＜0．05)。通心络大、小剂量组治疗均能在一定程度上改善SHR大鼠左心室肥厚(P＜0．05)，并使心室内、外膜及心肌小动脉周围的胶原减少，同时血浆AngⅡ浓度较SHR组下降，其中大剂量组各指标均较SHR有统计学意义(P＜0．05)。结论：通心络对SHR大鼠的心肌纤维化有显著的抑制作用。     

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     

氯沙坦或卡托普利对自发性高血压大鼠心脏纤维化的干预研究

目的　探讨在不同水平阻断肾素 -血管紧张素系统 (RAS)对高血压心肌纤维化的影响。方法　 2 9只自发性高血压大鼠 (SHR)随机分成 (1)SHR对照组 (n =15 ) ;(2 )氯沙坦组 (n =7,30mg·kg-1·d-1) ;(3)卡托普利组 (n =7,10 0mg·kg-1·d-1) ;(4)WKY(n =12 )为非高血压组。治疗组每日灌胃给药 ,对照组蒸馏水灌胃 15周后 ,获取标本。结果　 1.SHR心肌血管紧张素Ⅱ (AngⅡ )和醛固酮 (Ald)浓度、羟脯氨酸和Ⅰ /Ⅲ型胶原比值较同龄WKY大鼠明显增高 (P <0 0 1) ,而心肌胶原单体 /二聚体 (α/ β)比值和基质金属蛋白酶 - 1(MMPs- 1)活力降低 (P <0 0 1) ,且随病程而进一步升高或降低。 2 .经氯沙坦或卡托普利干预后 ,心肌AngⅡ、Ald浓度、心肌羟脯氨酸和Ⅰ、Ⅲ型胶原比值有不同程度的降低 (P <0 0 1) ,而心肌胶原单体 /二聚体 (α/ β)比值和MMPs- 1活性升高 (P <0 0 1) ,逆转了心肌纤维化。3.氯沙坦在改善胶原表型、胶原可溶性及提高MMPs- 1活性优于卡托普利。结论　不同水平阻断肾素血管紧张素系统对纤维化逆转不仅减少胶原含量 ,还改善表型和交联的异常     

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.     

食盐对高血压大鼠及正常血压大鼠心肌纤维化的影响

目的:观察食盐对自发性高血压大鼠(SHR)及正常血压大鼠(WKY)心肌纤维化的影响,并探讨其可能机制。方法:SHR和WKY各20只分别分为两组:①高盐饮食组(SHRSL,n=10和WKYSL,n=10)饮用含2％NaCl溶液;②正常盐饮食组(SHRNS,n=10和WKYNS,n=10)饮用不含NaCl清水,共饲养6周。VG染色和图像处理观察心肌纤维化情况,放免测定心肌局部内皮素-1(ET-1)含量。结果:①SHRSL组心肌间质胶原百分比(CVF)及血管周围胶原面积与血管腔面积百分比(PVCA)显著高于SHRNS(P<0.01),WKYSL组的CVF、PVCA明显高于WKYNs组(P<0.05);②SHRSL组心肌局部ET-1含量显著高于SHRNS组(P<0.01),WKYSL组与WKYNS组心肌局部ET-1含量无差别(P>0.05)。结论:高盐饮食可引起SHR及WKY心肌纤维化,盐负荷后SHR心肌局部ET-1含量的增加可能是SHR心肌纤维化加重的原因之一。     

依那普利或氯沙坦对SHR左室肥厚和心肌纤维化的影响

目的:观察自发性高血压大鼠(SHR)左室肥厚和心肌纤维化各指标的改变,以及依那普利和氯沙坦的保护作用.方法:雄性SHR(n=30)自第10周始服用依那普利(20mg@kg-1@d-1),或氯沙坦(25mg@kg-1@d-1),或二者合用(依那普利10mg@kg-1@d-1,氯沙坦12.5mg@kg-1@d-1)至第16周,并以年龄、性别、数量配对的未治疗SHR和Wistar-kyoto(WKY)大鼠作对照.测定收缩压(SBP)、左室重量(LVM)以及左室重量指数(LVMI)和左室心肌胶原含量;计算机图象分析心肌细胞大小、心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA).结果:SHR的SBP、LVM、LVMI、心肌胶原含量、心肌细胞的横截面积、CVF和PVCA均显著高于WKY对照组(P＜0.001).SHR治疗组上述指标显著低于SHR未治疗组(P＜0.01),依那普利与氯沙坦之间无显著差别(P＜0.05).二者合用比单用依那普利或氯沙坦更有效(P＜0.05).结论:依那普利和氯沙坦可显著的降低血压、逆转SHR早期左室肥厚和心肌纤维化,而且二者合用在逆转左室肥厚和心肌纤维化方面效果更明显.     

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.