血压平逆转肾性高血压大鼠左室重构的作用及机制

目的　探讨复方中药制剂血压平逆转二肾一夹 (2K1C)肾性高血压大鼠左室重构的作用及机制。方法　采用 2K1C法 ,建立肾性高血压大鼠 (RHR)模型 ,术后 8周将造模成功的 40只RHR随机分为 5组 ,每组 8只 ,采用放免法检测血清Ⅲ型前胶原(PCⅢ ) ,测量心肌细胞面积、周长、平均直径、长径和短径。SP免疫组化测量原癌基因C -myc和C -fos表达阳性细胞的平均光密度值。结果　①血压平有降低血压、左室重量 (LVW )、左室重量指数 (LVW /BW )、心肌细胞体积的作用 ;②血压平可降低血清PCⅢ含量 ,抑制原癌基因C -myc和C -fos的表达 ;③血压平的降压和逆转左室重构的药理作用有量效关系。结论　血压平具有逆转RHR左室重构的作用 ,其降低血压、降低血清PCⅢ含量、抑制Ⅲ型胶原合成、防治心肌纤维化及降低原癌基因C -myc和C -fos的表达、抑制心肌细胞肥大、减轻左心室肥厚 ,是其逆转2K1CRHR左室重构的部分机制。     

缬沙坦对肾血管性高血压大鼠心肌肥厚及结缔组织生长因子表达的影响

目的:研究肾血管性高血压(RVH)大鼠心肌肥厚及结缔组织生长因子(CTGF)的表达情况,探讨缬沙坦逆转左室重构的可能机制。方法:用两肾一夹方法构建RVH大鼠模型。以左心室重量(LVW)、LVW与体重比值(LVW/BW)作为心肌肥厚的指标,分别应用RT-PCR法和免疫组织化学染色法检测CTGF的mRNA和蛋白质的表达。结果:①RVH大鼠术后第8周出现心肌肥厚,第12周进一步加重。缬沙坦治疗后,心肌肥厚明显减轻(P<0.01)。②RVH未治疗组CTGF mRNA及蛋白表达与假手术组比较显著增加;缬沙坦治疗4或8周后,其表达较相应未治疗组显著降低(P<0.05)。结论:RVH大鼠CTGF表达增多,缬沙坦能部分抑制其过度表达。这可能是AT受体阻滞剂预防或逆转心肌肥厚重构的机制之一。     

贝那普利和氯沙坦联合阻断肾素—血管紧张素系统对自发性高血压大鼠左心室重构的影响

目的探讨贝那普利和氯沙坦单独与联合治疗对改善及逆转老龄自发性高血压大鼠左心室重构的影响。方法选55周龄Wistar京都大鼠18只,同龄自发性高血压大鼠54只,随机抽取Wistar京都大鼠和自发性高血压大鼠各6只检测,以确定左心室肥厚,其余分为Wistar京都大鼠对照组、自发性高血压大鼠对照组、贝那普利组10 mg/(kg.d)、氯沙坦组30 mg/(kg.d)及贝那普利10 mg/(kg.d) 氯沙坦15 mg/(kg.d)联合用药组。监测动脉收缩压及左心室质量指数,光镜观察心肌组织结构改变,免疫组织化学法测心肌胶原纤维表达,TUNEL末端标记法进行细胞凋亡检测。结果各药物干预组均可降低左心室质量指数(P<0.01),改善心肌组织结构的改变,降低总胶原及Ⅰ型胶原表达(P<0.01),并轻度降低Ⅲ型胶原表达,均以联合用药组更显著(P<0.01);贝那普利组心肌细胞凋亡率显著高于自发性高血压对照组(P<0.01),氯沙坦组及联合用药组心肌细胞凋亡率显著降低(P<0.01)。结论贝那普利和氯沙坦联合治疗自发性高血压大鼠对改善和逆转左心室重构优于单剂。     

血管紧张素Ⅱ-醛固酮诱导肾性高血压大鼠心肌肥厚发生:钙调神经磷酸酶抑制因子的作用

目的:探讨一肾一夹肾性高血压大鼠模型中,心肌组织中钙调神经磷酸酶(CaN)抑制因子(calcineurin-inhibi-tor,Cain)表达的变化,以及血浆中相关活性因子的变化。方法:将21只健康雄性Wistar大鼠,随机分为3组(n=7),即假手术组、手术组(通过一肾一夹法复制肾性高血压大鼠)及螺内酯组:以螺内酯20 mg/(kg.d)灌胃;实验14 d后,大鼠称质量后抽血处死,分别计算左心室质量(LVW)、全心质量(HW)以及二者与体质量(BW)的比值。采用放射免疫测定法检测血浆醛固酮(Ald)及血管紧张素Ⅱ(AngⅡ)的含量。以蛋白印迹杂交的方法,测定心肌组织中Cain表达的变化。结果:与假手术组比较,手术组大鼠的LVW/BW及HW/BW比值显著增加(P0.05)、血浆Ald和AngⅡ的水平、及Cain的表达的显著增加(P0.01);而与手术组比较,螺内酯组大鼠的LVW/BW比值显著减少(P0.05)、血浆AngⅡ的水平及Cain的表达均显著减少(P0.01)。结论:通过一肾一夹手术,诱导机体内源性Ald和AngⅡ增加,导致大鼠心肌肥厚反应的发生。同时,机体内源性Cain表达的增加,以抑制CaN信号通路介导的心肌肥厚反应。螺内酯通过阻断Ald与其受体结合,可以抑制心肌肥厚的发生。     

肝素结合表皮生长因子在高血压大鼠心肌表达及氯沙坦对其影响

目的探讨肝素结合表皮生长因子(HB-EGF)在自发高血压大鼠(SHR)心肌表达情况及氯沙坦对其影响.方法取16只8周龄自发性高血压大鼠,随机分为两组,每组8只:氯沙坦干预组,给予氯沙坦30 mg/kg*d溶于饮水灌胃治疗;SHR阳性对照组给予正常饮水.另有8只同龄同源雄性正常血压Wistar-kyoto大鼠(WKY)组作为正常对照组.实验周期12周.观察血压、左室重量/体重(LVW/BW);逆转录多聚酶链反应(RT-PCR)和免疫组化实验检测各组大鼠HB-EGF mRNA的表达情况.结果正常对照组和氯沙坦组血压和LVW/BW均底于SHR阳性对照组;SHR阳性对照组HB-EGF mRNA表达均高于正常对照组和氯沙坦组;氯沙坦组HB-EGF mRNA表达高于正常对照组.结论肝素结合表皮生长因子在自发高血压大鼠组表达明显增加而氯沙坦能部分阻断HB-EGF mRNA的表达提示HB-EGF mRNA可能在高血压发生发展过程中起了一定作用.     

缬沙坦对肾性高血压大鼠心肌肥厚及富脯氨酸蛋白酪氨酸激酶表达的影响

背景和目的富脯氨酸蛋白酪氨酸激酶(Pyk2)是一种新发现且活跃的酪氨酸蛋白激酶,该酶能催化多种含 SH 同源域2的底物蛋白磷酸化,参与细胞的生长、增殖和分化。本文以肾性高血压大鼠(RHR)为模型,研究心肌中 Pyk2的表达情况,探讨缬沙坦逆转左室重构的可能机制。方法制备两肾一夹肾性高血压大鼠模型;将大鼠随机分为假手术组、模型组和缬沙坦组[术后第29天给予缬沙坦30 mg/(kg·d)];分别于术前及术后第1、4、8和12周测定动脉血压和心肌肥厚指数,用免疫印迹法检测心肌组织中 Pyk2及其磷酸化表达。结果术后4周已发生心肌肥大,8～12周心肌肥大进一步加重,缬沙坦能显著降低肾性高血压大鼠的血压,并能有效抑制心肌肥厚的形成(P<0.01);术后大鼠心肌组织 Pyk2活性逐渐增加(1周时,P<0.05,4、8、12周时 P<0.01);缬沙坦降低Pyk2及其磷酸化表达水平,与同周龄模型组相比差异有非常显著意义(P<0.01)。结论 Pyk2及磷酸化在 RHR心肌绀织内表达增高,且与心肌肥厚相关;缬沙坦能下调 Pyk2的表达和磷酸化变化。这可能是血管紧张素Ⅱ受体拮抗剂逆转心肌肥厚重构的机制之一。     

缬沙坦对肾性高血压大鼠心肌肥厚及富脯氨酸蛋白酪氨酸激酶表达的影响

背景和目的 富脯氨酸蛋白酪氨酸激酶(Pyk2)是一种新发现且活跃的酪氨酸蛋白激酶,该酶能催化多种含SH同源域2的底物蛋白磷酸化,参与细胞的生长、增殖和分化.本文以肾性高血压大鼠(RHR)为模型,研究心肌中Pyk2的表达情况,探讨缬沙坦逆转左室重构的可能机制.方法 制备两肾一夹肾性高血压大鼠模型;将大鼠随机分为假手术组、模型组和缬沙坦组[术后第29天给予缬沙坦30 mg/(kg·d)];分别于术前及术后第1、4、8和12周测定动脉血压和心肌肥厚指数,用免疫印迹法检测心肌组织中Pyk2及其磷酸化表达.结果 术后4周已发生心肌肥大,8～12周心肌肥大进一步加重,缬沙坦能显著降低肾性高血压大鼠的血压,并能有效抑制心肌肥厚的形成(P＜0.01);术后大鼠心肌组织Pyk2活性逐渐增加(1周时,P＜0.05,4、8、12周时P＜0.01);缬沙坦降低Pyk2及其磷酸化表达水平,与同周龄模型组相比差异有非常显著意义(P＜0.01).结论 Pyk2及磷酸化在RHR心肌组织内表达增高,且与心肌肥厚相关;缬沙坦能下调Pyk2的表达和磷酸化变化.这可能是血管紧张素Ⅱ受体拮抗剂逆转心肌肥厚重构的机制之一.     

氯沙坦对肾血管性高血压大鼠心肌细胞肿瘤坏死因子α表达的影响

目的观察氯沙坦对肾血管性高血压大鼠心肌细胞肿瘤坏死因子α(TNF-α)表达影响。方法实验采用两肾一夹(2K1C)的方法建立肾血管性高血压(RVH)大鼠模型,将大鼠随机分为假手术组、高血压模型组和高血压模型 氯沙坦治疗组(20mg/kg.d);用鼠尾动脉测压法记录每周血压变化,实验末取心脏,并计算心脏指数(CI:心肌重量/体重);ELISA法和免疫组织化学法分别测定各组心肌TNF-α的表达。结果氯沙坦能明显降低肾血管性高血压大鼠的血压(P<0.01)和CI(假手术组:2.86±0.37比高血压模型组:4.12±0.27比氯沙坦组:3.35±0.62,P<0.05)、显著抑制肾血管性高血压大鼠心肌TNF-α的表达[ELISA法:假手术组:1.1±0.1比高血压模型组:31.3±3.0比氯沙坦组:(2.3±0.2)ng/mg,P<0.05]。结论氯沙坦能有效逆转心室重构,其机制可能与降低心肌中TNF-α的表达有关。     

心舒康对肾性高血压大鼠血管紧张素Ⅱ受体1表达的影响

目的观察心舒康对肾性高血压大鼠血管紧张素Ⅱ受体1表达的影响。方法观察肾性高血压大鼠经心舒康治疗后的收缩压、左心室质量/体质量(LVW/BW)的变化。采用免疫组织化学法检测心肌组织血管紧张素Ⅱ受体1表达水平的变化。结果经中药复方心舒康治疗6周后,大鼠的收缩压明显降低,LVW/BW明显降低,左心室心肌组织中血管紧张素Ⅱ受体1的表达明显减少。结论心舒康能明显降低血压,能够降低LVW/BW,抑制心肌组织血管紧张素Ⅱ受体1的上调。     

氯沙坦对肾血管性高血压大鼠心肌细胞肿瘤坏死因子α表达的影响

目的 观察氯沙坦对肾血管性高血压大鼠心肌细胞肿瘤坏死因子α(TNF-α)表达影响.方法实验采用两肾一夹(2K1C)的方法建立肾血管性高血压(RVH)大鼠模型,将大鼠随机分为假手术组、高血压模型组和高血压模型 氯沙坦治疗组(20 mg/kg·d);用鼠尾动脉测压法记录每周血压变化,实验末取心脏,并计算心脏指数(CI:心肌重量/体重);ELISA法和免疫组织化学法分别测定各组心肌TNF-α的表达.结果 氯沙坦能明显降低肾血管性高血压大鼠的血压(P＜0.01)和CI(假手术组:2.86±0.37比高血压模型组:4.12±0.27比氯沙坦组:3.35±0.62,P＜0.05)、显著抑制肾血管性高血压大鼠心肌TNF-α的表达[ELISA法:假手术组:1.1±0.1比高血压模型组:31.3±3.0比氯沙坦组:(2.3±0.2)ng/mg,P＜0.05].结论 氯沙坦能有效逆转心室重构,其机制可能与降低心肌中TNF-α的表达有关.     

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.