舒血宁注射液对急性脑梗死患者血浆内皮素和血液流变学指标的影响

目的 观察舒血宁注射液对急性脑梗死患者血浆内皮素和血液流变学指标的影响。方法 选取医院2012年1月至2013年12月收治的300例急性脑梗死患者,随机分为对照组与治疗组,各150例。对照组患者给予溶栓、抗凝、保护脑细胞、降压等常规治疗,治疗组在此基础上加用舒血宁注射液。观察两组患者的临床疗效,检测血浆内皮素和血液流变学指标,记录药品不良反应。结果 治疗组的总有效率为89.33%,明显高于对照组的76.67%,神经功能缺损评分下降幅度也大于对照组,差异均有统计学意义（P〈0.05）;治疗组患者血浆内皮素和血液流变学指标的改善程度优于对照组（P〈0.05）。治疗过程中未见明显药品不良反应。结论 舒血宁注射液治疗急性脑梗死能提高临床疗效,降低血浆内皮素水平并改善血液流变学指标,安全性高,值得临床推广。     

氢氯噻嗪联合缬沙坦治疗老年高血压的临床研究

目的 探讨氢氯噻嗪联合缬沙坦治疗老年高血压的临床疗效。方法 2011年7月—2014年6月上海交通大学医学院附属新华医院收治的老年原发性高血压患者96例,随机分为对照组（48例）和治疗组（48例）,对照组口服缬沙坦胶囊80 mg/d。治疗组口服氢氯噻嗪片12.5 mg/d,其他同对照组。两组均持续治疗2个月。治疗后,评价两组的临床疗效,同时比较两组治疗前后收缩压（SBP）、收缩压变异度（SBPV）、舒张压（DBP）、舒张压变异度（DBPV）、血压晨峰（MBPS）的控制率、一氧化氮、内皮素的变化。结果 治疗组和对照组的总有效率分别为97.92%、83.33%,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者平均SBP、SBPV、DBP、DBPV、内皮素均较治疗前显著降低,一氧化氮水平显著升高,同组治疗前后差异有统计学意义（P<0.05）,且治疗后治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义（P<0.05）。治疗组MBPS控制率为93.75%,对照组为81.25%,两组比较差异有统计学意义（P<0.05）。结论 氢氯噻嗪联合缬沙坦治疗老年高血压具有较好的临床疗效,可显著降低患者血压和血压昼夜变异度,可能与调节内皮一氧化氮和内皮素水平有关。     

阿托伐他汀联合坎地沙坦酯治疗原发性高血压的临床研究

目的探究阿托伐他汀联合坎地沙坦酯治疗原发性高血压的临床疗效。方法选取2012年1月—2014年11月义马煤业集团股份有限公司收治的原发性高血压患者300例,随机分为对照组和治疗组,每组150例。对照组口服坎地沙坦酯片,2片/次,1次/d。治疗组口服阿托伐他汀钙片1片/次,1次/d,坎地沙坦酯片的用法用量同对照组。两组患者均连续治疗10周。观察两组的临床疗效,同时比较治疗前后两组患者收缩压、舒张压、超敏C反应蛋白(hs-CPR)、内皮素(ET)、一氧化氮(NO)的变化。结果治疗后,两组总有效率分别为76.67%、90.67%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者收缩压、舒张压、hs-CRP、ET均较治疗前显著降低,NO显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义(P0.05)。结论阿托伐他汀联合坎地沙坦酯治疗原发性高血压具有较好的临床疗效,可改善患者的血管内皮功能和炎症反应,值得在临床上进一步推广和应用。     

In vivo imaging reveals an essential role of vasoconstriction in rupture of the ovarian follicle at ovulation

Rupture of the ovarian follicle releases the oocyte at ovulation, a timed event that is critical for fertilization. It is not understood how the protease activity required for rupture is directed with precise timing and localization to the outer surface, or apex, of the follicle. We hypothesized that vasoconstriction at the apex is essential for rupture. The diameter and blood flow of individual vessels and the thickness of the apical follicle wall were examined over time to expected ovulation using intravital multiphoton microscopy. Vasoconstriction of apical vessels occurred within hours preceding follicle rupture in wild-type mice, but vasoconstriction and rupture were absent in Amhr2^cre/+SmoM2 mice in which follicle vessels lack the normal association with vascular smooth muscle. Vasoconstriction is not simply a response to reduced thickness of the follicle wall; vasoconstriction persisted in wild-type mice when thinning of the follicle wall was prevented by infusion of protease inhibitors into the ovarian bursa. Ovulation was inhibited by preventing the periovulatory rise in the expression of the vasoconstrictor endothelin 2 by follicle cells of wild-type mice. In these mice, infusion of vasoconstrictors (either endothelin 2 or angiotensin 2) into the bursa restored the vasoconstriction of apical vessels and ovulation. Additionally, infusion of endothelin receptor antagonists into the bursa of wild-type mice prevented vasoconstriction and follicle rupture. Processing tissue to allow imaging at increased depth through the follicle and transabdominal ultrasonography in vivo showed that decreased blood flow is restricted to the apex. These results demonstrate that vasoconstriction at the apex of the follicle is essential for ovulation.During ovulation in typically mono-ovulatory species such as humans, as well as in poly-ovulatory species such as rodents, the oocyte is released from the preovulatory follicle by extrusion through a rupture site on the outer surface, or apex, of the follicle, which protrudes from the surface of the ovary (1). Precise timing and accurate spatial localization of rupture at the apex are essential to allow capture of the oocyte by a hormonally primed oviduct where fertilization occurs, but the mechanisms involved are not yet understood. The rupture site breaches multiple layers of cells and their associated extracellular matrix and basement membranes (2). These include the single layer of epithelial cells that covers the surface of the ovary, the basement membrane that supports it, and the multiple cell layers comprising the wall of the preovulatory follicle. The outer wall of the ovarian follicle contains androgen-secreting theca cells and extensive vasculature. This vasculature consists of an inner and an outer plexus of capillaries with associated arterioles and venules that supply nutrients to the entire follicle (3–5). Underlying the theca and separated from it by a basement membrane is the avascular granulosa cell layer that serves as the major source of estrogen. The oocyte resides in the center of the follicle surrounded by multiple layers of specialized granulosa cells known as “cumulus cells.” In a mature preovulatory follicle, formation of a fluid-filled antral cavity separates the oocyte–cumulus complex from the mural granulosa cells that form the wall of the follicle except at a region known as the “stalk,” which connects the oocyte–cumulus complex to the antral granulosa cells of the follicle wall. At ovulation the oocyte is released from the follicle in association with attached cumulus cells.The preovulatory release of surge levels of luteinizing hormone (LH) from the anterior pituitary acts on receptors in the follicle to trigger events critical for the rupture and remodeling of the follicle and differentiation of granulosa and theca cells into progesterone-producing cells of the corpus luteum. The cumulus cells are induced to secrete a mucoelastic extracellular matrix which causes loosening of contacts between granulosa cells and between granulosa cells and the oocyte, a process known as “cumulus expansion,” which is essential for ovulation (1). Expression of proteases belonging to several major families, including the matrix metalloproteinase, plasminogen activator/plasmin, and ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) families, increases. Simultaneously, follicle cells express protease inhibitors such as tissue inhibitors of metalloproteinases (TIMPs 1–4) and plasminogen activator inhibitors (PAI 1–3) (6, 7). The increase in protease activity is essential for rupture of the follicle and for the breakdown of the basement membrane separating theca and granulosa cells to allow the ingrowth of blood vessels to establish the corpus luteum. The mechanisms that regulate the balance of protease and protease inhibitor activity in the follicle to allow precise rupture at the apex while protecting most of the follicle structure from protease activity are not understood (1, 6, 7).We postulated that vasoconstriction of vessels within the theca at the apex of the follicle is required to promote follicle rupture. Our first approach was to examine mice with conditional expression of a dominant active allele of smoothened (SMO), the transmembrane protein that relays signaling by the hedgehog (HH) pathway. In these Amhr2^cre/+SmoM2 mice, preovulatory follicles develop normally in many respects, including changes in the expression of critical genes in response to the preovulatory LH surge (8, 9). However, follicles fail to rupture, and oocytes remain trapped as the follicles luteinize. The major ovarian phenotype in these mice is a pronounced deficiency of vascular smooth muscle (VSM) surrounding vessels in the theca cell layer, whereas other vessels that are present throughout the stroma of the ovary have normal maturation with VSM. Because VSM is required for vasoconstriction, the mice provided a model to test whether failure of vasoconstriction contributes to anovulation. In additional experiments with wild-type mice, we blocked the increase in the expression of endothelin 2 (Edn2) by granulosa cells that normally occurs within hours before follicle rupture (10, 11). Because EDN2 is a potent vasoconstrictor, this approach allowed us to test the effect on follicle rupture of inhibiting vasoconstriction versus treatment with exogenous compounds to restore vasoconstriction. In addition, treatment of wild-type mice with EDN2 receptor antagonists was used to test the role of EDN2 in vasoconstriction and rupture. Vasoconstriction and changes in the follicle wall were monitored repeatedly relative to the time of ovulation using intravital multiphoton microscopy.     

Involvement of Nax sodium channel in peripheral nerve regeneration via lactate signaling

Na_x, a sodium concentration‐sensitive sodium channel, is expressed in non‐myelinating Schwann cells of the adult peripheral nervous system, but the pathophysiological role remains unclear. We found that functional recovery of the hind paw responses from the sciatic nerve transection was delayed in Na_x knockout ( ) mice. Histological analyses showed a decrease in the number of regenerated myelinated axons in sciatic nerves. The delay in the recovery in mice was improved by lactate and inhibited by a monocarboxylate transporter inhibitor. In vitro experiments using cultured Schwann cells showed that lactate release was enhanced by endothelin (ET)‐1 and blocked by an ET receptor type B antagonist. Here, it is conceivable that Na_x was activated by ET‐1. The amount of lactate release by ET‐1 was lower in mice than in wild‐type mice. These results indicated that Na_x is functionally coupled to ET for lactate release via ET receptor type B and is involved in peripheral nerve regeneration.     

Protective effects of simultaneous splenectomy on small‐for‐size liver graft injury in rat liver transplantation

Splenectomy is an effective technique in living donor liver transplantation (LDLT) with small‐for‐size (SFS) liver grafts for overcoming SFS liver graft injury. However, the protective mechanism of splenectomy is still unclear. The aim of this study was to investigate how splenectomy could attenuate SFS graft injury through the measurement of biochemical factors, particularly the expression of endothelin (ET)‐1, which is a key molecule of microcirculatory disorders by mediating sinusoidal vasoconstriction. We performed rat orthotopic liver transplantation using SFS liver grafts with or without splenectomy. We investigated intragraft expression of ET‐1 mRNA and hepatic protein levels of ET‐1. In addition, portal pressure, hepatic injury and morphological changes, and survival rate were evaluated. In result, intragraft ET‐1 mRNA expression after SFS liver transplantation was significantly downregulated by splenectomy, and hepatic expression of ET‐1 in SFS grafts was rarely observed. Splenectomy inhibited the increase in portal pressure, ameliorated SFS liver graft injury and improved the graft survival rate after SFS liver transplantation. In conclusion, splenectomy improved the SFS liver injury and decreased the expression of ET‐1 by attenuating portal hypertension on SFS liver transplantation. Downregulation of intragraft ET‐1 expression plays important roles in the protective mechanism of splenectomy in SFS liver transplantation.     

运动对大鼠胸主动脉损伤后内皮素和一氧化氮合成酶的影响

用2FFogarty球囊导管剥脱大鼠胸主动脉内皮，观察动脉一氧化氮合成酶（NOS）活性和内皮素（ET）水平的变化及运动对它们的影响。结果发现：动脉损伤4周后血浆和胸主动脉ET的含量较假手术组（SO）升高显著（P＜0．01），运动明显增强损伤动脉NOS活性，抑制ET的生成，较动脉损伤组明显低（P＜0．05）。提示运动增强NOS活性、抑制ET的合成是运动防治内皮损伤和平滑肌细胞异常增殖性疾病的重要机制。     

急性冠脉综合征患者血浆内皮素及外周血单个核细胞内皮素受体mRNA检测

目的:研究急性冠脉综合征(ACS)患者血浆内皮素(ET)水平及外周血单个核细胞ETA及ETB受体mRNA的表达.方法:采用放免法测定36例ACS患者(其中急性心肌梗死(AMI)16例,不稳定型心绞痛(UAP)20例)与20例健康人外周血浆ET水平,逆转录聚合酶链反应(RT-PCR)测定2组外周血单个核细胞ETA及ETB受体mRNA的表达.结果:ACS患者外周血浆ET((0.126±0.013)μg/L)明显高于对照组((0.050±0.006)μg/L)(P＜0.05),AMI亚组血浆ET((0.129±0.016)μg/L)与UAP亚组((0.124±0.011) μg/L)差异无统计学意义(P＞0.05).ACS组ETA受体mRNA表达水平(0.86±0.15)与对照组(0.53±0.16)相比差异有统计学意义(P＜0.05),亚组间ETA受体mRNA表达差异无统计学意义(P＞0.05).2组间ETB受体mRNA表达差异无统计学意义.结论:在ACS的发生过程中血浆ET水平升高,ETA受体mRNA的表达增加,促进了ACS的发生、发展.     

充血性心力衰竭患者血浆一氧化氮、内皮素含量变化及其意义

目的 探讨充血性心力衰竭(CHF)患者血浆一氧化氮(NO)和内皮素(ET)含量变化及其关系。方法 检测65例CHF患者血浆NO和ET含量,另选30例健康体检者作为正常对照组。结果 CHF患者血浆NO和ET水平明显高于正常对照组(P<0.01)。且心衰程度越重,NO和ET水平越高。直线相关分析表明:NO与ET呈正相关(r=0.6457,P<0.001)。结论 血浆NO和ET水平增高是CHF病理生理特征之一。NO和ET共同参与CHF的发生发展过程。