愈疡散对胃溃疡大鼠血一氧化氮和内皮素的影响

[目的]探讨愈疡散对胃溃疡大鼠血一氧化氮(NO)和内皮素-1(ET-1)的影响.[方法]采用大鼠冰醋酸胃溃疡模型,设空白对照组(A组)、假手术组(B组)、西药对照组(C组)、愈疡散大、小剂量组(D、E组)、胃溃疡模型组(F组).A、B、F组均灌服0.85%氯化钠溶液;D、E组分别灌服愈疡散5.0g/kg体重、2.5g/kg体重;C组灌服雷尼替丁0.03g/kg体重.于治疗前后分别检测血NO及ET-1.实验结束后,用苏木精-伊红染色对大鼠再生胃黏膜厚度、上皮细胞/腺腔数比值进行观察.[结果]造模7 d,C、D、E、F组血清NO显著降低,血浆ET-1明显升高,与A、B组比较差异有统计学意义(P＜0.05).治疗28 d,D组血清NO显著升高,而血浆ET-1明显降低,与F、E组比较均P＜0.05.再生胃黏膜厚度:D、E、C组明显高于F组(P＜0.05),D、E组与A、B组比较均P＜0.05.上皮细胞/腺腔数比值:A、B组与C、F组,D组与C、F组之间均P＜0.05.[结论]愈疡散促进溃疡愈合,增加胃黏膜的防御能力,提高再生黏膜功能成熟度,可能与其诱导、促进NO合成,反馈性地抑制ET-1释放,维持NO和ET-1的动态平衡有关.     

醛固酮诱导大鼠相关器官组织钙调神经磷酸酶的活化

目的:阐明醛固酮对重要器官组织细胞内信号分子-钙调神经磷酸酶（CaN）的活化作用及其调控机制。方法:取雄性W istar大白鼠21只,分成醛固酮（A ld）组以A ld 18mg/d腹腔内注射4周,螺内酯组以A ld处理同时予螺内酯20 mg.kg-1.d-1灌胃4周及正常对照组。以放免法测得血A ld、血管紧张素II（AngII）和内皮素（ET）浓度;以硝酸盐法测定血NO浓度;以改良底物发色法测得心、脑、脾、肝、肺、肾和主动脉组织CaN活性。结果:醛固酮处理后,大鼠重要脏器的组织CaN活性均升高,分别为心147%、肺95%、脾65%和脑43%,与对照组比较,心、肺、脾和脑组织CaN活化达到统计学意义;血醛固酮浓度较对照组上升了1.62倍;血NO3-浓度明显下降;血中A ld/NO3-上升了2.95倍,ET/NO3-和AngII/NO3-分别上升了0.32倍和0.25倍。以螺内酯干预后,心、肺、脾、脑、肝组织CaN活化程度明显减轻;对大鼠血醛固酮浓度无显著影响,但血AngⅡ浓度下降、NO3-浓度明显升高;A ld/NO3-、ET/NO3-、AngII/NO3-均明显下降。结论:外源性醛固酮可明显升高血中A ld/NO3-浓度比,并显著活化心、肺、脾、脑组织CaN。螺内酯则可全面维护内皮活性因子稳态,下调血A ld/NO3-、AngII/NO3-和ET/NO3-比值,减轻组织CaN的活化效应。     

内皮素系统与心力衰竭

内皮素具有强烈而持久的血管收缩作用,其与慢性心力衰竭的发生、发展及疾病的预后密切相关。长期应用内皮素受体拮抗剂可改善心力衰竭患者的血流动力学、减缓左室重构、增加心脏指数、同时提高生存率。     

Topic-Based,Recent Literature Review on Pulmonary Hypertension

Pulmonary hypertension is a complex condition but a relatively common manifestation of severe cardiopulmonary disease. By contrast, pulmonary arterial hypertension is uncommon and is more prevalent in young women. To better categorize patients and to guide clinical decision-making, 5 diagnostic groups and associated subgroups characterize the spectrum of disease. A multidisciplinary approach to evaluation and treatment is recommended by published guidelines and often entails referral to a designated pulmonary hypertension center. Several key publications during the last couple of years merit review. The PubMed database was searched for English-language studies and guidelines relating to pulmonary hypertension. The following terms were searched, alone and in combination: pulmonary hypertension, pulmonary arterial hypertension, portopulmonary hypertension, and chronic thromboembolic pulmonary hypertension. The focus was on those publications with new information on evaluation and management of pulmonary hypertension between January 1, 2019, and January 31, 2021. Of the subgroups, 2 were of particular interest for this review: portopulmonary hypertension and chronic thromboembolic pulmonary hypertension. Last, available data on the impact of the coronavirus disease 2019 pandemic and newer treatment agents in early trials were selectively reviewed. The review is therefore intended to serve as a practical, focused review of important topics germane to those clinicians caring for patients with pulmonary hypertension.     

内皮素系统与过敏性紫癜的研究进展

过敏性紫癜是儿科常见病之一,其发病机制尚不明确。目前临床以抗过敏治疗为主,治疗后容易复发,并增加了肾脏受累的可能性。近年来该病呈现一定的上升趋势,可能与环境污染导致周围环境中过敏物质增加有关,故值得临床医生高度重视。以往认为内皮素系统参与了这一病理过程,故该文就内皮素系统与过敏性紫癜的关系作以综述。     

Differential effects of oxidative stress on hepatic endothelial and Kupffer cell eicosanoid release in response to endothelin-1

OBJECTIVE: The vasoconstrictor endothelin-1 can induce vasomodulators release like nitric oxide in the liver. Here the authors explored whether endothelin-1 can stimulate endothelial and Kupffer cells release of other vasomodulators under normal and stress conditions. METHODS: Cells were cultured for 24 h and treated with H2O2 (25 microM) for 6 h and subsequently with endothelin-1 (10 nM) for 10 min. Eicosanoid release was assessed in the media by enzyme immunoassay. RESULTS: Endothelin-1 mediated cPLA2 phosphorylation and increased prostaglandin (PG) I2, PGE2 and thromboxane A2 (TXA2) release in endothelial cells while it only increased TXA2 in Kupffer cells. H2O2 significantly increased PGI2, PGE2 and TXA2 in endothelial cells through an upregulation of cyclooxygenase-2, thromboxane synthase A2, and phosphorylation of cPLA2. Endothelin-1-induced PGI2, PGE2, and TXA2 release in endothelial cells were inhibited by H2O2 correlating with the absence of further cPLA2 phosphorylation. In Kupffer cells, H2O2 only increased TXA2 synthesis and further endothelin-1 stimulation of TXA2 was possible through a higher increase in cPLA2. CONCLUSION: These results indicate that under normal conditions endothelial cells play a pivotal role in liver microcirculation regulation. Oxidative stress not only disrupts the basal balance of vasomodulators in the liver but also affects endothelin-1-induced effects in both Kupffer cells and endothelial cells.     

移植肾急性排异反应的临床病理学分类和病理学损伤机理探讨

目的：进一步探讨急性排异的临床病理学特点和发生机理，为临床诊断及治疗提供参考。方法：分析１４４例急性排异的临床病理资料，观察内皮素（ＥＴ）在移植肾组织中的分布和相对含量。结果：１．急性排异反应的病理变化为：①间质水肿、充血、出血，淋巴细胞、单核细胞浸润；②动脉内膜炎、全层炎及血管壁纤维样坏死；③肾小管上皮浊肿、变性、坏死。２．急性间质型排异反应移植肾内ＥＴ的分布以血管内皮细胞损害为主，ＥＴ的相对含量均较血管型组升高，而其它部位无明显升高。急性血管型排异反应移植肾内ＥＴ的分布以肾小球入球动脉为主，呈节段性和局灶性，测定其含量均呈上升趋势，在ＥＴ表达较强的病例中，肾小球毛细血管丛缩小，管腔不易分辨，系膜细胞增生，系膜区扩大。结论：①急性排异反应病变的程度和肾移植的时间并不成正相关，作者根据病变程度和临床工作的需要，将其病理学改变分为轻、中、重三级。在此基础上提出了相应的临床治疗方案。②从形态上证实了ＥＴ升高对移植肾功能损害的状况，说明ＥＴ的产生与升高是排异发生的原因之一。推测应用ＥＴ受体拮抗剂对延缓急性排异反应损伤可能有一定的意义。     

内皮非依赖性舒张功能损伤的生化和超微结构证据

目的探讨高同型半胱氨酸（Hcy）血症是否可导致内皮非依赖性舒张功能（EID）损伤以及可能的损伤机制。方法新西兰兔18只,随机分为正常饮食组（N组）,喂正常饮食及口服蛋氨酸组（M组）,喂服高蛋氨酸饮食（0.8g/kg体质量）。利用高分辨力超声检测内皮依赖性舒张功能（EDD）和EID,同时从耳缘静脉取血检测血浆一氧化氮（NO）、内皮素（ET）及谷胱甘肽过氧化物酶（GSH-PX）的活性。80d后,取兔髂外动脉在透射电镜下观察其超微结构的改变。结果80d后,和N组比较,兔血浆NO的浓度明显降低[（209.54±17.50）μmol/Lvs（386.27±35.67）μmol/L,P<0.05],GSH-PX的活性亦明显降低[（125.75±16.28）活性单位vs（176.62±23.38）活性单位,P<0.05];而ET的浓度却明显升高[（247.40±26.06）ng/Lvs（190.92±34.30）ng/L,P<0.05]。同时,高分辨力超声观察到兔EDD[（-9.26±2.73）%vs（10.89±4.10）%,P<0.01]、EID[（16.94±5.93）%vs（23.70±7.02）%,P<0.05]均明显受到损伤。透射电镜观察发现,兔髂外动脉内皮细胞脱落、细胞膜断裂、线粒体和肌浆网肿胀、染色体浓集靠边,内皮下层基质和胶原增生,内弹力板断裂,平滑肌细胞突破内弹力板。平滑肌细胞也出现明显的超微结构改变:包括肌浆网扩张、线粒体肿胀、染色体浓集,并且胞浆内出现吞噬体小泡。结论高Hcy血症不仅可以导致EDD损伤还可导致EID损伤,血管平滑肌细胞超微结构的改变支持EID可损伤的观点。     

哮喘患儿血浆内皮素含量变化的临床意义

目的探讨血浆内皮素(ET-1)含量变化与哮喘之间的关系。方法应用SN-682型放射免疫r仪计数仪,对50例哮喘患儿在急性期与缓解期分别测定血浆ET-1含量,并与50例正常儿童血浆ET-1含量进行对照,并同期测定血浆肿瘤坏死因子-α(TNF-α)含量。结果哮喘急性期患儿血浆ET-1含量显著高于正常儿童(P<0.01)及缓解期患儿(P<0.05)并与TNFα含量测定呈显著正相关。结论内皮素与哮喘病病情相关,是反映哮喘病病情变化一个有价值的指标。皮质激素治疗能显著降低血浆ET-1含量,可能是其抗气道炎症的作用机制之一。     

大豆异黄酮抑制去势兔动脉粥样硬化形成的实验研究

目的探讨大豆异黄酮对卵巢切除(OVX)兔血脂、内皮素-1(ET-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平及动脉粥样硬化斑块面积的影响.方法28只4月龄雌兔随机分为4组,每组7只.除A组行假手术外,余组均行OVX,并饲以胆固醇饮食,C组予大豆异黄酮,D组予雌二醇,12周后测定血脂、ET-1、TNF-α、IL-6及动脉粥样硬化斑块面积.结果与B组比较,C组、D组总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)均降低,C组高密度脂蛋白胆固醇(HDL-C)增高(P＜0.0 5);C组、D组血浆ET-1、TNF-α、IL-6均降低(P＜0.05),且动脉粥样硬化斑块面积占主动脉总面积的百分比明显降低(P＜0.05).结论大豆异黄酮改善去势兔血脂,并降低ET-1、TNF-α、IL-6水平,可预防及减轻动脉粥样硬化.