垂体中叶素对脓毒症大鼠心脏功能的影响

目的 探讨垂体中叶素(intermedin,IMD)对脓毒症大鼠心脏功能的影响.方法 采用盲肠结扎穿孔术(cecal ligation and puncture,CLP)复制大鼠脓毒症模型,分为5组,分别为假手术组、CLP组、CLP+常规治疗组(CLP+ CT)、CLP+ CT+ E-IMD早期治疗组、CLP+ CT+ L-IMD晚期治疗组,观察早期(CLP结束时)或晚期(CLP 12 h)给予IMD后大鼠心脏功能、心输出量、心脏指数、每搏指数、氧供、氧耗、血气及动物存活时间、存活率的变化.结果 与假手术组比较,脓毒症后大鼠的心脏功能明显降低;采用常规治疗(包括输液、抗感染以及使用血管活性药物),尽管可以提高动脉血压和中心静脉压,但大鼠的心脏功能无明显改善;早期和晚期给予IMD可明显改善心脏功能;氧供和氧耗明显升高,其中早期给予IMD效果更好,与脓毒症大鼠相比,早期给予IMD后,氧供和氧耗分别升高了148.9％和172.2％;72 h内死亡大鼠的平均存活时间达到23.15 h,72 h存活率为31.2％ (5/16).结论 IMD对脓毒症大鼠的心脏功能有较好的治疗作用.     

肌钙蛋白T、中介素等因子在大鼠房颤模型中的变化及意义

目的 探讨心肌肌钙蛋白T（cardiac tropoin T,cTnT）、中介素（intermedin,IMD）、高敏C反应蛋白（high-sensitivity C-reactive protein,hs-CRP）和同型半胱氨酸（homocysteine,HCY）在大鼠房颤模型中的变化及意义.方法 选用80只雄性SD大鼠,随机分为房颤1日组、房颤4日组、房颤7日组和对照组,每组20只.房颤组通过尾静脉注射乙酰胆碱-氯化钙混合液,每日1次,分别连续注射1、4、7d,建立3组房颤实验模型.对照组不做任何处理.各房颤组大鼠均于造模成功当天心脏取血,对照组与房颤1日组同日心脏取血,采用ELISA测定血清cTnT、IMD、hs-CRP和Hey的水平.结果 房颤1、4、7日组hs-CRP、cTnT水平均高于对照组（P＜0.01）,且其水平随着房颤时间的延长逐渐升高（P＜0.01）.房颤4、7日组HCY水平高于对照组（P＜0.01）,且随着房颤时间的延长而升高（P＜0.01）.房颤4、7日组IMD水平高于对照组,且房颤7日组IMD水平高于房颤1、4日组（P＜0.01）.结论 cTnT、IMD、hs-CRP和Hcy共同参与了房颤的发生和维持,通过干预上述因素可能会对临床房颤的预防和诊治有作用.     

小鼠垂体中叶素对异丙肾上腺素诱导的小鼠心脏肥大的保护作用研究

目的：利用异丙肾上腺素（ISO）诱导的小鼠心脏肥大模型研究小鼠垂体中叶素（IMD）拮抗心脏肥大的药理学作用和机制。方法建立小剂量 ISO 皮下注射诱导心脏肥大的小鼠模型,研究 IMD 给药后的小鼠血流动力学指标和心质量／体质量比,然后利用心脏组织切片评价心肌细胞横截面积、凋亡和纤维化。采用荧光实时定量 PCR 法检测心脏组织的心钠素（ANP）、脑钠肽（BNP）、内源性 IMD 及其受体系统的 mRNA 表达水平。结果与 ISO 诱导的小鼠心脏肥大模型组相比较,腹腔注射 IMD治疗明显降低 ISO 处理所增加的心质量／体质量比和心肌细胞横截面积、心脏肥大标志物 ANP 及 BNP 的 mRNA 水平,以及心肌细胞凋亡率和心肌组织纤维化率。同时,改善心脏功能,左室压力、等容收缩期左心室内压力上升的最大和下降的最小速率、每搏排血量、心输出量和射血分数明显增加,而左心室舒张末期压力显著降低。此外,ISO 处理明显诱导心脏组织内源性 IMD 及其受体的表达。结论 ISO 诱导心脏组织内源性 IMD 及其受体的表达,外源性给与 IMD 治疗可能通过 ISO 活化的 IMD 受体系统实现其拮抗心脏肥大的药理学保护作用。     

Adrenomedullin-2/Intermedin Induces cAMP Accumulation in Dissociated Rat Spinal Cord Cells: Evidence for the Existence of a Distinct Class of Sites of Action

Adrenomedullin-2/intermedin is structurally related to the calcitonin family of peptides, which includes calcitonin gene-related peptide (CGRP), adrenomedullin, and amylin. We recently reported that CGRP and adrenomedullin act through distinct receptors to induce cyclic adenosine monophosphate (cAMP) accumulation in dispersed cells from embryonic rat spinal cord. Here, we investigated the apparent affinity and efficacy of adrenomedullin-2/intermedin for these receptors. Adrenomedullin-2/intermedin competed with [(125)I]-CGRP for binding to specific embryonic spinal cord cells with a pIC(50) of 9.73 +/- 0.06. Interestingly, adrenomedullin-2/intermedin competed for specific [(125)I]-adrenomedullin binding in a biphasic manner with pIC(50) of 9.03 +/- 0.22 and 6.45 +/- 0.24, respectively. Cellular levels of cAMP were increased by adrenomedullin-2/intermedin (pEC(50) 7.84 +/- 0.08) when cells were exposed to this peptide for 10 min at 37 degrees C. This effect was partially inhibited by the non-peptide antagonist BIBN4096BS (pA(2) 6.56 +/- 0.12), the adrenomedullin antagonist hAM(22-52) (pA(2) 6.36 +/- 0.30), and the adrenomedullin/CGRP antagonist CGRP(8-37) (pA(2) 7.24 +/- 0.60). More interestingly, a highly significant effect of adrenomedullin-2/intermedin on cAMP accumulation (pEC(50) 7.3 +/- 0.14) was still observed even in the presence of a mixture of saturating concentrations of BIBN4096BS, hAM(22-52), and the amylin antagonist AC187. Taken together, these data provide evidence for the possible existence of a distinct class of receptor sites for adrenomedullin-2/intermedin in embryonic rat spinal cord cells.     

中叶素抑制大鼠心脏缺血/再灌注损伤

目的研究中叶素(Intermedin,IMD)对大鼠心脏缺血/再灌注(ischemia/reperfusion,I/R)损伤的保护作用及其可能机制。方法Langendorff方法灌流离体心脏,并造成I/R模型,以Power Lab多导生理记录仪记录灌流心脏心功能的变化,收集灌流后心肌组织及灌流液进行生化检测。结果IMD再灌注明显改善I/R造成的心功能抑制和组织损伤,可升高△LVP、LV±dp/dtmax,降低LVDP,增加心率及冠脉流量,同时使心肌LDH、总蛋白和肌红蛋白的漏出及心肌组织MDA生成明显减少,而心肌组织cAMP含量明显增加。且IMD的上述效应与同浓度ADM的效果相近。此外,I/R后心肌IMD受体Bmax和Kd值均增加。结论IMD有明显的抑制心脏I/R损伤的作用,该作用可能通过cAMP途径介导,且IMD抗I/R损伤的作用与强内源性心血管保护肽肾上腺髓质素相仿。     

miR-155在中介素促进肝癌细胞增殖中的作用

目的 MicroRNAs(miRNAs)在恶性肿瘤发生发展过程中起到重要作用,小分子多肽中介素(Intermedin,IMD)可促进肝癌细胞的增殖活性。本文探讨了miR-155在中介素促进肝癌细胞增殖中的作用。方法以CCK-8检测试剂盒检测SMMC7721肝癌细胞增殖,实时定量PCR方法检测增殖细胞核抗原PCNA和miR-155的表达。结果与中介素可以呈时间和剂量依赖关系诱导肝癌SMMC7721细胞的增殖,同时可显著上调miR-155mRNA表达水平;而阻断miR-155可在一定程度上抑制由中介素诱导的SMMC7721细胞增殖。结论中介素促肝癌细胞增殖作用可能与上调miR-155表达相关。     

The pharmacology of adrenomedullin 2/intermedin

Adrenomedullin 2 (AM2) or intermedin is a member of the calcitonin gene-related peptide (CGRP)/calcitonin family of peptides and was discovered in 2004. Unlike other members of this family, no unique receptor has yet been identified for it. It is extensively distributed throughout the body. It causes hypotension when given peripherally, but when given into the CNS, it increases blood pressure and causes sympathetic activation. It also increases prolactin release, is anti-diuretic and natriuretic and reduces food intake. Whilst its effects resemble those of AM, it is frequently more potent. Some characterization of AM2 has been done on molecularly defined receptors; the existing data suggest that it preferentially activates the AM(2) receptor formed from calcitonin receptor-like receptor and receptor activity modifying protein 3. On this complex, its potency is generally equivalent to that of AM. There is no known receptor-activity where it is more potent than AM. In tissues and in animals it is frequently antagonised by CGRP and AM antagonists; however, situations exist in which an AM2 response is maintained even in the presence of supramaximal concentrations of these antagonists. Thus, there is a partial mismatch between the pharmacology seen in tissues and that on cloned receptors. The only AM2 antagonists are peptide fragments, and these have limited selectivity. It remains unclear as to whether novel AM2 receptors exist or whether the mismatch in pharmacology can be explained by factors such as metabolism.     

EH伴左心室肥大患者血浆IMD、血清CysC、CST和Salusin-α测定的临床价值

目的:为探讨原发性高血压(essential hypertension,EH)和EH伴左心室肥厚[EH伴LVH(下分组简称为LVH)]患者的发病机制和测定的临床价值。方法:血浆中叶素(intermedin,IMD)采用放射免疫分析;血清半胱氨酸蛋白酶抑制剂C(CystatinC,CysC)、儿茶酚抑素(catestatin,CST)和新型心血管活性肽Salusin-α测定则应用酶联免疫分析。结果:血浆IMD水平EH组和LVH组均显著地低于正常对照组(P<0.05,P<0.01),且LVH组又显著地低于EH组。血清CysC水平的变化则EH组和LVH组均显著地高于正常对照组(P<0.05,P<0.01),且LVH组又显著地高于EH组。CST水平EH组和LVH组均显著地高于正常对照组(P均<0.05),两组病例比较LVH组略低于EH组(P>0.05)。Salusin-α水平的变化EH组和LVH组均显著低于正常对照组(P均<0.05),两组病例比较LVH组略高于EH组(P>0.05)。结论:四项指标的测定变化,为进一步了解和认识EH和LVH的病理机制可有一定的临床意义。