Association between urotensin II gene polymorphism and pre-eclampsia

Objective

To investigate the association of a specific polymorphism (S89N) in exon 3 of the urotensin II (UTS2) gene in pre-eclampsia.

Study design

One hundred and forty-two subjects, 85 with a diagnosis of pre-eclampsia/eclampsia (group I) and 57 healthy pregnant subjects as a control group (group II), who had been admitted between January 2006 and December 2007, were included. All the subjects were tested for G to A transition in codon 266 in the urotensin II gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The distributions of genotypes and allele frequencies were compared between the groups.

Results

Demographics such as age, gestational age, gravidity, abortion and parity were similar in both groups (p > 0.05). No statistically significant differences were observed between the groups concerning genotype distribution and allele frequency (p = 0.305, p = 0.326, respectively). The observed genotype counts did not deviate significantly from those expected according to the Hardy-Weinberg equilibrium (HWE).

Conclusion

The results of this study suggest that UTS2 single gene (S89N) polymorphism is not associated with pre-eclampsia. Further studies are needed to investigate the prevalence of other single nucleotide gene polymorphisms in pre-eclampsia.     

尾加压素Ⅱ在支气管哮喘中病理生理作用的研究进展

支气管哮喘是呼吸系统的常见疾病之一,是由多种细胞和细胞组分参与的气道慢性炎症性疾病,其发病机制不完全清楚,随着哮喘病理生理和不同炎症表型的知识不断增加,多种因素参与其发病过程的理论也在逐渐被实践证实。其中尾加压素Ⅱ就可能是参与支气管哮喘的发病过程并发挥重要生物学效应的因素之一。本文就尾加压素Ⅱ在支气管哮喘病理生理中的作用予以简要综述。     

尾加压素Ⅱ与原发性高血压关系的研究

目的探讨尾加压素Ⅱ（U-Ⅱ）是否参与了原发性高血压的发病机制。方法选择原发性高血压患者（高血压组,n=90）和正常人（对照组,n=30）,用放射免疫法测定血浆U-Ⅱ的水平,研究原发性高血压对患者的U-Ⅱ的影响。结果对照组与1级高血压组相比,差异无统计学意义;高血压组各级组间U-Ⅱ水平差异有统计学意义（P〈0.05）;正常组、1级、2级、3级高血压组的U-Ⅱ水平分别为7.23±0.99、7.52±1.01、8.15±0.89、8.99±0.98pg/m l,有显著相关性（r系数分别为0.83、0.78、0.80,P〈0.05）。结论 U-Ⅱ可能与原发性高血压的发生发展及高血压的分级呈正相关。     

Urotensin II level is elevated in inflammatory bowel disease patients

It was reported that the urotensin II (U-II) level in inflammatory bowel disease (IBD) patients are significantly higher than in controls. To provide future guidance for the management of cardiovascular risk factors in IBD patients, the sample size of the current study appears to be limited, and more clinical samples to compare U-II levels in IBD patients and controls are needed. This will clarify the possible roles of inflammation factors and related signaling pathways (like EPK1/2, NF-κB and Rho/ROCK) in the pathophysiology of IBD. Therefore, large multicenter studies should be done to confirm the findings and underlying mechanisms in the future.     

血清嗜铬粒蛋白A、尾加压素Ⅱ在小儿慢性心力衰竭中的变化及意义

目的探讨嗜铬粒蛋白A(CgA)、尾加压素Ⅱ(UⅡ)在慢性心力衰竭(CHF)患儿血清中的变化及意义。方法选取58例CHF患儿为心衰组,其中心内膜弹力纤维增生症17例,扩张型心肌病41例;另选取门诊健康体检儿童20例为对照组。采用酶联免疫吸附法(ELISA法)测定血清CgA及UⅡ水平;采用双向侧流免疫法测定氨基末端脑钠肽前体(NT-proBNP)水平;超声心动图测定心室重塑指标;Pearson相关或Spearman秩相关分析血清CgA、UⅡ与心室重塑的相关性。结果心功能Ⅱ级患儿的血清CgA、NT-proBNP水平与对照组的差异无统计学意义(P0.05);CgA、NT-proBNP水平在心功能Ⅲ级、Ⅳ级患儿中高于对照组,并且随着心功能损害加重而升高(P0.05)。UⅡ浓度在心功能Ⅱ级、Ⅲ级、Ⅳ级患儿中均低于对照组,并且随着心功能损害加重而逐渐降低,差异有统计学意义(P0.05)。心内膜弹力纤维增生症与扩张型心肌病患儿间血清CgA、UⅡ水平的差异无统计学意义(P0.05)。血清CgA浓度分别与左心室质量分数(LVMI)、NT-proBNP、心功能分级成正相关(r分别为0.279、0.649及0.778,P0.05),与左室射血分数(LVEF)、左室短轴缩短率(LVFS)、UⅡ成负相关(r分别为-0.369、-0.322及-0.718,P0.05)。血清UⅡ分别与NT-proBNP、心功能分级成负相关(r=-0.472、-0.591,P0.05),而与LVMI、LVEF、LVFS无明显相关性(P0.05)。结论 CgA可能参与CHF患儿心室重塑,血清CgA和UⅡ有可能为心衰的诊断和心功能判断提供参考。     

尾加压素Ⅱ及其受体在人肾透明细胞癌组织中的表达及意义

目的：测定肾透明细胞癌中尾加压素Ⅱ（UⅡ）与其受体（UT-R）的表达量,以期探讨UⅡ与UT—R的表达在肾透明细胞癌发生中的临床意义。方法：对12例。肾透明细胞癌肿瘤组织通过免疫组化检测肾透明细胞癌组织和正常肾组织UⅡ蛋白的表达,并采用逆转录一多聚酶链式反应（RT—PCR）的方法测定肾透明细胞癌组织和正常肾组织UⅡ mRNA和UT-RmRNA的表达量。结果：肾透明细胞癌组织和正常肾组织中有uⅡ蛋白表达。RT-PCR结果显示肾透明细胞癌中UⅡmRNA的表达明显高于正常肾组织0．92±0．09和0．62±0．06（P〈0．01）。UT-R mRNA的表达明显高于正常肾组织0．28±0．01和0．16±0．03（P〈0．01）。结论：肾透明细胞癌中UⅡ和UT—RmRNA高表达提示UⅡ／UT系统可能与肾透明细胞癌的发生、发展有关,UⅡ可能通过自分泌或軎分泌的方式发挥作用。     

Adrenocorticotropic hormone-releasing activity of urotensin I and its fragments in vitro

Adrenocorticotropic hormone (ACTH)-releasing activity of synthetic carp Urotensin I (UI) and its ten synthetic fragments were examined using cultured rat pituitary cells. Both UI(1-41) and rat CRF (rCRF) increased ACTH release in a similar fashion at a concentration range from 10 pm to 100 nm. The potency of UI(1-41) was about one seventh that of rCRF on a molar basis. Four often UI fragments, UI(1-36), UI(4-36), UI(6-36) and UI(1-19) showed relatively strong ACTH-releasing activity, whereas both UI(9–36) and UI(17–36) showed extremely weak ACTH-releasing activity. However, all these fragments showed the activity in a dose-dependent manner parallel with that of UI(1-41). The activity of Ul(1-36) was weaker than Ul(1–41), suggesting that the C-terminal 37-41 sequence is required to express the full ACTH-release activity, although each of four C-terminal fragments, UI(24-36), UI(24-41), UI(29-36) and UI(29-41), exhibited no activity. In summary, the 4-19 amino acid sequence of UI(is important to exhibit ACTH-releasing activity and the C-terminal 37–41 sequence will be necessary to express the full activity.     

尾加压素Ⅱ与动脉粥样硬化

尾加压素Ⅱ(UⅡ)是一种在哺乳动物体内新发现的缩血管活性肽,通过激活G蛋白耦联受体(GPR14)而发挥作用。UⅡ能够促进血管平滑肌细胞增殖、诱导心肌成纤维细胞增殖和胶原合成、刺激心肌细胞肥大、促进巨噬细胞向泡沫细胞转化。血浆或组织UⅡ水平在多种心血管疾病中明显升高,提示UⅡ在心血管系统功能障碍和重塑进程中发挥重要作用。     

Effect of chronic hypoxia on contents of urotensin II and its functional receptors in rat myocardium

The cyclic peptide urotensin II (UII) has recently been cloned in mammals and reported to constrict rat pulmonary arteries potently. An enhanced maximal response was shown in rats exposed to chronic hypoxia. The aim of this study was to investigate changes in plasma and myocardial UII levels and its receptor sites in crude sarcolemma of ventricles from chronic hypoxic rats. We observed that rats exposed to chronic hypoxia for 4 weeks developed pulmonary hypertension and right ventricular hypertrophy. Compared with controls, the UII content in hypoxic rats was increased by 97.5% (45.24 ± 7.1 vs. 22.9 ± 3.24 pg/mg protein, P < 0.01) in the right ventricle and 33.2% (24.89 ± 0.99 vs. 18.68 ± 2.04 pg/mg protein, P < 0.01) in the left ventricle, respectively. However, there was no significant difference in plasma (27.44 ± 3.11 vs. 27.82 ± 5.57 pg/ml, P > 0.05) and lung tissue levels (34.03 ± 4.63 vs. 33.74 ± 4.06 pg/mg protein, P > 0.05) between the control and hypoxic groups. The time course of the binding of [¹²⁵I]UII to crude ventricular sarcolemma was specific and time dependent. Scatchard plot analysis of the data demonstrated that the maximal number of specific binding sites (B _max) in both the right and left ventricles was upregulated in the hypoxic group. Moreover, B _max in the right ventricular specimens was upregulated to a greater extent than in the left ventricle (increased by 114% and 25% in the right and left ventricles, respectively, compared with control group, P < 0.01). In contrast, the UII binding affinity in right and left ventricular membranes from hypoxic rats was decreased (the dissociation constant K _d) increased by 20% and 33%, respectively compared with controls, P < 0.01). These results indicate that UII may act as an autocrine and/or paracrine hormone rather than as a circulating hormone, playing important roles in the development of ventricular hypertrophy induced by chronic hypoxia, and that the pathophysiologi-cal significance of UII in pulmonary and cardiovascular alteration induced by chronic hypoxia deserves further investigation. Received: March 21, 2001 / Accepted: September 28, 2001     

尾加压素Ⅱ促NRK-49F细胞增殖及ECM分泌作用

目的探讨尾加压素Ⅱ（UrotensinⅡ,UⅡ）促进大鼠肾脏成纤维细胞（NRK-49F）增殖及细胞外基质（extracel-lular matrix,ECM）作用。方法分别用含不同浓度UⅡ（10-7、10-8、10-9和10-10mol.L-1）的培养液培养NRK-49F,采用MTT法检测细胞增殖情况,ELISA法检测细胞培养上清中Ⅰ型胶原（collagenⅠ,colⅠ）、Ⅲ型胶原（collagenⅢ,colⅢ）及纤连蛋白（fibronectin,FN）含量;RT-PCR法评价UⅡ抗体、尼莫地平和EDTA对UⅡ诱导NRK-49F colⅠ、colⅢ和FNmRNA过表达的抑制作用。结果 UⅡ可明显促进NRK-49F的增殖,且随着UⅡ浓度的增加而增强;10-9和10-8mol.L-1UⅡ可明显刺激NRK-49F ECM分泌,与对照组比较,差异显著（P〈0.01）;培养液中加入UⅡ抗体、尼莫地平和ED-TA后,NRK-49F colⅠ、colⅢmRNA表达量明显降低,与UⅡ组比较,有统计学意义（P〈0.01）。结论 UⅡ对体外培养的肾间质成纤维细胞有明显的促增殖作用,并且促进其ECM分泌,其机制可能与细胞外Ca2＋内流增加有关。