Tachykinin dysfunction attenuates monocrotaline-induced pulmonary hypertension
Tachykinin dysfunction attenuates monocrotaline-induced pulmonary hypertension
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DOI：
10.1016/s0041-008x(02)00070-4
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发表时间：
2003-03-15
影响因子：
3.8
通讯作者：
Lai, YL
中科院分区：
文献类型：
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作者：
Chen, MJ;Lai, YL
本研究采用双链速激肽原（ds PPT）RNA和神经激肽受体（NK）拮抗剂，探讨了速激肽在野百合碱（MCT）诱导的肺动脉高压中的功能障碍。在这里，我们显示了通过双链RNA，RNA干扰（RNAi），在发育完全的大鼠组织中减弱PPT基因表达的可能性。我们在系列I中设计了四组实验（对照、MCT、RNAi + MCT和溶剂+ MCT），在系列2中设计了七组实验（对照、MCT、MCT + CP-96345-3.4、MCT + CP-96345-10、MCT + CP-96344-10、MCT + SR-48968和MCT + SR-48965）。对照组注射生理盐水。MCT给药大鼠接受单次MCT注射（60 mg/kg sc）。MCT前1天，在RNAi + MCT组大鼠双侧结状神经节中显微注射ds PPT RNA，或在溶剂+ MCT组中显微注射溶剂。从MCT给药后第1天开始，MCT给药大鼠每日注射NK 1受体拮抗剂CP-96345（3.4或10 mg/kg ip）或其无活性对映体CP-96344（10 mg/kg ip）。从MCT后1天开始，每隔一天向MCT给药大鼠注射NK受体拮抗剂SR-48968（3 mg/kg ip）或其非活性对映体SR-48965（3 mg/kg ip）。在MCT后2周（系列1）或3周（系列2）进行功能研究。MCT诱导右心室肥大，以及肺动脉压、PPT mRNA（结状神经节和肺组织）和肺组织P物质水平升高。所有上述MCT诱导的改变均被RNAi或NK受体拮抗剂减弱。我们得出结论，速激肽在MCT诱导的肺动脉高压中起重要作用。(C)2003 Elsevier Science（美国）。All rights reserved.
We explored the dysfunction of tachykinins on monocrotaline (MCT)-induced pulmonary hypertension by using double-stranded preprotachykinin (ds PPT) RNA and neurokinin receptor (NK) antagonists. Here, we showed the possibility to attenuate the PPT gene expression by ds RNA, RNA interference (RNAi), in fully developed tissue of rats. We designed four groups (control, MCT, RNAi + MCT, and solvent + MCT) of experiments in series I and seven groups (control, MCT, MCT + CP-96345-3.4, MCT + CP-96345-10, MCT + CP-96344-10, MCT + SR-48968, and MCT + SR-48965) of experiments in series 2. Rats in the control groups received saline injection. MCT-treated rats received a single MCT injection (60 mg/kg sc). One day prior to MCT, bilateral nodose ganglia were microinjected with ds PPT RNA in rats of the RNAi + MCT group or with solvent in the solvent + MCT group. Beginning from I day post-MCT, MCT-treated rats received a daily injection of the NK1 receptor antagonist, CP-96345 (3.4 or 10 mg/kg ip) or its inactive enantiomer CP-96344 (10 mg/kg ip). The NK, receptor antagonist SR-48968 (3 mg/kg ip) or its inactive enantiomer SR-48965 (3 mg/kg ip) was injected to MCT-treated rats every other day starting 1 day post-MCT. Functional study was carried out 2 weeks (series 1) or 3 weeks (series 2) after MCT. MCT induced right ventricular hyper-trophy, as well as increases in pulmonary arterial pressure, PPT mRNA (nodose ganglia and lung tissue), and lung tissue substance P level. All of the above MCT-induced alterations were attenuated by either RNAi or NK receptor antagonists. We conclude that tachykinins play an important role in MCT-induced pulmonary hypertension. (C) 2003 Elsevier Science (USA). All rights reserved.