新内皮素受体拮抗剂CPU-0213 对左甲状腺素诱导的大鼠肥大心肌中基质金属蛋白酶及其抑制剂表达的影响

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (3): 281-284.

新内皮素受体拮抗剂CPU-0213 对左甲状腺素诱导的大鼠肥大心肌中基质金属蛋白酶及其抑制剂表达的影响

刘青, 戴德哉

中国药科大学药理研究室, 南京210009, 江苏

收稿日期:2003-09-20 修回日期:2003-11-11 出版日期:2004-03-26 发布日期:2020-11-21
作者简介:刘青, 女, 在读博士, 从事心血管药理学研究。

Influence of a new endothelin receptor antagonist CPU-0213 on expression of MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L-thyroxin

LIU Qing, DAI De-Zai

Research Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2003-09-20 Revised:2003-11-11 Online:2004-03-26 Published:2020-11-21

摘要/Abstract

摘要： 目的:观察左甲状腺素(L-thy) 诱导的大鼠肥大心肌中基质金属蛋白酶(MMPs) 及其抑制剂(TIMPs) 的基因表达和新内皮素受体拮抗剂CPU-0213 对基因表达的影响。方法:雄性SD 大鼠, 随机分成3 组, 除对照组外, 大鼠皮下注射L-thy(0.4 mg·kg^-1·d^-1) 共10 d, 在d 7 给予CPU-0213(ig, 100 mg·kg^-1·d^-1) 干预, 连续3 d 。动物处死后取大鼠心脏测定心肌组织中总胶原含量, 用半定量RT-PCR 方法检测心肌组织中MMP-2,MMP-9 及其抑制剂TIMP-1, TIMP-2 的基因表达。结果:L-thy 诱导的大鼠肥大心肌中, MMPs 的表达下调。TIMPs 的表达上调。给予CPU-0213 后TIMP-1 的表达下调,TIMP-2 的表达基本不改变, MMPs 的表达变化不明显。结论:CPU-0213 通过抑制MMPs 的表达, 增加心肌胶原的含量, 改善心肌病理性重构。

关键词: 左甲状腺素, 基质金属蛋白酶, 基质金属蛋白酶抑制剂, RT-PCR, CPU-0213

Abstract: AIM: To observe the alterations of matrix metalloproteinases (MMPs) and TIMPs (the inhibitor of MMPs) and to study the influence of a new endothelin receptor antagonist CPU-0213 on MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L-thyroxin (L-thy).METHODS: Male Sprague-Dawley rats were randomly divided into three groups and sc administrated suspension of L-thy (0.4 mg·kg ^-1·d ^-1) for consecutive 10 d except for normal group.On the 7th day, the rats treated with L-thy were given CPU-0213 (ig, 100 mg · kg ^-1·d ^-1) for 3 d.The whole collagen content in myocardium was measured.Relative LV myocardial mRNA levels of MMPs (MMP-2, MMP-9) and tissue inhibitor (TIMP-1, TIMP-2) were detected with semi-quantitative RT-PCR.RESUITS: The whole collagen content in myocardium induced by L-thy decreased but it increased in the group CPU-0213.The expression of MMPs (MMP-2, MMP-9) mRNA was downregulated in L-thy group and the expression of TIMPs mRNA was upregulated in L-thy group markedly.Treated with CPU-0213, the expressions of MMP-9 and TIMP-1 mRNA were downregulated, whereas the expression of MMP-2 mRNA coming from CPU-0213 group tended to upregulate.But there was no statistical significance among these groups. CONCLUSION: CPU-0213 can inhibit the expression of MMPs and increase collagen content, which can improve heart function.

Key words: L-thyroxin, metalloproteinases, TIMPs, RT-PCR, CPU-0213

中图分类号:

R965.1

刘青, 戴德哉. 新内皮素受体拮抗剂CPU-0213 对左甲状腺素诱导的大鼠肥大心肌中基质金属蛋白酶及其抑制剂表达的影响[J]. 中国临床药理学与治疗学, 2004, 9(3): 281-284.

LIU Qing, DAI De-Zai. Influence of a new endothelin receptor antagonist CPU-0213 on expression of MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L-thyroxin[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(3): 281-284.

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