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 0 2 13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 .4mg·kg-1·d-1)共 10d ,在d 7给予CPU 0 2 13(ig ,10 0mg·kg-1·d-1)干预 ,连续 3d。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 0 2 13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 0 2 13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。
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.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2004年第3期281-284,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金重点项目 (№ 3 0 2 3 0 170 )
国家自然科学基金项目(№ 3 0 1710 78)
