穿心莲内酯对异丙肾上腺素诱导的心肌肥厚大鼠血管活性物质的影响

目的:观察穿心莲内酯(andrographolide,AP)对异丙肾上腺素(isopropylarterenol,Iso)所致大鼠心肌肥厚的保护作用及其对血管紧张素Ⅱ( angiotensinⅡ,AngⅡ)、心钠素(atrial natriuretic peptide,ANP)、内皮素(endothelin,ET)和一氧化氮( nitric oxide,NO)的影响.方法:以Iso1 mg·kg-1背部皮下注射(sc)连续10 d建立大鼠心肌肥厚模型.选模第2天给药组sc给予低、中、高剂量(0.1,0.3,1.0μmol· kg-1)的AP,溶剂组sc二甲基亚砜,正常组和模型组sc给予生理盐水,连续14 d,末次给药后禁食12 h,取血,分离血清及血浆,取心肌组织并制成10％匀浆.酶活性分析法检测血清及心肌组织乳酸脱氢酶(lactate dehydrogenase,LDH)活性；硝酸还原酶法检测血清NO含量；放射免疫法测定血浆AngⅡ,ANP和ET的含量.结果:与正常对照组相比,模型组大鼠血清LDH活性升高(1 425.4±304.7)U·mL-1,(P＜0.01),心肌组织LDH活性降低(662.5±172.6)U·g-1,(P＜0.05),血浆ET(62.45±12.27) ng·L-1(P＜0.05),含量升高,ANP( 241.82±127.71 )ng·g-1,(P＜0.05)和NO(37.21±2.62) μmol·L-l (P ＜0.01)含量降低.与模型组相比,AP处理后血清LDH活性降低(P＜0.001),组织LDH活性升高(P＜0.05),血浆AngⅡ及ET含量下降(P＜0.05),而血浆ANP含量及血清NO含量升高(P＜0.05).结论:穿心莲内酯可能通过影响大鼠血管活性物质的平衡,抑制RAS系统及ET的合成,增加ANP及NO的合成,从而抑制心肌肥大及心力衰竭的进程,对心脏起保护作用.

Effect of Andrographolide on Vasoactive Substances in Myocardial Hypertrophy Rats

Objective:To observe the protection of andrographolide(AP) on rat’s myocardial hypertrophy induced by isopropylarterenol(Iso),explore balance of vasoactive substance.Method: The rat’s myocardial hypertrophy model is formed through hypodermic injection which extended 10 days at back skin with Iso,1 mg·kg-1·d-1.Once the model is formed,it will be administrated with various doses of AP,dimethyl sulfoxide(DMSO) or normal saline through hypodermic injection from the second day,and the process will extend 14 days.After the last administration,the rat will be in absolute diet status for 12 h and its blood and heart are taken under anesthesia.The activity of lactate dehydrogenase(LDH) in serum and myocardium tissue,the level of NO in serum,and the content of angiotensin Ⅱ(AngⅡ),endothelin(ET) and atrial natriuretic peptide(ANP)in plasma were investigated.Result: Compared with control group,Iso group showed a change about activity of LDH which was increased in serum but decreased in myocardium tissue,a descended level of NO in serum,improved content of AngⅡ and ET while reduced content of ANP in plasma.However,the activity of LDH is depressed in serum and elevated in myocardium tissue in AP groups,furthermore,the level of NO and ANP were enhanced while the content of AngⅡ and ET were reduced in AP groups.Conclusion: AP has a protection on rat’s myocardial hypertrophy caused by Iso,and its mechanism probably result of modulating the homeostasis of AngⅡ,ANP,ET and NO.