医药导报
醫藥導報
의약도보
HERALD OF MEDICINE
2015年
5期
569-573
,共5页
匹伐他汀%野百合碱%肺动脉高压%血管平滑肌
匹伐他汀%野百閤堿%肺動脈高壓%血管平滑肌
필벌타정%야백합감%폐동맥고압%혈관평활기
Pitavastatin%Monocrotaline%Pulmonary arterial hypertension%Vascular smooth muscle
目的：探讨匹伐他汀在防治肺动脉高压中的作用及其可能机制。方法雄性斯泼累格·多雷( SD)大鼠50只,随机分为5组(n=10),分别为正常对照组、模型对照组、匹伐他汀预防组(1 mg·kg-1·d-1)和匹伐他汀大剂量(3 mg·kg-1·d-1)治疗组、小剂量(1 mg · kg-1· d-1)治疗组。除正常对照组外,其余4组均通过皮下注射野百合碱55 mg·kg-1,诱导大鼠形成肺动脉高压。8周后,比较各组存活率、平均肺动脉高压(mPAP)、血小板源性生长因子-B(PDGF-B)、Rac1mRNA的表达及白细胞介素-6(IL-6)分泌水平。结果匹伐他汀预防组、正常对照组大鼠均存活,匹伐他汀小剂量治疗组、大剂量治疗组与模型对照组小鼠存活率分别为60.0%,80.0%,40.0%(P<0.01)；与模型对照组比较,匹伐他汀治疗组mPAP均降低(均P<0.01),肺组织PDGF-B表达、IL-6分泌及Rac1基因表达均降低(均P<0.01)。结论匹伐他汀可能是通过对Rac1基因和PDGF-B表达的调节以抑制肺动脉平滑肌细胞增殖和抑制IL-6分泌等机制防治肺动脉高压。
目的：探討匹伐他汀在防治肺動脈高壓中的作用及其可能機製。方法雄性斯潑纍格·多雷( SD)大鼠50隻,隨機分為5組(n=10),分彆為正常對照組、模型對照組、匹伐他汀預防組(1 mg·kg-1·d-1)和匹伐他汀大劑量(3 mg·kg-1·d-1)治療組、小劑量(1 mg · kg-1· d-1)治療組。除正常對照組外,其餘4組均通過皮下註射野百閤堿55 mg·kg-1,誘導大鼠形成肺動脈高壓。8週後,比較各組存活率、平均肺動脈高壓(mPAP)、血小闆源性生長因子-B(PDGF-B)、Rac1mRNA的錶達及白細胞介素-6(IL-6)分泌水平。結果匹伐他汀預防組、正常對照組大鼠均存活,匹伐他汀小劑量治療組、大劑量治療組與模型對照組小鼠存活率分彆為60.0%,80.0%,40.0%(P<0.01)；與模型對照組比較,匹伐他汀治療組mPAP均降低(均P<0.01),肺組織PDGF-B錶達、IL-6分泌及Rac1基因錶達均降低(均P<0.01)。結論匹伐他汀可能是通過對Rac1基因和PDGF-B錶達的調節以抑製肺動脈平滑肌細胞增殖和抑製IL-6分泌等機製防治肺動脈高壓。
목적：탐토필벌타정재방치폐동맥고압중적작용급기가능궤제。방법웅성사발루격·다뢰( SD)대서50지,수궤분위5조(n=10),분별위정상대조조、모형대조조、필벌타정예방조(1 mg·kg-1·d-1)화필벌타정대제량(3 mg·kg-1·d-1)치료조、소제량(1 mg · kg-1· d-1)치료조。제정상대조조외,기여4조균통과피하주사야백합감55 mg·kg-1,유도대서형성폐동맥고압。8주후,비교각조존활솔、평균폐동맥고압(mPAP)、혈소판원성생장인자-B(PDGF-B)、Rac1mRNA적표체급백세포개소-6(IL-6)분비수평。결과필벌타정예방조、정상대조조대서균존활,필벌타정소제량치료조、대제량치료조여모형대조조소서존활솔분별위60.0%,80.0%,40.0%(P<0.01)；여모형대조조비교,필벌타정치료조mPAP균강저(균P<0.01),폐조직PDGF-B표체、IL-6분비급Rac1기인표체균강저(균P<0.01)。결론필벌타정가능시통과대Rac1기인화PDGF-B표체적조절이억제폐동맥평활기세포증식화억제IL-6분비등궤제방치폐동맥고압。
Objective To investigate the effects and mechanism of pitavastatin on monocrotaline ( MTC )-induced pulmonary arterial hypertension ( PAH) in rats. Methods A total of 50 male Sprague-Dawley rats were randomly divided into five groups (n=10 each):pitavastatin treatment at low dose (1 mg·kg-1·d-1),treatment at high dose (3 mg·kg-1·d-1), pitavastatin prevention regimen (1 mg·kg-1·d-1), model control group, and the normol control group. PAH was induced by applying a single subcutaneous injection of MTC(55 mg·kg-1)in the first four groups of rats. The treatment lasted for 8 weeks. At the end of the study, survival rates and mean pulmonary arterial pressure ( mPAP ) among groups were compared. The expression levels of platelet-derived growth factor-B ( PDGF-B) and IL-6, Rac1 mRNA in small pulmonary artery were also detected. Results All rats in the prevention protocol and normal control group survived. Pitavastatin treatment improved survival in the treatment protocol(P<0. 01). The survival rate in the low dose, high dose, and model control group was 60. 0%, 80. 0%, and 40. 0%, respectively. Pitavastatin in both prevention or treatment protocol significantly lowered mPAP (P<0. 01). Pitavastatin also inhibited PDGF-B and IL-6 expression (P<0. 01),and inhibited Rac1 mRNA expression in lung tissues (P<0. 01). Conclusion Pitavastatin reduces mPAP in the MTC-induced PAH rat model, the mechanism of which may be related to inhibition of Rac1 expression,smooth muscle cell proliferation and inflammatory mediator IL-6.
