中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2012年
48期
3438-3441
,共4页
张志杰%范彦夫%张志英%谢培益%方红城%苏又苏
張誌傑%範彥伕%張誌英%謝培益%方紅城%囌又囌
장지걸%범언부%장지영%사배익%방홍성%소우소
蛋白激酶抑制剂%高血压%心肌肥厚%大鼠%法舒地尔
蛋白激酶抑製劑%高血壓%心肌肥厚%大鼠%法舒地爾
단백격매억제제%고혈압%심기비후%대서%법서지이
Protein kinase inhibitors%Hypertension%Cardiac hypertrophy%Rats%Fasudil
目的 研究Rho激酶抑制剂法舒地尔对自发性高血压大鼠(SHR)左心室心肌肥厚的影响.方法 30只SHR分为5组:SHR对照组；法舒地尔小剂量组(SHRL)、中剂量组(SHRM)、大剂量组(SHRH)和硝苯地平组(XBDP),每组6只；6只Wistar-Kyoto大鼠为正常对照组.给药共8周,分别测量治疗前后尾动脉收缩压(SBP)、左心室重量指数(LVWI)、心肌细胞横径(TDM).RT-PCR和Western印迹法分别检测心肌组织中Rho激酶mRNA和蛋白质的表达.结果 正常对照组大鼠LVWI和TDM明显低于SHR对照组[(2.98±0.05)比(3.16±0.08) mg/g、(18.18±0.75)比(21.32±1.25) μm,P＜0.01],而法舒地尔干预各组大鼠LVWI和TDM明显低于SHR对照组[SHRL组(3.12±0.05)mg/g、SHRM组(3.10±0.07) mg/g、SHRH组(3.08±0.09) mg/g、SHR对照组(3.16±0.08)mg/g,SHRL组(20.11±1.15) μm、SHRM组(19.63±1.62)μm、SHRH组(18.91±1.05) μm、SHR对照组(21.32±1.25) μm,P ＜0.01,P ＜0.05]；XBDP组分别为[(3.14±0.08) mg/g、(21.42±1.23)μm,P＞0.05].与SHR对照组相比,法舒地尔干预各组大鼠心肌组织中Rho激酶mRNA和蛋白质表达明显降低,随剂量增加表达下降[mRNA表达:SHRL组(0 45±0.08)、SHRM组(0.37±0.07)、SHRH组(0.32±0.07)比SHR对照组(0.63±0.07),蛋白质表达:SHRL组(0.78±0.11)、SHRM组(0.73±0.10)、SHRH组(0.68±0.10)、SHR对照组(0.90±0.10),P＜0.01,P＜0.05]；而XBDP组变化不明显[mRNA表达(0.56±0.07)、蛋白质表达(0.85 ±0.10),P＞0.05].结论 Rho激酶抑制剂能够抑制SHR左心室心肌肥厚,其机制可能与下调心肌组织中Rho激酶mRNA和蛋白质的表达有关.
目的 研究Rho激酶抑製劑法舒地爾對自髮性高血壓大鼠(SHR)左心室心肌肥厚的影響.方法 30隻SHR分為5組:SHR對照組；法舒地爾小劑量組(SHRL)、中劑量組(SHRM)、大劑量組(SHRH)和硝苯地平組(XBDP),每組6隻；6隻Wistar-Kyoto大鼠為正常對照組.給藥共8週,分彆測量治療前後尾動脈收縮壓(SBP)、左心室重量指數(LVWI)、心肌細胞橫徑(TDM).RT-PCR和Western印跡法分彆檢測心肌組織中Rho激酶mRNA和蛋白質的錶達.結果 正常對照組大鼠LVWI和TDM明顯低于SHR對照組[(2.98±0.05)比(3.16±0.08) mg/g、(18.18±0.75)比(21.32±1.25) μm,P＜0.01],而法舒地爾榦預各組大鼠LVWI和TDM明顯低于SHR對照組[SHRL組(3.12±0.05)mg/g、SHRM組(3.10±0.07) mg/g、SHRH組(3.08±0.09) mg/g、SHR對照組(3.16±0.08)mg/g,SHRL組(20.11±1.15) μm、SHRM組(19.63±1.62)μm、SHRH組(18.91±1.05) μm、SHR對照組(21.32±1.25) μm,P ＜0.01,P ＜0.05]；XBDP組分彆為[(3.14±0.08) mg/g、(21.42±1.23)μm,P＞0.05].與SHR對照組相比,法舒地爾榦預各組大鼠心肌組織中Rho激酶mRNA和蛋白質錶達明顯降低,隨劑量增加錶達下降[mRNA錶達:SHRL組(0 45±0.08)、SHRM組(0.37±0.07)、SHRH組(0.32±0.07)比SHR對照組(0.63±0.07),蛋白質錶達:SHRL組(0.78±0.11)、SHRM組(0.73±0.10)、SHRH組(0.68±0.10)、SHR對照組(0.90±0.10),P＜0.01,P＜0.05]；而XBDP組變化不明顯[mRNA錶達(0.56±0.07)、蛋白質錶達(0.85 ±0.10),P＞0.05].結論 Rho激酶抑製劑能夠抑製SHR左心室心肌肥厚,其機製可能與下調心肌組織中Rho激酶mRNA和蛋白質的錶達有關.
목적 연구Rho격매억제제법서지이대자발성고혈압대서(SHR)좌심실심기비후적영향.방법 30지SHR분위5조:SHR대조조；법서지이소제량조(SHRL)、중제량조(SHRM)、대제량조(SHRH)화초분지평조(XBDP),매조6지；6지Wistar-Kyoto대서위정상대조조.급약공8주,분별측량치료전후미동맥수축압(SBP)、좌심실중량지수(LVWI)、심기세포횡경(TDM).RT-PCR화Western인적법분별검측심기조직중Rho격매mRNA화단백질적표체.결과 정상대조조대서LVWI화TDM명현저우SHR대조조[(2.98±0.05)비(3.16±0.08) mg/g、(18.18±0.75)비(21.32±1.25) μm,P＜0.01],이법서지이간예각조대서LVWI화TDM명현저우SHR대조조[SHRL조(3.12±0.05)mg/g、SHRM조(3.10±0.07) mg/g、SHRH조(3.08±0.09) mg/g、SHR대조조(3.16±0.08)mg/g,SHRL조(20.11±1.15) μm、SHRM조(19.63±1.62)μm、SHRH조(18.91±1.05) μm、SHR대조조(21.32±1.25) μm,P ＜0.01,P ＜0.05]；XBDP조분별위[(3.14±0.08) mg/g、(21.42±1.23)μm,P＞0.05].여SHR대조조상비,법서지이간예각조대서심기조직중Rho격매mRNA화단백질표체명현강저,수제량증가표체하강[mRNA표체:SHRL조(0 45±0.08)、SHRM조(0.37±0.07)、SHRH조(0.32±0.07)비SHR대조조(0.63±0.07),단백질표체:SHRL조(0.78±0.11)、SHRM조(0.73±0.10)、SHRH조(0.68±0.10)、SHR대조조(0.90±0.10),P＜0.01,P＜0.05]；이XBDP조변화불명현[mRNA표체(0.56±0.07)、단백질표체(0.85 ±0.10),P＞0.05].결론 Rho격매억제제능구억제SHR좌심실심기비후,기궤제가능여하조심기조직중Rho격매mRNA화단백질적표체유관.
Objective To explore the effects of Rho-kinase inhibitor on cardiac hypertrophy of left ventricle in spontaneously hypertensive rats (SHR).Methods SHRs (n =30) were randomly divided into 5 groups (n =6 each):SHR control group,5 mg/kg fasudil group (SHRL),10 mg/kg fasudil group (SHRM),20 mg/kg fasudil group (SHRH) and nifedipine group (XBDP,10 mg/kg).Six male WistarKyoto rats were selected as normal control group (WKY group).Systolic blood pressure (SBP) was measured before and after treatment every 2 weeks.The hypertrophic parameters of left ventricular weight index (LVWI) and cardiomyocyte transverse diameter (TDM) were measured.In addition,the expression levels of Rho kinase mRNA and protein in cardiomyocytes were observed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.Results The levels of LVWI and TDM in WKY group were significantly lower than those in SHR control group [(2.98 ± 0.05) vs (3.16 ± 0.08) mg/g,(18.18 ±0.75)vs(21.32 ± 1.25) μm,P ＜ 0.01].After 8 weeks,the levels of LVWI and TDM in three fasudil groups were markedly lower than those in SHR control group [SHRL group:(3.12 ± 0.05) mg/g,SHRM group:(3.10±0.07) mg/g,SHRH group:(3.08 ±0.09) mg/g vs SHR control group:(3.16 ±0.08)mg/g,SHRL group:(20.11 ±1.15) μm,SHRM group:(19.63±1.62) μm,SHRH group:(18.91 ±1.05) μm vs SHR control group:(21.32 ± 1.25) μm,P ＜ 0.05 or P ＜ 0.01].But the levels of LVWI and TDM were not different between SHR control and XBDP groups [(3.14 ± 0.08) mg/g,(21.42 ±1.23) μm,P ＞ 0.05].Compared with SHR control group,the expression of Rho kinase mRNA and protein in cardiomyocytes significantly decreased in three fasudil groups [SHRL group mRNA:(0.45 ± 0.08),SHRM group mRNA:(0.37 ± 0.07),SHRH group mRNA:(0.32 ± 0.07) vs SHR control group mRNA:(0.63 ±0.07),SHRL group protein:0.78 ±0.11),SHRM group protein:(0.73 ±0.10),SHRH group protein:(0.68 ±0.10) vs SHR control group protein:(0.90 ± 0.1),P ＜0.05 or P ＜0.01],but showed no obvious change in XBDP group [mRNA:(0.56 ± 0.07),protein:(0.85 ± 0.10),P ＞ 0.05].Conclusions Rho kinase inhibitor may significantly down-regulate the expression of Rho kinase in cardiomyocytes of SHR.The mechanism is probably due to the favorable effects of Rho kinase inhibitor in the prevention of cardiac hypertrophy of left ventricle.
