当代医学
噹代醫學
당대의학
CHINA CONTEMPORARY MEDICINE
2013年
27期
1-2,3
,共3页
心肌纤维化%心肌重塑%Rho/Rock信号通路%卡维地洛
心肌纖維化%心肌重塑%Rho/Rock信號通路%卡維地洛
심기섬유화%심기중소%Rho/Rock신호통로%잡유지락
Myocardiac ifbrosis%Rho/Rock signaling pathway%Ventricular remodeling%Carvedilol
目的研究卡维地洛对异丙肾上腺素诱导大鼠心肌重塑中的作用及对Rho/Rock信号通路的影响。方法24只雄性SD大鼠随机分成3组：空白对照组(对照组)、ISO模型组（模型组）、卡维地洛（Carvedilol Car）组(治疗组)，每组8只。模型组和治疗组皮下多点注射ISO[5 mg/(kg·d)×10 d]建立大鼠心肌纤维化模型，其中治疗组给予Car[10 mg/(kg·d)]灌胃，模型组及对照组每日给予相同体积的生理盐水灌胃。6周后取左室心肌组织进行MASSON染色、免疫组织化学染色，分别检测胶原容积分数(CVF)、心肌组织中转化生长因子-β1（TGF-β1）表达量；RT-PCR法检测心肌组织RhoA和Rho激酶(Rock)mRNA的表达。结果与对照组比较，模型组大鼠CVF增加，TGF-β1表达增高(P＜0.01)，左室组织RhoA和Rho激酶mRNA表达上调(P＜0.01）；与模型组比较，治疗组CVF表达下降（P＜0.01），TGF-β1、RhoA和Rho激酶mRNA表达减少(P＜0.01），但均仍高于对照组（P＜0.01）。结论 ISO诱导心肌纤维化伴有Rho/Rock信号通路激活，卡维地洛能抑制Rho/Rock信号转导通路的活性、抑制TGF-β1表达，减轻心肌纤维化。
目的研究卡維地洛對異丙腎上腺素誘導大鼠心肌重塑中的作用及對Rho/Rock信號通路的影響。方法24隻雄性SD大鼠隨機分成3組：空白對照組(對照組)、ISO模型組（模型組）、卡維地洛（Carvedilol Car）組(治療組)，每組8隻。模型組和治療組皮下多點註射ISO[5 mg/(kg·d)×10 d]建立大鼠心肌纖維化模型，其中治療組給予Car[10 mg/(kg·d)]灌胃，模型組及對照組每日給予相同體積的生理鹽水灌胃。6週後取左室心肌組織進行MASSON染色、免疫組織化學染色，分彆檢測膠原容積分數(CVF)、心肌組織中轉化生長因子-β1（TGF-β1）錶達量；RT-PCR法檢測心肌組織RhoA和Rho激酶(Rock)mRNA的錶達。結果與對照組比較，模型組大鼠CVF增加，TGF-β1錶達增高(P＜0.01)，左室組織RhoA和Rho激酶mRNA錶達上調(P＜0.01）；與模型組比較，治療組CVF錶達下降（P＜0.01），TGF-β1、RhoA和Rho激酶mRNA錶達減少(P＜0.01），但均仍高于對照組（P＜0.01）。結論 ISO誘導心肌纖維化伴有Rho/Rock信號通路激活，卡維地洛能抑製Rho/Rock信號轉導通路的活性、抑製TGF-β1錶達，減輕心肌纖維化。
목적연구잡유지락대이병신상선소유도대서심기중소중적작용급대Rho/Rock신호통로적영향。방법24지웅성SD대서수궤분성3조：공백대조조(대조조)、ISO모형조（모형조）、잡유지락（Carvedilol Car）조(치료조)，매조8지。모형조화치료조피하다점주사ISO[5 mg/(kg·d)×10 d]건립대서심기섬유화모형，기중치료조급여Car[10 mg/(kg·d)]관위，모형조급대조조매일급여상동체적적생리염수관위。6주후취좌실심기조직진행MASSON염색、면역조직화학염색，분별검측효원용적분수(CVF)、심기조직중전화생장인자-β1（TGF-β1）표체량；RT-PCR법검측심기조직RhoA화Rho격매(Rock)mRNA적표체。결과여대조조비교，모형조대서CVF증가，TGF-β1표체증고(P＜0.01)，좌실조직RhoA화Rho격매mRNA표체상조(P＜0.01）；여모형조비교，치료조CVF표체하강（P＜0.01），TGF-β1、RhoA화Rho격매mRNA표체감소(P＜0.01），단균잉고우대조조（P＜0.01）。결론 ISO유도심기섬유화반유Rho/Rock신호통로격활，잡유지락능억제Rho/Rock신호전도통로적활성、억제TGF-β1표체，감경심기섬유화。
Objective To investigate the effect of Carvedilol on RhoA/Rock signaling pathway in cardiac ifbrosis induced by isoproterenol (ISO)in rats and its mechanisms.Methods Twenty four SD rats were randomly divided into control group, ISO model group and Carvedilol (Car)group(therapy group), 8 rats in each group. Cardiac ifbrosis models were induced by subcutaneous injection of ISO[5 mg/(kg·d)]except for control group. Meanwhile, Therapy group were administrated by Car[10 mg/(kg·d)], and rats in the other two groups were given equal saline. After 6 weeks, the cross serial transverse sections of left ventricle (LV) of the rats were examined microscopically for collagen volume fraction (CVF) and transforming growth factorβ1 (TGF-β1) protein using an image analysis computer system after Masson staining and TGF-β1-antibody immunohistochemistry(IHC) staining respectively. RhoA and Rho kinase mRNA were tested by RT-PCR.Results Compared with those of control group, the expression levels of the protein of TGF-β1 and RhoAmRNA and Rho kinase mRNA increased in ISO model group(P<0.01). However,CVF(P<0.01), the protein of TGF-β1, the expression levels of RhoA and Rho kinase mRNAwere lower in Therapy group than in ISO model group (P<0.01).There were some degree of improvements in all parameters. Conclusion Rho/Rho kinase signaling pathway may play an important role in myocardial ifbrosis induced by ISO, and carvedilol can improve the pathological changes , which is associated with the inhibition of RhoA/Rho kinase signaling pathway and down-regulation of TGF-β1 expression level.
