参芪扶正注射液对心力衰竭大鼠心室重塑的作用研究
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摘要
目的:
通过观察参芪扶正注射液对阿霉素(Adriamycin,ADR)诱导的心力衰竭大鼠心室重塑的影响,探讨其作用机制,为临床运用提供科学依据。
方法:
利用阿霉素的心脏毒性,诱导心力衰竭大鼠模型。雄性SD大鼠60只,随机平均分成6组:正常组、阿霉素模型组、卡托普利组、参芪扶正注射液(以下简称参芪)小剂量组、参芪扶正注射液中剂量组、参芪扶正注射液大剂量组。实验过程中观察大鼠的精神、活动、进食等情况,治疗8周后测定大鼠左室肥厚指数、HE染色观察心肌心肌病理变化、免疫组化观察心肌Ⅰ、Ⅲ胶原蛋白表达情况,RT-PCR法对心肌MMP-3、TIMP-1mRNA半定量分析。
结果:
1、心功能测定:模型组心功能(±dp/dtmax)明显低于正常组(P<0.01);与模型组相比,各药物治疗组可不同程度地改善心功能情况:其中,参芪中剂量组疗效显著(P<0.01),参芪大剂量组未见显著性改变(P>0.05)。
2、心肌肥厚指数:心衰模型组心体比及左室肥厚指数均明显高于正常组(P<0.01);与模型组相比,各药物治疗组可不同程度地改善心肌肥厚情况:其中,参芪中剂量组疗效显著(P<0.01),参芪大剂量组未见显著性改变(P>0.05)。
3、Ⅰ型、Ⅲ胶原蛋白表达:免疫组化染色结果显示,模型组Ⅰ、Ⅲ胶原蛋白表达明显高于正常组(P<0.01);与模型组比较,各药物治疗组可不同程度地减少胶原表达,其中参芪中剂量组Ⅰ、Ⅲ胶原表达显著下降(P<0.01),参芪大剂量组未有显著性差异(P>0.05)。
4、RT-PCR结果显示:与正常组相比,模型组MMP-3mRNA显著增高(P<0.01), TIMP-1mRNA显著降低(P<0.01);参芪小剂量、中剂量及卡托普利组MMP-3mRNA表达显著低于模型组(P<0.01, P<0.05);TIMP-1mRNA显著高于模型组(P<0.01,P<0.05);参芪大剂量组MMP-3mRNA、TIMP-1mRNA表达与模型组没有显著性差异(P>0.05)。
结论:
1、参芪扶正注射液能改善心功能情况。
2、参芪扶正注射液能减轻心力衰竭左室肥厚情况。
3、参芪扶正注射液能改善心肌Ⅰ、Ⅲ胶原蛋白表达情况。
4、参芪扶正注射液可减少MMP-3表达或抑制其活性,上调TIMP-1的表达。
Objective
To investigate the effects of Shenqi injection on ventricular remodeling and cardiac function of congestive heart failure rats induced by Adriamycin, which to provide evidence for clinic.
Methods:
Utilizing cardiac toxicity of Adriamycin to make the model of congestive heart failure rats. Sixty male SD rats were divided randomly into normal group, adriamycin model group, captopril group, Shenqi injection(short by Shenqi following) low dose group, Shenqi middle dose group, Shenqi large dose group. The spirits, activities, eatings were observed during the lab proc. Eight weeks later, we determined rat left ventricle heart indexs, pathological changes of cardiac muscle by HE dyeing, expressions of collagen proteinⅠ、Ⅲin cardiac muscle by immunity class, semiquantitative analysis of MMP-3, TIMP-1mRNA in cardiac muscle by RT-PCR methods.
Results:
1. Cardiac function determination: the cardiac function of model group were lower than the normal group (P<0.01). Compared with model group, each drug treatment group could improve cardiac function in different degree. Among these groups, the curative effect of Shenqi middle dose group was significant(P<0.01), the curative effect of Shenqi large dose group was unknown significance(P>0.05).
2. Myocardial hypertrophy index: the index and heart form of model group were highed than the normal group(P<0.01). Compared with model group, each drug treatment group could improve myocardial hypertrophy in different degree. Among these groups, the curative effect of Shenqi middle dose group was significant(P<0.01), the curative effect of Shenqi large dose group was unknown significance(P>0.05).
3. The expression of collagen proteinⅠ、Ⅲ: the results of immunity class dyeing showed that the expression of collagen proteinⅠ、Ⅲin group model group were all obviously higher than normal group(P<0.01);compared with model group, each drug treatment group could decrease the expression of collagen protein. Among these, the expression of Shenqi middle dosage group were significantly decreased(P<0.01), the expression of Shenqi large dosage group were unknown significant difference(P>0.05).
4. The results of RT-PCR:compared with normal group, MMP-3mRNA of model group were significant increased(P<0.01). TIMP-1mRNA of above group were significant decreased(P<0.01).The expression of MMP-3mRNA in small and middle dosage group and captopril group were significant lowed than the model group(P<0.01, P<0.05).The expression of TIMP-1mRNA in above group were significant highed than the model group(P<0.01, P<0.05). The expression of MMP-3mRNA、TIMP-1mRNA in large dosage showd no significant difference(P>0.05).
Conclusion:
1. Shenqi injection can improve the cardiac function.
2. Shenqi injection can lessen the pachynsis of left ventricle in congestive heart failure rats.
3. Shenqi injection Can improve the expression of collagen proteinⅠ、Ⅲ.
4. Shenqi injection can decreased the expression of MMP-3 or inhibit its activity, and increased the expression of TIMP-1.
通过观察参芪扶正注射液对阿霉素(Adriamycin,ADR)诱导的心力衰竭大鼠心室重塑的影响,探讨其作用机制,为临床运用提供科学依据。
方法:
利用阿霉素的心脏毒性,诱导心力衰竭大鼠模型。雄性SD大鼠60只,随机平均分成6组:正常组、阿霉素模型组、卡托普利组、参芪扶正注射液(以下简称参芪)小剂量组、参芪扶正注射液中剂量组、参芪扶正注射液大剂量组。实验过程中观察大鼠的精神、活动、进食等情况,治疗8周后测定大鼠左室肥厚指数、HE染色观察心肌心肌病理变化、免疫组化观察心肌Ⅰ、Ⅲ胶原蛋白表达情况,RT-PCR法对心肌MMP-3、TIMP-1mRNA半定量分析。
结果:
1、心功能测定:模型组心功能(±dp/dtmax)明显低于正常组(P<0.01);与模型组相比,各药物治疗组可不同程度地改善心功能情况:其中,参芪中剂量组疗效显著(P<0.01),参芪大剂量组未见显著性改变(P>0.05)。
2、心肌肥厚指数:心衰模型组心体比及左室肥厚指数均明显高于正常组(P<0.01);与模型组相比,各药物治疗组可不同程度地改善心肌肥厚情况:其中,参芪中剂量组疗效显著(P<0.01),参芪大剂量组未见显著性改变(P>0.05)。
3、Ⅰ型、Ⅲ胶原蛋白表达:免疫组化染色结果显示,模型组Ⅰ、Ⅲ胶原蛋白表达明显高于正常组(P<0.01);与模型组比较,各药物治疗组可不同程度地减少胶原表达,其中参芪中剂量组Ⅰ、Ⅲ胶原表达显著下降(P<0.01),参芪大剂量组未有显著性差异(P>0.05)。
4、RT-PCR结果显示:与正常组相比,模型组MMP-3mRNA显著增高(P<0.01), TIMP-1mRNA显著降低(P<0.01);参芪小剂量、中剂量及卡托普利组MMP-3mRNA表达显著低于模型组(P<0.01, P<0.05);TIMP-1mRNA显著高于模型组(P<0.01,P<0.05);参芪大剂量组MMP-3mRNA、TIMP-1mRNA表达与模型组没有显著性差异(P>0.05)。
结论:
1、参芪扶正注射液能改善心功能情况。
2、参芪扶正注射液能减轻心力衰竭左室肥厚情况。
3、参芪扶正注射液能改善心肌Ⅰ、Ⅲ胶原蛋白表达情况。
4、参芪扶正注射液可减少MMP-3表达或抑制其活性,上调TIMP-1的表达。
Objective
To investigate the effects of Shenqi injection on ventricular remodeling and cardiac function of congestive heart failure rats induced by Adriamycin, which to provide evidence for clinic.
Methods:
Utilizing cardiac toxicity of Adriamycin to make the model of congestive heart failure rats. Sixty male SD rats were divided randomly into normal group, adriamycin model group, captopril group, Shenqi injection(short by Shenqi following) low dose group, Shenqi middle dose group, Shenqi large dose group. The spirits, activities, eatings were observed during the lab proc. Eight weeks later, we determined rat left ventricle heart indexs, pathological changes of cardiac muscle by HE dyeing, expressions of collagen proteinⅠ、Ⅲin cardiac muscle by immunity class, semiquantitative analysis of MMP-3, TIMP-1mRNA in cardiac muscle by RT-PCR methods.
Results:
1. Cardiac function determination: the cardiac function of model group were lower than the normal group (P<0.01). Compared with model group, each drug treatment group could improve cardiac function in different degree. Among these groups, the curative effect of Shenqi middle dose group was significant(P<0.01), the curative effect of Shenqi large dose group was unknown significance(P>0.05).
2. Myocardial hypertrophy index: the index and heart form of model group were highed than the normal group(P<0.01). Compared with model group, each drug treatment group could improve myocardial hypertrophy in different degree. Among these groups, the curative effect of Shenqi middle dose group was significant(P<0.01), the curative effect of Shenqi large dose group was unknown significance(P>0.05).
3. The expression of collagen proteinⅠ、Ⅲ: the results of immunity class dyeing showed that the expression of collagen proteinⅠ、Ⅲin group model group were all obviously higher than normal group(P<0.01);compared with model group, each drug treatment group could decrease the expression of collagen protein. Among these, the expression of Shenqi middle dosage group were significantly decreased(P<0.01), the expression of Shenqi large dosage group were unknown significant difference(P>0.05).
4. The results of RT-PCR:compared with normal group, MMP-3mRNA of model group were significant increased(P<0.01). TIMP-1mRNA of above group were significant decreased(P<0.01).The expression of MMP-3mRNA in small and middle dosage group and captopril group were significant lowed than the model group(P<0.01, P<0.05).The expression of TIMP-1mRNA in above group were significant highed than the model group(P<0.01, P<0.05). The expression of MMP-3mRNA、TIMP-1mRNA in large dosage showd no significant difference(P>0.05).
Conclusion:
1. Shenqi injection can improve the cardiac function.
2. Shenqi injection can lessen the pachynsis of left ventricle in congestive heart failure rats.
3. Shenqi injection Can improve the expression of collagen proteinⅠ、Ⅲ.
4. Shenqi injection can decreased the expression of MMP-3 or inhibit its activity, and increased the expression of TIMP-1.
引文
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