中国中医科学院广安门医院
纸质出版:2020
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[1]刘甜甜,王擎擎,姚魁武.活血温通方对心肌缺血模型大鼠心肌组织Sirt1信号通路的影响[J].中医杂志,2020,61(09):804-809.
LIU Tiantian, WANG Qingqing, YAO Kuiwu. Effects of Huoxue Wentong Formula (活血温通方) on Sirt1 Signaling Pathway in Myocardial Tissue of Myocardial Ischemia Model Rats[J]. Journal of Traditional Chinese Medicine2020, 61(9): 804-809.
[1]刘甜甜,王擎擎,姚魁武.活血温通方对心肌缺血模型大鼠心肌组织Sirt1信号通路的影响[J].中医杂志,2020,61(09):804-809. DOI: 10.13288/j.11-2166/r.2020.09.017.
LIU Tiantian, WANG Qingqing, YAO Kuiwu. Effects of Huoxue Wentong Formula (活血温通方) on Sirt1 Signaling Pathway in Myocardial Tissue of Myocardial Ischemia Model Rats[J]. Journal of Traditional Chinese Medicine2020, 61(9): 804-809. DOI: 10.13288/j.11-2166/r.2020.09.017.
目的探讨活血温通方对心肌缺血的影响及可能作用机制。方法雄性SD大鼠随机分为假手术组、模型组、阳性药组和活血温通方低、中、高剂量组
每组8只。除假手术组外其余各组采用结扎冠状动脉左前降支制备心肌缺血模型。造模后阳性药组灌胃单硝酸异山梨酯缓释片6.3mg/(kg·d)
活血温通方低、中、高剂量组分别灌胃活血温通方0.42、0.84、1.68g/(kg·d)
假手术组和模型组灌胃等体积蒸馏水。连续灌胃4周后检测血清心肌肌钙蛋白I(cTn-I)、肌酸激酶MB同工酶(CK-MB)、乳酸脱氢酶(LDH)含量
HE染色观察心脏结构
Masson染色观察心肌纤维化情况
Western blot法测定心脏沉默信息调节因子1(Sirt1)、核因子κB(NF-κB)、叉头蛋白盒子1(Foxo1)、p53蛋白表达变化。结果与假手术组比较
模型组大鼠血清cTn-I、CK-MB、LDH含量均明显升高(P<0.01)
缺血心脏肌间隙增大
肌纤维排列紊乱
出现大量炎性细胞浸润
同时胶原纤维化严重
Sirt1蛋白表达显著降低
NF-κB、Foxo1、p53蛋白表达增多(P<0.01)。与模型组比较
阳性药组和活血温通方中剂量组均可不同程度改善上述指标(P<0.05或P<0.01)
且活血温通方中剂量组在降低NF-κB及p53蛋白表达
升高Sirt1表达优于活血温通方低剂量组(P<0.01)
在降低CK-MB、LDH含量及NF-κB、Foxo1、p53蛋白表达亦优于活血温通方高剂量组(P<0.05或P<0.01)。活血温通方中剂量组在改善心脏病理效果亦佳。结论活血温通方可能通过上调Sirt1信号通路
逆转缺血心脏病理改变
从而改善心肌缺血损伤
以中剂量效果最好。
Objective To explore effects of Huoxue Wentong Formula(活血温通方) on myocardial ischemia and its possible mechanism. Methods Male SD rats were randomly divided into sham operation group
model group
positive medicine group
as well as Huoxue Wentong Formula low
medium
and high dose groups
with 8 rats in each group. For all groups but the sham operation group
left anterior descending coronary arteries were ligated to prepare models of myocardial ischemia. After modeling
the positive medicine group was administrated with 6.3 mg/(kg·d) isosorbide mononitrate sustained release tablets
the Huoxue Wentong Formula low
medium and high dose groups were administrated with 0.42
0.84 and 1.68 g/(kg·d) Huoxue Wentong Formula respectively
the sham operation group and the model group were given equal volume of distilled water by gavage. Serum cardiac troponin I(cTn-I)
creatine kinase MB isoenzyme(CK-MB) and lactate dehydrogenase(LDH) levels were measured 4 weeks after continuous gavage. Cardiac structure was observed by HE staining
and Masson staining was applied for observing on myocardial fibrosis. Western blot was used for determining expressions of cardiac silent information regulator 1(Sirt1)
nuclear factor κB(NF-κB)
forkhead box protein O1(Foxo1) and p53 protein. Results Compared with the sham operation group
the serum levels of cTn-I
CK-MB and LDH in the model group were significantly increased(P<0.01). Ischemic myocardium space was increased
muscle fibers were arranged disorderly
and infiltration of a large number of inflammatory cells occurred. At the same time
collagen fibrosis was severe
the Sirt1 protein expression was significantly decreased
and the NF-κB
Foxo1 and p53 protein expressions were increased(P<0.01). Compared with the model group
the above indexes could be improved to different degrees in the positive medicine group and the medium dose Huoxue Wentong Formula group(P<0.05 or P<0.01). The decrease of NF-κB and p53 protein expressions and the increase of Sirt1 expression in the medium dose Huoxue Wentong Formula group were more significant than those in the low dose Huoxue Wentong Formula group(P<0.01). And it was also better than the high dose Huoxue Wentong Formula group in decreasing CK-MB and LDH levels
as well as expressions of NF-κB
Foxo1 and p53 protein(P<0.05 or P<0.01). It was also effective in improving cardiac pathology in the medium dose Huoxue Wentong Formula group. Conclusion Huoxue Wentong Formula may reverse pathological changes of ischemic heart by up-regulating Sirt1 signaling pathway
thereby improving myocardial ischemic injury
and the efficacy is best at medium dose.
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