Flos Puerariae extract prevents myocardial apoptosis via attenuation oxidative stress in streptozotocin-induced diabetic mice.
Flos Puerariae extract prevents myocardial apoptosis via attenuation oxidative stress in streptozotocin-induced diabetic mice.
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葛花提取物通过减弱链脲佐菌素诱导的糖尿病小鼠的氧化应激来防止心肌细胞凋亡。
DOI：
10.1371/journal.pone.0098044
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Yu W;Zha W;Guo S;Cheng H;Wu J;Liu C
糖尿病性心肌病（DCM）提示心肌细胞直接受损。细胞凋亡被认为是扩张型心肌病的标志之一。氧化应激在扩张型心肌病的发病机制中起关键作用。本研究探讨红花粗提物（FPE）对实验性糖尿病小鼠心肌细胞凋亡的预防作用。采用链脲佐菌素（STZ）50 mg/kg/d连续5 d腹腔注射诱导C57 BL/6 J小鼠实验性糖尿病模型。FPE（100、200 mg/kg）灌胃给药，每日1次，连续10周。在小鼠心脏中评估心脏结构变化、细胞凋亡、超氧化物产生、NADPH氧化酶亚基（gp 91 phox、p47 phox和p67 phox）表达以及相关调节因子。糖尿病小鼠表现为高血糖（≥11.1 mmol/L）和体重减轻。实验结束时，发现糖尿病小鼠的肌丝结构异常，以及TUNEL阳性的心肌细胞与Bax/Bcl-2比值增加和Caspase-3表达增加。此外，糖尿病小鼠心肌组织中ROS生成、NADP+/NADPH比值、NADPH氧化酶亚基gp 91 phox和p47 phox表达、脂质过氧化水平显著升高，抗氧化酶SOD和GSH-Px活性降低。相比之下，用FPE治疗导致正常化的葡萄糖和体重曲线。FPE给药还保护了糖尿病小鼠的心肌结构，减少了心肌细胞凋亡。氧化应激标志物的升高被FPE补充剂显著逆转。此外，FPE治疗显著抑制糖尿病小鼠心脏中Bax/Bcl-2比值和Caspase-3表达的增加，以及抑制JNK和P38 MAPK的活化。我们的数据首次表明，FPE可能具有治疗STZ诱导的糖尿病性心肌病的潜力，通过减少氧化应激，防止心肌细胞凋亡。这种作用可能是通过JNK和P38 MAPK信号通路介导的。
Diabetic cardiomyopathy (DCM) suggests a direct cellular insult to myocardium. Apoptosis is considered as one of the hallmarks of DCM. Oxidative stress plays a key role in the pathogenesis of DCM. In this study, we explored the prevention of myocardial apoptosis by crude extract from Flos Puerariae (FPE) in experimental diabetic mice. Experimental diabetic model was induced by intraperitoneally injection of streptozotocin (STZ, 50 mg/kg/day) for five consecutive days in C57BL/6J mice. FPE (100, 200 mg/kg) was orally administrated once a day for ten weeks. Cardiac structure changes, apoptosis, superoxide production, NADPH oxidase subunits expression (gp91phox, p47phox, and p67phox), and related regulatory factors were assessed in the heart of mice. Diabetic mice were characterized by high blood glucose (≥11.1 mmol/L) and reduced body weight. In the end of the experiment, aberrant myofilament structure, as well as TUNEL positive cardiac cells coupled with increased Bax/Bcl-2 ratio and Caspase-3 expression was found in diabetic mice. Moreover, ROS formation, the ratio of NADP+/NADPH and NADPH oxidase subunits expression of gp91phox and p47phox, lipid peroxidation level was significantly increased, while antioxidant enzyme SOD and GSH-Px activity were reduced in the myocardial tissue of diabetic mice. In contrast, treatment with FPE resulted in a normalized glucose and weight profile. FPE administration also preserved myocardial structure and reduced apoptotic cardiac cell death in diabetic mice. The elevated markers of oxidative stress were significantly reversed by FPE supplementation. Further, FPE treatment markedly inhibited the increased Bax/Bcl-2 ratio and Caspase-3 expression, as well as suppressed JNK and P38 MAPK activation in the heart of diabetic mice. Our data demonstrate for the first time that FPE may have therapeutic potential for STZ-induced diabetic cardiomyopathy through preventing myocardial apoptosis via attenuation oxidative stress. And this effect is probably mediated by JNK and P38 MAPK signaling pathway.
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DOI：
10.2147/dmso.s30968
发表时间：
2013
期刊：
Diabetes, metabolic syndrome and obesity : targets and therapy
影响因子：
--
作者：
Chavali V;Tyagi SC;Mishra PK
通讯作者：
Mishra PK
影响因子：
1.7
作者：
Maisch, B.;Alter, P.;Pankuweit, S.
通讯作者：
Pankuweit, S.
影响因子：
5.7
作者：
Berry, C.;Brett, M.;Norrie, J.
通讯作者：
Norrie, J.
影响因子：
37.8
作者：
Ho, FM;Liu, SH;Lin-Shiau, SY
通讯作者：
Lin-Shiau, SY
影响因子：
7.7
作者：
Nakagami, H;Morishita, R;Ogihara, T
通讯作者：
Ogihara, T