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|本期目录/Table of Contents|

木犀草素减轻糖尿病小鼠心肌损伤及其机制

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第1期
页码:
30-034,039
栏目:
基础研究
出版日期:
2017-10-10

文章信息/Info

Title:
Effects of luteolin on myocardial injury and underlying mechanisms in diabetic mice
作者:
王 雷1; 孙书红2; 3; 付爱萍4; 王 曼1; 谢芳元1
(1.西安市第四医院心内科 陕西 西安 710004；2.武警陕西总队医院心内科 陕西 西安 710054；3.第四军医大学西京医院心内科 陕西 西安 710032；4.陕西航天医院内分泌科 陕西 西安 710025)
Author(s):
WANG Lei1;  SUN Shu-hong2; 3;  FU Ai-ping4;  WANG Man1;  XIE Fang-yuan1
(1.Department of Cardiology, Fourth Hospital of Xi’an, Xi’an 710004, Shaanxi, China; 2.Department of Cardiology, Hospital of Shaanxi Armed Police Corps, Xi’an 710054, Shaanxi, China; 3.Department of Cardiology, Xijing Hospital, Fourth Military Medical Uni
关键词:
木犀草素; 糖尿病心肌病; 凋亡; Rho/ROCK2信号通路
Keywords:
luteolin;  diabetic cardiomyopathy;  apoptosis;  RhoA/ROCK2 signaling
分类号:
R284.1
DOI:
-
文献标识码:
A
摘要:
目的 探讨木犀草素（Luteolin,LTL）对糖尿病小鼠心肌损伤影响及其可能调控机制。方法 腹腔注射链脲霉素制备1型糖尿病小鼠模型，将雄性C57/BL6J小鼠分为3组（每组16只）：对照组，糖尿病组，糖尿病+木犀草素组。糖尿病+木犀草素组给予LTL 50 mg/（kg·d）灌胃，对照组和糖尿病组给予50 g/L的羧甲基纤维素钠灌胃。药物治疗3月后，小鼠心脏超声检测心功能；Masson评估胶原容积分数（collagen volume fraction，CVF)；Tunel法检测心肌细胞凋亡；Western blot检测Rho和ROCK2的表达。结果 与对照组相比，糖尿病组各项心功能指标显著降低（P<0.05），CVF显著增高（P<0.05），小鼠心肌细胞凋亡显著增高（P<0.05），Rho和ROCK2的表达显著增加（P<0.05）；与糖尿病组相比，糖尿病+木犀草素组各项心功能指标明显改善（P<0.05），CVF显著降低（P<0.05），小鼠心肌细胞凋亡显著降低（P<0.05），Rho和ROCK2的表达降低（P<0.05）。结论 LTL可能通过抑制RhoA/ROCK2信号通路减少糖尿病小鼠心肌细胞凋亡，从而减轻糖尿病心肌损伤。
Abstract:
AIM To explore the effects and mechanisms of luteolin on heart impairment in diabetic mice. METHODS Diabetes was induced by a single intraperitoneal of streptozotocin. Male C57/BL6J mice were randomly divided into three groups (n=16): control, diabetes, diabetes+luteolin. The diabetes+luteolin group were given a dose of 50 mg/(kg·d) of luteolin, while the control and diabetes groups received 50 g/L sodium carboxymethyl cellulose gavage. For 3 months, echocardiography was employed to evaluate cardiac function. Collagen volume fraction (CVF) was measured by masson staining and apoptotic index was examined by Tunel. Western blot was used to determine the expression of Rho and ROCK2. RESULTS Compared with the control group, cardiac function attenuated significantly (P<0.05), with increased CVF (P<0.05). There was enhanced apoptotic index (P<0.05) and expression of Rho and ROCK2 were upregulated (P<0.05) when compared to the control group. Compared with those in the diabetes group, the cardiac function was significantly improved (P<0.05) and CVF significantly diminished (P<0.05). There was a restored apoptotic index (P<0.05), and there was reduction of Rho and ROCK2 levels (P<0.05) by treatment with luteolin in the diabetes+luteolin group. CONCLUSION Luteolin significantly decreases the apoptotic index and protects against myocardial injury in diabetic mice, possibly by inhibiting activation of RhoA/ROCK2 signaling.

参考文献/References

[1]Bugger H,Bode C.The vulnerable myocardium.Diabetic cardiomyopathy[J].Hamostaseologie,2015,35(1):17-24.

[2]Falcao-Pires I,Leite-Moreira AF.Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment[J].Heart Fail Rev,2012,17(3):325-344.

[3]Holscher ME,Bode C,Bugger H.Diabetic Cardiomyopathy:Does the Type of Diabetes Matter?[J].Int J Mol Sci,2016,17(12).

[4]Wang D,Luo P,Wang Y,et al.Glucagon-like peptide-1 protects against cardiac microvascular injury in diabetes via a cAMP/PKA/Rho-dependent mechanism[J].Diabetes,2013,62(5):1697-1708.

[5]Kamijo H,Matsumura Y,Thumkeo D,et al.Impaired vascular remodeling in the yolk sac of embryos deficient in ROCK-I and ROCK-II[J].Genes Cells,2011,16(10):1012-1021.

[6]Nakagawa O,Fujisawa K,Ishizaki T,et al.ROCK-I and ROCK-II,two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice[J].FEBS Lett,1996,392(2):189-193.

[7]Koch JC,Tonges L,Barski E,et al.ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS[J].Cell Death Dis,2014,5:e1225.

[8]Pearson JT,Jenkins MJ,Edgley AJ,et al.Acute Rho-kinase inhibition improves coronary dysfunction in vivo, in the early diabetic microcirculation[J].Cardiovasc Diabetol,2013,12:111.

[9]Wu X,Xu T,Li D,et al.ERK/PP1a/PLB/SERCA2a and JNK pathways are involved in luteolin-mediated protection of rat hearts and cardiomyocytes following ischemia/reperfusion[J].PLoS One,2013,8(12):e82957.

[10]Bian C,Xu T,Zhu H,et al.Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p[J].PLoS One,2015,10(12):e144877.

[11]Fang F,Li D,Pan H,et al.Luteolin inhibits apoptosis and improves cardiomyocyte contractile function through the PI3K/Akt pathway in simulated ischemia/reperfusion[J].Pharmacology,2011,88(3-4):149-158.

[12]Middleton EJ,Kandaswami C,Theoharides TC.The effects of plant flavonoids on mammalian cells:implications for inflammation,heart disease,and cancer[J].Pharmacol Rev,2000,52(4):673-751.

[13]Jarosz J,Ghosh S,Delbridge LM,et al.Changes in mitochondrial morphology and organisation can enhance energy supply from mitochondrial oxidative phosphorylation in diabetic cardiomyopathy[J].Am J Physiol Cell Physiol,2017,312(2):C190-C197.

[14]Huynh K,Bernardo BC,Mcmullen JR,et al.Diabetic cardiomyopathy:mechanisms and new treatment strategies targeting antioxidant signaling pathways[J].Pharmacol Ther,2014,142(3):375-415.

[15]Khullar M,Al-Shudiefat AA,Ludke A,et al.Oxidative stress:a key contributor to diabetic cardiomyopathy[J].Can J Physiol Pharmacol,2010,88(3):233-240.

[16]Wang G,Li W,Lu X,et al.Luteolin ameliorates cardiac failure in type I diabetic cardiomyopathy[J].J Diabetes Complications,2012,26(4):259-265.

[17]Bando YK,Murohara T.Diabetes-related heart failure[J].Circ J,2014,78(3):576-583.

[18]Boudina S,Abel ED.Diabetic cardiomyopathy revisited[J].Circulation,2007,115(25):3213-3223.

[19]Baraka A,Abdelgawad H.Targeting apoptosis in the heart of streptozotocin-induced diabetic rats[J].J Cardiovasc Pharmacol Ther,2010,15(2):175-181.

[20]Miao L,Calvert JW,Tang J,et al.Upregulation of small GTPase RhoA in the basilar artery from diabetic(mellitus)rats[J].Life Sci,2002,71(10):1175-1185.

[21]Kacimi R,Gerdes AM.Alterations in G protein and MAP kinase signaling pathways during cardiac remodeling in hypertension and heart failure[J].Hypertension,2003,41(4):968-977.

[22]Hattori T,Shimokawa H,Higashi M,et al.Long-term inhibition of Rho-kinase suppresses left ventricular remodeling after myocardial infarction in mice[J].Circulation,2004,109(18):2234-2239.

[23]Chang J,Xie M,Shah VR,et al.Activation of Rho-associated coiled-coil protein kinase 1(ROCK-1)by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis[J].Proc Natl Acad Sci U S A,2006,103(39):14495-14500.

[24]Del Re DP,Miyamoto S,Brown JH.RhoA/Rho kinase up-regulate Bax to activate a mitochondrial death pathway and induce cardiomyocyte apoptosis[J].J Biol Chem,2007,282(11):8069-8078.

备注/Memo

备注/Memo:
收稿日期：2017-01-10.通讯作者：谢芳元，主任医师，主要从事冠心病的防治研究 Email：xiefangyuan2004007@126.com 作者简介：王雷，主治医师，硕士 Email：497552148@qq.com
更新日期/Last Update: 1900-01-01