Hydrogen sulfide preconditioning could ameliorate reperfusion associated injury in diabetic cardiomyopathy rat heart through preservation of mitochondria
Hydrogen sulfide preconditioning could ameliorate reperfusion associated injury in diabetic cardiomyopathy rat heart through preservation of mitochondria
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DOI：
10.1016/j.biochi.2019.01.011
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发表时间：
2019-03-01
期刊：
影响因子：
3.9
通讯作者：
Kurian, Gino A.
中科院分区：
文献类型：
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作者：
Ansari, Mahalakshmi;Kurian, Gino A.
有证据表明，硫化氢预处理（HIPC）是一种有效的管理缺血再灌注（I/R）的协议，通过减轻自由基和线粒体钙超载。将雄性Wistar大鼠随机分为正常组、糖尿病组和糖尿病心肌病组。在4周龄时用链脲佐菌素（35 mg/kg，i.p）注射制备DM和DCM动物。DCM动物另外给予高脂肪饮食3个月。用Langendorff装置对离体大鼠心脏进行连续血流动力学监测，发现DCM心脏再灌注后，心脏生理效率明显低于正常心脏（梗死面积高94%，相对压积低65%）。与I/R相比，HIPC可有效地改善I/R大鼠心脏生理功能（RPP）62.5%，减轻心肌损伤60%（体积大小），并使线粒体电子传递链酶活性（NQR）、膜电位、肿胀行为、ATP含量、ATP产生能力和氧化防御系统的保护率提高57%，脂质过氧化反应降低55%。但在DM和DCM动物中，HIPC处理的离体心脏显著改善了DM和DCM的心脏生理学（RPP），分别为44%和58%，阻止了DM和DCM的组织损伤（心肌大小），仅保留了其自身假手术对照的线粒体活性，主要是由于基础水平缺陷。此外，我们发现，SSM部分糖尿病心脏线粒体显示整体更好地改善其功能比IFM的HIPC。然而，HIPC并不能改善I-R相关的氧化应激。(C)2019 Elsevier B. V.和法国生物化学与生物分子学会（SFBBM）。All rights reserved.
Evidence suggests that hydrogen sulfide precondition (HIPC) is an effective protocol in the management of ischemia reperfusion (I/R) by attenuating free radical and calcium overload in mitochondria. However the efficacy of HIPC is largely unknown in diabetic cardiomyopathy (DCM) hearts subjected to I/R procedure.Male Wistar rats were randomly divided into three groups: i) normal, ii) diabetes mellitus (DM), and iii) diabetic cardiomyopathy (DCM). DM and DCM animals were prepared by using streptozotocin injection at the age of 4 week (35 mg/kg, i.p). DCM animals were additionally administered with high fat diet for 3 months. Isolated rat hearts were perfused by using Langendorff apparatus with continuous hemodynamic monitoring.Following reperfusion, cardiac physiological efficiency was highly compromised in DCM heart (high infarct size by 94% and low relative pressure product by 65%) as compared to normal rat heart. HIPC effectively improved cardiac physiology of I/R challenged normal rat hearts by 62.5% (RPP), reduced injury by 60% (Infarct size) and subsequently preserved mitochondrial electron transport chain enzyme activities NQR by 57%, membrane potential, swelling behaviour, ATP content, ATP producing capacity and oxidative defence system by reducing lipid peroxidation by 55% compared with I/R. But in DM and DCM animals, isolated hearts conditioned with HIPC substantially improved cardiac physiology (RPP) by 44% in DM and 58% in DCM, arrest tissue injury (Infarct size) by 72% in DM and 79% in DCM and preserved mitochondrial activity only to its own sham control, primarily due to the basal level defect. Furthermore, we found that SSM fraction of diabetic heart mitochondria showed overall better improvement in their function than IFM by HIPC. However, mitochondrion experienced I/R associated oxidative stress was not improved by HIPC. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.