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Hydrogen sulfide preconditioning could ameliorate reperfusion associated injury in diabetic cardiomyopathy rat heart through preservation of mitochondria
Biochimie ( IF 3.9 ) Pub Date : 2019-01-22 , DOI: 10.1016/j.biochi.2019.01.011
Mahalakshmi Ansari , Gino A. Kurian

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.



中文翻译:

硫化氢预处理可通过保护线粒体减轻糖尿病性心肌病大鼠心脏的再灌注相关损伤

有证据表明,硫化氢预处理(HIPC)通过减轻线粒体中的自由基和钙超载,是治疗缺血再灌注(I / R)的有效方案。但是,HIPC的功效在接受I / R手术的糖尿病性心肌病(DCM)心脏中很大程度上未知。

将雄性Wistar大鼠随机分为三组:i)正常,ii)糖尿病(DM),和iii)糖尿病性心肌病(DCM)。通过在4周龄(35mg / kg,ip)使用链脲佐菌素注射来制备DM和DCM动物。DCM动物另外接受高脂饮食3个月。使用具有连续血流动力学监测的Langendorff装置灌注离体大鼠心脏。

与正常大鼠心脏相比,在再灌注后,DCM心脏的心脏生理效率受到很大损害(梗死面积高94%,相对压力积低65%)。HIPC有效地将受I / R攻击的正常大鼠心脏的心脏生理状况提高了62.5%(RPP),将伤害降低了60%(梗塞面积),随后将线粒体电子转运链酶活性NQR保留了57%,膜电位,肿胀行为,ATP与I / R相比降低了55%的脂质过氧化作用,从而降低了脂质含量,ATP的生产能力和氧化防御系统。但在DM和DCM动物中,用HIPC调节的离体心脏可显着改善DM的心脏生理(RPP)44%和DCM的58%,将DM和DCM的组织损伤(梗塞面积)分别抑制72%和79%,并保持线粒体仅在其自身的伪造控制下进行活动,主要是由于基底水平缺损。此外,我们发现,糖尿病心脏线粒体的SSM分数比HIPC的IFM表现出整体更好的功能改善。但是,线粒体经历的I / R相关的氧化应激并未通过HIPC改善。

更新日期:2019-01-22
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