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Protective effects of BiP inducer X (BIX) against diabetic cardiomyopathy in rats

机译:BIP诱导X(BIX)对大鼠糖尿病心肌病的保护作用

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Diabetic cardiomyopathy (DC) is associated with impaired endoplasmic reticulum (ER) function, development of ER stress, and induction of cardiac cell apoptosis. Preventive effects of BiP inducer X (BIX) were investigated against DC characteristic changes in a type 2 diabetes rat model. To establish diabetes, a high-fat diet and a single dose of streptozotocin were administered. Then, animals were assigned into the following groups: control, BIX, diabetic animals monitored for one, two, and three weeks. Diabetic rats were treated with BIX for one, two, and three weeks. Expressions of various ER stress and apoptotic markers were assessed by immunoblotting method. CHOP gene expression was assessed by Real-time PCR. Tissue expression of BiP was evaluated by immunohistochemistry method. Hematoxylin and eosin and Masson's trichrome staining were performed to assess histological changes in the left ventricle. Cardiac cell apoptosis was examined using TUNEL assay. BIX administration suppressed the activation of the ER stress markers and cleavage of procaspase-3 in the diabetic rats. Likewise, tissue expression of BiP protein was increased, while CHOP mRNA levels were decreased. These results were accompanied by reducing cardiac fibrosis and myocardial cell apoptosis suggesting protective effects of BIX against the development of DC by decreasing cardiomyocyte apoptosis and fibrosis.
机译:糖尿病心肌病(DC)与内质网(ER)功能受损、内质网应激的发展和心肌细胞凋亡的诱导有关。在2型糖尿病大鼠模型中,研究了BiP诱导剂X(BIX)对DC特性变化的预防作用。为了建立糖尿病,我们进行了高脂肪饮食和单剂量链脲佐菌素治疗。然后,将动物分为以下组:对照组、BIX组、糖尿病动物,分别监测一周、两周和三周。糖尿病大鼠分别用BIX治疗1周、2周和3周。免疫印迹法检测各种内质网应激和凋亡标志物的表达。实时荧光定量PCR检测CHOP基因的表达。免疫组织化学方法检测BiP的组织表达。苏木精、伊红和马森三色染色用于评估左心室的组织学变化。TUNEL法检测心肌细胞凋亡。BIX给药抑制糖尿病大鼠内质网应激标记物的激活和前蛋白酶-3的切割。同样,BiP蛋白的组织表达增加,而CHOP mRNA水平降低。这些结果伴随着心肌纤维化和心肌细胞凋亡的减少,表明BIX通过减少心肌细胞凋亡和纤维化而对DC的发展具有保护作用。

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