Department of Surgery, Istinye University, Faculty of Medicine, VM Mersin Medical Park Hospital, Mersin, Turkey.
Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):3088-3095. doi: 10.26355/eurrev_201904_17592.
Mammalian transient receptor potential melastatin (TRPM) channels are a form of calcium channels and they transport calcium and magnesium ions. TRPM has eight subclasses including TRPM1-8. TRPM2, TRPM6, TRPM7, TRPM8 are expressed especially in the liver cell. Therefore, we aim to investigate the effects of TRPM2, TRPM6, TRPM7, and TRPM8 gene expression and histopathologic changes after treatment of verapamil in the hepatic ischemia-reperfusion rat model.
Animals were randomly assigned to one or the other of the following groups including sham (n=8) group, verapamil (calcium entry blocker) (n=8) group, I/R group (n=8) and I/R- verapamil (n=8) group. TRPM 2, 6, 7, 8 gene expression level was were assessed by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and histopathologic changes were determined by the hematoxylin and eosin (HE) examination.
The expression level of TRPM 2, 6, 7, and 8 genes was were significantly higher in ischemia-reperfusion (I/R), verapamil, IR-verapamil groups compared to sham group. The p-values were 0.0024, < 0.0001, 0.0002, 0.006 for TRPM2, TRPM6, TRPM7, and TRPM8, respectively. Severe necrotic, degenerative differentiations and severe hemorrhagic areas were observed in hepatocytes from IR group. Also, moderate necrotic and degenerative differentiations and moderate hemorrhagic areas were observed in hepatocytes from IR-verapamil group.
This is the first study reporting an association between the expression level of TRPM 2, 6, 7, 8 in a hepatic ischemia-reperfusion rat model. Moreover, TRPM 2, 6, 7, 8 affect hepatic ischemia-reperfusion.
哺乳动物瞬时受体电位 melastatin(TRPM)通道是一种钙通道,它们运输钙和镁离子。TRPM 有 8 个亚类,包括 TRPM1-8。TRPM2、TRPM6、TRPM7、TRPM8 主要在肝细胞中表达。因此,我们旨在研究维拉帕米处理后肝缺血再灌注大鼠模型中 TRPM2、TRPM6、TRPM7 和 TRPM8 基因表达和组织病理学变化的影响。
动物随机分为以下几组:假手术(n=8)组、维拉帕米(钙通道阻滞剂)(n=8)组、缺血再灌注(I/R)组(n=8)和 I/R-维拉帕米(n=8)组。通过实时定量聚合酶链反应(RT-qPCR)评估 TRPM 2、6、7、8 基因表达水平,通过苏木精和伊红(HE)染色评估组织病理学变化。
缺血再灌注(I/R)、维拉帕米、IR-维拉帕米组 TRPM 2、6、7、8 基因表达水平均明显高于假手术组,P 值分别为 0.0024、<0.0001、0.0002、0.006。I/R 组肝细胞可见严重坏死、变性分化和严重出血区。IR-维拉帕米组肝细胞也可见中度坏死、变性分化和中度出血区。
这是第一项关于 TRPM 2、6、7、8 在肝缺血再灌注大鼠模型中表达水平的研究。此外,TRPM 2、6、7、8 影响肝缺血再灌注。