Department of Anaesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
Eur Rev Med Pharmacol Sci. 2021 Jan;25(2):968-975. doi: 10.26355/eurrev_202101_24666.
The aim of this study was to explore the effects of sevoflurane (SEV) pretreatment on Adriamycin (ADR)-induced myocardial injury through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway.
A total of 24 rats weighing 200-250 g were divided into four groups, including: control group (C group), ADR injection group (ADR group), SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group). H9c2 cells were cultured in vitro and were divided into control group (C group), ADR treatment group (ADR group), and SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group) as well. Next, the content of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the serum was detected via Enzyme-Linked Immunosorbent Assay (ELISA). Hematoxylin-eosin (HE) staining assay was performed to determine the severity of myocardial injury. Meanwhile, the apoptosis rate of cells was detected through terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Additionally, Western blotting (WB) was employed to measure the protein expression levels of phosphorylated (p)-GSK-3β, p-PI3K, Akt and p-Akt.
Compared with C group, ADR significantly increased the content of AST, LDH and CK in the serum (p<0.01), reduced protein expression levels of p-GSK-3β, p-PI3K and p-Akt (p<0.01), increased apoptosis rate (p<0.01), and induced myocardial injury. SEV pretreatment significantly alleviated the effect of ADR, manifested as significantly lowered content of AST, LDH and CK in the serum (p<0.01), distinctly elevated protein expression levels of p-GSK-3β, p-PI3K and p-Akt (p<0.01), notably reduced apoptosis rate (p<0.01), and relieved myocardial injury. LY294002 remarkably inhibited the protective effect of SEV against myocardial injury (p<0.01) CONCLUSIONS: SEV is able to prominently ameliorate ADR-induced myocardial injury by regulating the phosphorylation level of the PI3K/Akt/GSK-3β signaling pathway.
本研究旨在探讨七氟醚（SEV）预处理通过磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）/糖原合成酶激酶-3β（GSK-3β）通路对阿霉素（ADR）诱导的心肌损伤的影响。
将 24 只体重 200-250 g 的大鼠分为四组：对照组（C 组）、ADR 注射组（ADR 组）、SEV 预处理组（ADR+SEV 组）和抑制剂组（ADR+SEV+LY 组）。体外培养 H9c2 细胞，分为对照组（C 组）、ADR 处理组（ADR 组）、SEV 预处理组（ADR+SEV 组）和抑制剂组（ADR+SEV+LY 组）。然后通过酶联免疫吸附试验（ELISA）检测血清中天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）和肌酸激酶（CK）的含量。通过苏木精-伊红（HE）染色法测定心肌损伤程度。同时，通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记（TUNEL）检测细胞凋亡率。此外，采用 Western blot（WB）法测定磷酸化（p）-GSK-3β、p-PI3K、Akt 和 p-Akt 的蛋白表达水平。
与 C 组相比，ADR 显著增加了血清中 AST、LDH 和 CK 的含量（p<0.01），降低了 p-GSK-3β、p-PI3K 和 p-Akt 的蛋白表达水平（p<0.01），增加了细胞凋亡率（p<0.01），并诱导了心肌损伤。SEV 预处理显著减轻了 ADR 的作用，表现为血清中 AST、LDH 和 CK 的含量明显降低（p<0.01），p-GSK-3β、p-PI3K 和 p-Akt 的蛋白表达水平明显升高（p<0.01），细胞凋亡率明显降低（p<0.01），心肌损伤减轻。LY294002 显著抑制了 SEV 对心肌损伤的保护作用（p<0.01）。
SEV 通过调节 PI3K/Akt/GSK-3β 信号通路的磷酸化水平，显著改善 ADR 诱导的心肌损伤。
