Zhang Kai, Xu Xia, Hu Lihong
Department of Anesthesiology, Ningbo Medical Center Lihuili Hospital, Ningbo, China.
Ann Transl Med. 2022 Mar;10(6):350. doi: 10.21037/atm-22-115.
Sevoflurane can protect organs from ischemia-reperfusion (IR) injury, but the mechanism is still unclear. MicroRNA-122 (miR-122) is a liver-specific microRNA (miRNA) and regulates liver function. Therefore, this study aims to elucidate the relationship between the protective effect of sevoflurane and miR-122 in liver IR injury.
Wistar rats were divided into the following groups: sham, IR, IR + sevoflurane, IR + miR-122 antagomir, and IR + miR-122 antagomir + sevoflurane. Hematoxylin and eosin (H&E) staining and Suzuki score were used to evaluate the pathological damage of the liver. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 in the serum and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in the liver homogenate supernatant were detected by using the corresponding kit. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and flow cytometry was applied to evaluate the apoptosis of liver tissues. The expression of nuclear factor E2-related factor 2 (Nrf2), miR-122, p53, and HO-1 in liver tissue was evaluated by using immunohistochemistry, qRT-PCR, and western blot as needed.
Compared to the IR group, the sevoflurane post-treatment or miR-122 antagomir groups showed improved liver injury, decreased Suzuki score, inhibited the levels of AST, ALT, LDH, MDA, NO, TNF-α, IL-1β, and IL-6, increased levels of SOD, IL-10, and inhibited hepatocyte apoptosis. Regarding the molecular mechanism, sevoflurane post-treatment fostered the expression of HO-1, promoted the transport of Nrf2 from cytoplasm to the nucleus, and decreased the expression of miR-122 and p53. The combined use of miR-122 antagomir and sevoflurane enhanced the protective effect of miR-122 antagomir in liver injury in IR rats.
Sevoflurane protected the liver from IR damage by regulating the miR-122/Nrf2/HO-1 pathway.
七氟醚可保护器官免受缺血再灌注（IR）损伤，但其机制仍不清楚。微小RNA-122（miR-122）是一种肝脏特异性微小RNA（miRNA），并调节肝功能。因此，本研究旨在阐明七氟醚的保护作用与miR-122在肝脏IR损伤中的关系。
将Wistar大鼠分为以下几组：假手术组、IR组、IR + 七氟醚组、IR + miR-122拮抗剂组以及IR + miR-122拮抗剂 + 七氟醚组。采用苏木精-伊红（H&E）染色和铃木评分评估肝脏的病理损伤。使用相应试剂盒检测血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、乳酸脱氢酶（LDH）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6和IL-10的水平，以及肝匀浆上清液中丙二醛（MDA）、超氧化物歧化酶（SOD）和一氧化氮（NO）的水平。应用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）和流式细胞术评估肝组织的凋亡情况。根据需要，采用免疫组织化学、qRT-PCR和蛋白质免疫印迹法评估肝组织中核因子E2相关因子2（Nrf2）、miR-122、p53和血红素加氧酶-1（HO-1）的表达。
与IR组相比，七氟醚后处理组或miR-122拮抗剂组肝损伤改善，铃木评分降低，AST、ALT、LDH、MDA、NO、TNF-α、IL-1β和IL-6水平受到抑制，SOD、IL-10水平升高，肝细胞凋亡受到抑制。关于分子机制，七氟醚后处理促进HO-1的表达，促进Nrf2从细胞质向细胞核的转运，并降低miR-122和p53的表达。miR-122拮抗剂与七氟醚联合使用增强了miR-122拮抗剂对IR大鼠肝损伤的保护作用。
七氟醚通过调节miR-122/Nrf2/HO-1通路保护肝脏免受IR损伤。
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