Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Harbin, 150001, China.
Department of Tumor Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Harbin, 150001, China.
Inflammation. 2021 Aug;44(4):1288-1301. doi: 10.1007/s10753-021-01416-z. Epub 2021 Jan 26.
Propofol (PRO) protects against hepatic ischemia/reperfusion (I/R) injury. Bnip3 is involved in the I/R-induced injury. This study investigated whether the effect of PRO on hepatic hypoxia/reoxygenation (H/R) injury was realized through regulating Bnip3. After establishing a hepatic ischemia reperfusion (I/R ) injury model in mice, the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined by an automatic biochemical analyzer. The histopathology and apoptosis of liver tissues were detected by hematoxylin-eosin and TUNEL staining. After the H/R liver cells were cultured and treated with PRO, the viability, apoptosis, reactive oxygen species (ROS) production, and the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), TNF-α, and IL-6 were detected by MTT, flow cytometry, colorimetry, and ELISA. The expressions of Bnip3 and apoptosis-related factors in I/R mouse liver tissues and H/R cells were determined by immunohistochemical assay, immunofluorescence, Western blot, or RT-qPCR. PRO ameliorated the abnormal histopathology, reduced cell apoptosis and the levels of AST, ALT, Bnip3, Cleaved Caspase-3, and Bax, but upregulated the Bcl-2 level in the liver tissues of I/R mice. In H/R liver cells, PRO promoted the cell viability, downregulated the levels of LDH, MDA, TNF-α, IL-6, and reduced ROS production. Moreover, PRO promoted the downregulated expressions of cytosolic Bnip3, total Bni3p, Cleaved Caspase-3, and Bax and upregulated the Bcl-2 level. siBnip3 reversed the effect of H/R on the liver cells, and its overexpression also reversed the effect of PRO on H/R-induced liver cells. PRO protects against hepatic I/R injury via inhibiting Bnip3.
异丙酚(PRO)可预防肝缺血/再灌注(I/R)损伤。Bnip3 参与 I/R 诱导的损伤。本研究探讨了 PRO 对肝缺氧/复氧(H/R)损伤的影响是否是通过调节 Bnip3 实现的。建立小鼠肝缺血再灌注(I/R)损伤模型后,用自动生化分析仪测定血清中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)的水平。用苏木精-伊红和 TUNEL 染色检测肝组织的组织病理学和细胞凋亡。培养 H/R 肝细胞并用 PRO 处理后,通过 MTT、流式细胞术、比色法和 ELISA 检测细胞活力、细胞凋亡、活性氧(ROS)产生以及乳酸脱氢酶(LDH)、丙二醛(MDA)、TNF-α和 IL-6 的水平。免疫组化、免疫荧光、Western blot 或 RT-qPCR 检测 I/R 小鼠肝组织和 H/R 细胞中 Bnip3 和凋亡相关因子的表达。PRO 改善了 I/R 小鼠肝组织的异常组织病理学,减少了细胞凋亡和 AST、ALT、Bnip3、Cleaved Caspase-3 和 Bax 的水平,但上调了 Bcl-2 的水平。在 H/R 肝细胞中,PRO 促进了细胞活力,降低了 LDH、MDA、TNF-α、IL-6 的水平,减少了 ROS 的产生。此外,PRO 促进了细胞质 Bnip3、总 Bni3p、Cleaved Caspase-3 和 Bax 的下调表达,并上调了 Bcl-2 的水平。siBnip3 逆转了 H/R 对肝细胞的作用,其过表达也逆转了 PRO 对 H/R 诱导的肝细胞的作用。PRO 通过抑制 Bnip3 来保护肝脏免受 I/R 损伤。