RESUMO
Liver ischemia reperfusion (IR) injury induces hepatic stellate cell (HSC) activation and liver fibrosis. Propofol (PRO) possesses a positive protective effect on liver ischemia reperfusion injury. We aimed to investigate PRO function and mechanism in IR-induced liver fibrosis. A mice model of liver IR was established. Hematoxylin-eosin (HE) staining was utilized to evaluate liver tissue's pathological changes. Masson staining was applied to evaluate liver fibrosis. The expression level of α-SMA was measured by immunohistochemical (IHC). The expressions of lncRNA HOXA11-AS (HOXA11-AS), PTBP1, HDAC4, α-SMA, COL1A1 and Fibronectin were tested by qRT-PCR or Western blot. The commercial kits detected alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations in serum. Enzyme-linked immunosorbent assay (ELISA) measured TNF-α and IL-6 levels. The binding relationship between HOXA11-AS, PTBP1 and HDAC4 was verified by RNA immunoprecipitation (RIP). Our results showed that PRO alleviated liver fibrosis and the inflammation in IR-induced mice. PRO decreased the expression levels of HOXA11-AS, PTBP1 and HDAC4. Furthermore, HOXA11-AS overexpression abolished the protective effect of PRO against liver fibrosis in mice with IR-disposed. HOXA11-AS interacted with PTBP1 to regulate HDAC4 level and prevented its degradation in JS-1 cells. HDAC4 silencing eliminated the regulatory of HOXA11-AS overexpression on fibrosis and inflammation in IR-induced mice PRO inhibited HOXA11-AS expression to regulate HDAC4, thereby influencing liver fibrosis and inflammation induced by IR. It suggesting that PRO plays a protective role in liver fibrosis induced by ischemia-reperfusion in mice by regulating HOXA11-AS/PTBP1/HDAC4 axis.
Assuntos
Propofol , RNA Longo não Codificante , Traumatismo por Reperfusão , Camundongos , Animais , Propofol/efeitos adversos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/farmacologia , Cirrose Hepática/genética , Cirrose Hepática/induzido quimicamente , Fígado/metabolismo , Isquemia/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de Transcrição/metabolismo , Inflamação/metabolismo , ReperfusãoRESUMO
Lactic acidosis (LA) is characterized by accumulation of lactate in the body, and it may detrimentally affect homeostasis. Perioperative LA is rarely seen, here we presented 2 cases of patients suffered with temporary hyperlactataemia during partial hepatectomy, intended to emphasize that prolonged hypovolemia condition caused by controlled low central venous pressure, and overused hepatic vascular occlusion technique during parenchymal resection of hepatic surgery may seriously impact on the internal environment of patients. And we also discussed how to well manage long-time hepatectomy to prevent LA from occurring and to treat it appropriately.
