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  • Apoptosis type I programmed cell death

    2020-09-11

    Apoptosis, type I programmed cell death, is considered to be involved in the pathogenesis of various liver diseases, such as autoimmune hepatitis [[5], [6], [7], [8], [9], [10]] and hepatocellular carcinoma [11,12]. Apoptosis is activated by a variety of extrinsic or intrinsic pathways factors. Previous research has shown that hepatocyte necrosis and apoptosis occur during hepatic IR injury [4,13]. Furthermore, it has been shown that downregulation of hepatocyte apoptosis exerts a protective effect on hepatic IR injury [1]. Autophagy is also called type II programmed cell death [14]. Autophagy is an evolutionarily-conserved, self-digesting process which promotes cell survival by lysosomal Boc-Phe-Osu receptor [15]; however, overactivated cell autophagy results in cell death. Autophagy is involved in the pathologic processes of a number of diseases, involving hepatic IR injury. Wu et al. [1] found that quercetin significantly attenuates hepatic IR injury by inhibiting autophagy. Levo-tetrahydropalmatine (L-THP) is an active component of the traditional Chinese medicine, Corydalis yanhusuo. L-THP has been used in China for many years as an anxiolytic and sedative in clinics [16]. In recent years, L-THP has shown the potential to treat organ IR injury. Han et al. [17] reported that L-THP could exert protective functions on myocardial IR injury by inhibiting the production of proinflammatory cytokines, including TNF-α and myeloperoxidase (MPO), and alleviating cardiomyocyte apoptosis. Mao et al. [18] showed that L-THP attenuates blood-brain barrier injuries in mice focal cerebral IR injury model; however, the effects of L-THP on hepatic IR injury remain unknown.
    Materials and methods
    Results
    Discussion Hepatic IR injury is a pathophysiologic process that occurs in a variety of common clinical situations, which leads to the high mortality of patients who have undergone liver transplantation or resection of intrahepatic tumors. Furthermore, previous studies have shown that hepatic IR injury also leads to renal and myocardial injury [22,23]. Hence, the mechanism(s) underlying hepatic IR injury needs investigation and effective strategies for hepatic IR injury should be identified. L-THP is the main active component of the traditional Chinese medicine, Corydalis yanhusuo. Recent studies have shown that L-THP exerts protective effects on IR injuries involving the brain and heart [17,18,24] by reducing the release of proinflammatory cytokines and alleviating cell apoptosis. In our study, we confirmed that normal liver function isn\'t affected by the L-THP administration and explored the functions of L-THP pretreatment on hepatic IR injury in mice and its possible mechanism. ALT and AST are liver enzymes whose serum levels increase when hepatocytes die. The serum levels of these two liver enzymes indicate the severity of liver injury [25,26]. It has been found that these two liver enzymes levels of mice in the IR group were significantly higher than that in the sham group. Boc-Phe-Osu receptor L-THP pretreatment downregulated the liver enzymes, and this protective effect was dependent on the dosage of L-THP. These results are further confirmed by the results of pathological changes, indicating that L-THP could alleviate the severity of liver injury induced by hepatic IR. The pathophysiologic processes taking part in hepatic IR injury are complex. In the initial period, the oxidative phosphorylation levels of liver cells decrease due to oxygen deficiency, thus influencing the production of adenosine triphosphate (ATP) [27]. With the depletion of ATP, the swollen hepatocytes produce reactive oxygen species (ROS). Kupffer cells are activated by ROS, then release a variety of proinflammatory cytokines, such as TNF-α and IL-6. Neutrophils and T cells accumulate and are activated by the Kupffer cells, then produce more inflammatory factors, which further aggravates the inflammatory injury in the liver. In our study, we performed ELISA, western blotting, qRT-PCR and immunohistochemistry to detect the inflammatory factors levels in the serum and liver tissues. It has been found that L-THP administration inhibited hepatic IR-induced release of TNF-α and IL-6, and this anti-inflammatory effect is dependent on the dose of L-THP. TNF-α has been previously shown to play a key role in various signal pathways, which could lead to cell apoptosis during hepatic IR injury [1,28].