Tetramethylpyrazine can ameliorate hepatocellular mitochondrial dysfunction by decreasing the inflammatory response and increasing AQP8 protein expression in septic rats:

摘要

Sepsis, which could lead to mitochondrial dysfunction and cellular energy loss, always induces acute liver injury and has a high mortality rate. Tetramethylpyrazine (TMP) is an active extract from the Chinese herb Ligusticum chuanxiong and exhibits anti-sepsis activity. In this study, a rat sepsis model was first established via cecal ligation and puncture (CLP). Then, 48 Sprague Dawley male rats were randomly divided into four groups (12 rats in each group): control group (C), sepsis group (S), TMP treatment group (T), and TMP prevention group (P). Serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), mitochondrial aspartate aminotransferase (mAST), and adenosine triphosphate (ATP) levels and mitochondrial membrane potential (MMP) were measured and used as indicators of hepatic dysfunction severity and mitochondrial function. In addition, the activities of Na+-K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, and Ca2+-Mg2+-ATPase in the mitochondrial membrane, the expression level of AQP8 and some inflammatory factors, and the level of oxidative stress were measured to explore potential mechanisms. We found that AQP8 accepts signals from inflammatory factors upon stimulation and during various infections, and low AQP8 expression levels could result in further downstream mitochondrial dysfunction. In conclusion, our data demonstrated that TMP could ameliorate hepatocellular mitochondrial dysfunction by decreasing the inflammatory response and increasing AQP8 protein expression.