Abstract
ABSTRACT Acute pancreatitis (AP) is a digestive disease characterized by pancreatic inflammation. Tetramethylpyrazine (TMP) has been effectively used to ameliorate the damage on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP). We aim to study the protective effect of TMP on caerulein-induced AP and to explore the possible mechanism. The mice randomized into control and different experimental groups. AP was induced in mice by 6-hourly intraperitoneal (i.p) injections of caerulein (50 μg/kg at 1 h interval). TMP (i.p, 10 mg/kg, 1 h interval) was administered 3 h before caerulein injection. Administration of TMP attenuated the severity of AP as shown by the histopathology, reduced serum amylase activity and pro-inflammatory cytokines TNF-α and IL-6. Further, TMP enhances the beneficial effect by reducing caerulein-induced NF-κB activation and inducing cell apoptosis in pancreas. Therefore, inhibition of nuclear factor-kappa B(NF-κB) signals by TMP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
Highlights
Acute pancreatitis (AP) is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death [1]
Our findings show that TMP promotes apoptosis and inhibits necrosis, decreases the pancreatic inflammatory response and ameliorates acute pancreatitis in mice through inhibition of NF-κB activation, nuclear p65 translocation and bcl-2 expression
We examined serum IL-6 and TNF-αlevels, and the results showed a significantly enhanced level of IL-6 and TNF-α in the cerulein-induced pancreatitic models, and this was significantly reduced in TMPtreated mice (Figure 2(a)).These data demonstrate that TMP inhibits serum TNF-α and IL-6 levels in cerulein-induced AP in mice
Summary
Acute pancreatitis (AP) is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death [1]. Over the last two decades, our understanding of pathogenesis has advanced, but there is still no specific therapy despite many randomized trials [2]. Specific therapy for AP is lacking and deciphering the molecular mechanisms underlying its pathogenesis will likely aid in therapeutic intervention. The NF-κB is activated early in acinar cells during acute pancreatitis and increases expression of multiple proinflammatory genes, increasing vascular permeability and inducing thrombosis and hemorrhage, leading to tissue necrosis [3,4]. Reducing NF-κB activation and proinflammatory mediators might be a good therapeutic strategy to attenuate AP
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