Chaiqinchengqi decoction regulates necrosis-apoptosis via regulating the release of mitochondrial cytochrome c and caspase-3 in rats with acute necrotizing pancreatitis

OBJECTIVE: To explore the effect and the mechanism of Chaiqinchengqi decoction(CQCQD) on the apoptosis-necrosis switch of pancreatic acinar cells in acute necrotizing pancreatitis(ANP) in rats.METHODS: Sixty Sprague-Dawley rats were randomized into the control group, the ANP group and the CQCQD group. The acute pancreatitis(AP)model was induced by intraperitoneal injections of4 g/kg 8% L-Arginine(PH 7.0) twice with a 1 h interval. Rats in the CQCQD group were intragastrically administered CQCQD(20 mL/kg every 2 h, 3 times,then 20 mL/kg every 6 h, 3 times). Rats were killed at the 6 and 24 h after the induction of AP.The pancreatic tissues were collected for pathology and to isolate pancreatic acinar cells and mitochondria.RESULTS: CQCQD significantly ameliorated the severity of ANP by reducing the pancreatic histopathology score, indicated by lactate dehydrogenase levels at the 6 and 24 h. The CQCQD group promoted the apoptosis of pancreatic acinar cells by raising the apoptosis index compared with the ANP group and the control group. Mitochondrial cytochrome c at the 6 and 24 h in the ANP group were lower than that in the control group or the CQCQD group(0.67±0.13 vs 1.54±0.03 vs 0.81±0.09; 0.71±0.08 vs 1.55±0.09 vs 0.89±0.16, P<0.01). The cytochrome c levels in the cytoplasm at the 6 and 2 h in the CQCQD group were higher than in the control group(1.36±0.15 vs 0.67±0.04, 1.46±0.08 vs 0.59±0.09, P<0.01), or the ANP group(0.96±0.13, P>0.05;0.97±0.09, P<0.05). CQCQD increased caspase-3 activity over the ANP group at the 6 h.CONCLUSION: CQCQD can induce apoptosis and relieve the necrosis of pancreatic acinar cells via promoting the release of mitochondrial cytochrome c and increasing pancreatic caspase-3 activity in ANP rats.