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

J Tradit Chin Med. 2014 Apr;34(2):178-83. doi: 10.1016/s0254-6272(14)60075-3.

Abstract

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 of 4 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Cytochromes c / metabolism*
  • Drugs, Chinese Herbal / administration & dosage*
  • Humans
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Pancreatitis, Acute Necrotizing / drug therapy*
  • Pancreatitis, Acute Necrotizing / genetics
  • Pancreatitis, Acute Necrotizing / metabolism
  • Pancreatitis, Acute Necrotizing / physiopathology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Drugs, Chinese Herbal
  • Cytochromes c
  • Caspase 3