Effect of Chaiqin Chengqi Decoction (柴芩承气汤) on cholecystokinin receptor 1-mediated signal transduction of pancreatic acinar cells in acute necrotizing pancreatitis rats.

Objective: To investigate the effect of Chaiqin Chengqi Decoction (柴芩承气汤,CQCQD) on cholecystokinin receptor 1 (CCKR1)-mediated signal transduction of pancreatic acinar cell in rats with acute necrotic pancreatitis (ANP). Methods: Twenty-seven Sprague-Dawley rats were randomized into three groups: the control group, the ANP group, and the CQCQD group (9 in each group). ANP rats were induced by two intraperitoneal injections of 8% L-arginine (pH=7.0, 4.4 g/kg) over a 2-h period. Rats were treated with 1.5 mL/100 g body weight of CQCQD (CQCQD group) or physiological saline (control and ANP groups) at 2 h interval. And 6 h after induction, pancreatic tissues were collected for histopathological examination. Pancreatic acinar cells were isolated for determination of CCKR1 mRNA and protein expression, phospholipase C (PLC) and inositol-1,4,5-triphosphate (IP3), and determination of fluorescence intensity (FI) as a measure of intracellular calcium ion concentration [Ca]. Results: The pancreatic histopathological score (6.2±1.1) and the levels of PLC (1,187.2±228.2 μg/mL) and IP3 (872.2±88.4 μg/mL) of acinar cells in the ANP group were higher than those in the control (2.8±0.4, 682.5±121.8 μg/mL, 518.4±115.8 μg/mL) and the CQCQD (3.8±0.8, 905.3±78.5 μg/mL, 611.0±42.5 μg/mL) groups ( P<0.05). [Ca] FI for the ANP group (34.8±27.0) was higher than that in the control (5.1±2.2) and CQCQD (12.6±2.5) groups ( P<0.05). The expression of pancreatic acinar cell CCKR1 mRNA in the ANP group was up-regulated (expression ratio=1.761; P=0.024) compared with the control group. The expression of pancreatic acinar cell CCKR1 mRNA in the CQCQD group was down-regulated (expression ratio=0.311; P=0.035) compared with the ANP group. The ratio of gray values of the CCKR1 and β-actin in the ANP group (1.43±0.17) was higher than those in the control (0.70±0.15) and CQCQD (0.79±0.11) groups ( P<0.05). Conclusions: Pancreatic acinar cell calcium overload of ANP induced by L-arginine was related to the up-regulated expressions of pancreatic acinar cell CCKR1 mRNA and protein. CQCQD can down-regulate expressions of pancreatic acinar cell CCKR1 mRNA and protein to reduce the PLC and IP3 of pancreatic acinar cells, relieving the calcium overload and reducing the pathological changes in rats with ANP. [ABSTRACT FROM AUTHOR]