title: Effect of Chaiqin Chengqi Decoction on cholecystokinin receptor 1-mediated signal transduction of pancreatic acinar cells in acute necrotizing pancreatitis rats.
abstract: OBJECTIVE
  To investigate the effect of Chaiqin Chengqi Decoction (,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(2+)]i.
  
  
  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(2+)]i 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.
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.forename: Zi-Qi
authors.initials: ZQ
authors.lastname: Lin
authors.forename: Xiao-Xiang
authors.initials: XX
authors.lastname: Wang
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.forename: Ping
authors.initials: P
authors.lastname: Xue
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005453:Fluorescence; D005786:Gene Expression Regulation / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010179:Pancreas / Q000473:pathology*; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C000598754:chaiqin chengqi; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium