Improving Small Intestinal Motility in Experimental Acute Necrotising Pancreatitis by Modulating the CPI-17/MLCP Pathway Using Chaiqin Chengqi Decoction

• Published in: Evidence-based complementary and alternative medicine 2020, Vol.2020 (2020), p.1-14
• Main Authors: Jin, Tao, Deng, Lihui, Jiang, Kun, Guo, Jia, Phillips, Anthony R. J., Sutton, Robert, Windsor, John A., Huang, Wei, Xue, Ping, Xia, Qing, Liu, Tingting, Du, Dan, Han, Chengxia, Wen, Yongjian, Shi, Na, Zhang, Xiaoxin, Zhang, Chen-Long, Lin, Ziqi, Yang, Xiaonan
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Calcium (intracellular); Carbachol; Cytokines; Development and progression; Enzyme inhibitors; Enzymes; Fatty acid-binding protein; Fatty acids; Histochemistry; Histopathology; IL-1β; Inflammation; Intestinal motility; Intestine; Jejunum; Kinases; Laboratories; Motility; Muscle contraction; Muscle proteins; Myosin; Myosin-light-chain-phosphatase; Ornithine; Pancreatitis; Penicillin; Phosphatase; Phosphatases; Phosphorylation; Protein binding; Protein kinase C; Protein kinases; Proteins; Signal transduction; Smooth muscle; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vasoactive agents; Vasoactive intestinal peptide; Vasoactive intestinal peptides
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2020/9189457

Protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), a specific inhibitor of myosin light-chain phosphatase (MLCP) regulated by proinflammatory cytokines, is central for calcium sensitisation. We investigated the effects of chaiqin chengqi decoction (CQCQD) on the CPI-17/MLCP pathway in the small intestinal smooth muscle cells (SMCs) and strips (SMS) in an AP model. Necrotising AP was induced in rats by intraperitoneal injections (IPI) of L-ornithine (3.0 g/kg, pH 7.0; hourly × 2) at 1 hour apart; controls received saline. In treatment groups, carbachol (CCh; 60 μg/kg, IPI) or CQCQD (20 g/kg; 2-hourly × 3, intragastric) was administered. The necrotising AP model was associated with systemic inflammation (serum IL-1β and TNF-α) and worsened jejunum histopathology and motility (serum vasoactive intestinal peptide and intestinal fatty acid-binding protein) as the disease progressed. There was decreased intracellular calcium concentration ([Ca2+]i) SMCs. Contractile function of isolated SMCs was reduced and associated with down-regulated expression of key mRNAs and proteins of the CPI-17/MLCP pathway as well as increased IL-1β and TNF-α. CQCQD and CCh significantly reversed these changes and the disease severity. These data suggest that CQCQD can improve intestinal motility by modulating the CPI-17/MLCP pathway in small intestinal smooth muscle during AP.