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

Abstract

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.

• Authors: Ziqi Lin, Chenlong Zhang, Xiaoxin Zhang, Na Shi, Yongjian Wen, Chengxia Han, Dan Du, Tingting Liu, Tao Jin, Lihui Deng, Kun Jiang, Xiaonan Yang, Jia Guo, Anthony Philips, Robert Sutton, John A Windsor, Wei Huang, Ping Xue, Qing Xia
• Journal: Evidence-based complementary and alternative medicine : eCAM (Evid Based Complement Alternat Med) Vol. 2020 Pg. 9189457 ( 2020) ISSN: 1741-427X [Print] United States
• PMID: 32104199 (Publication Type: Journal Article, Retracted Publication)
• Copyright: Copyright © 2020 Ziqi Lin et al.