Zhang Chen-Long, Lin Zi-Qi, Luo Rui-Jie, Zhang Xiao-Xin, Guo Jia, Wu Wei, Shi Na, Deng Li-Hui, Chen Wei-Wei, Zhang Xiao-Ying, Bharucha Shameena, Huang Wei, Sutton Robert, Windsor John A, Xue Ping, Xia Qing
Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre, West China Hospital, Sichuan University, Chengdu, China.
NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital NHS Trust, University of Liverpool, Liverpool, UK.
Evid Based Complement Alternat Med. 2017;2017:5864945. doi: 10.1155/2017/5864945. Epub 2017 Apr 26.
Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 g/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-1) mRNA and PLC protein (both < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all < 0.05). Neither treatment significantly altered L-arginine-induced PKC-1 and PKC- mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca] (3563.5 and 3046.9 versus 1086.9, both < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca] in colonic SMCs via upregulating PLC, PKC and downregulating AC.
柴芩承气汤(CQCQD)可改善急性胰腺炎(AP)患者的肠道动力,但其作用机制尚待阐明。我们在L-精氨酸诱导的大鼠坏死性AP模型中,研究了CQCQD和促动力剂卡巴胆碱对结肠平滑肌细胞(SMC)的影响。在治疗组中,AP诱导24小时后给予胃内CQCQD(20 g/kg,每2小时1次,共3剂)或腹腔注射卡巴胆碱(60 g/kg)。CQCQD和卡巴胆碱均降低了胰腺和结肠组织病理学的严重程度(均P<0.05)。CQCQD和卡巴胆碱均降低了血清肠脂肪酸结合蛋白、血管活性肠肽和P物质水平,并提高了动力水平。CQCQD上调了SMC磷脂酶C-β1(PLC-1)mRNA和PLC蛋白水平(均P<0.05),与未治疗组相比,两种治疗均上调了蛋白激酶C-α(PKC-α)mRNA和PKC蛋白水平,并下调了腺苷酸环化酶(AC)mRNA和蛋白水平(均P<0.05)。两种治疗均未显著改变L-精氨酸诱导的PKC-1和PKC-ε mRNA降低。两种治疗均显著增加了SMC细胞内钙浓度[Ca]的荧光强度(分别为3563.5和3046.9,而未治疗组为1086.9,均P<0.01)。这些数据表明,CQCQD和卡巴胆碱通过上调PLC、PKC和下调AC来增加结肠SMC中的[Ca],从而改善AP患者的肠道动力。