Therapeutic effect and mechanism of electroacupuncture at Zusanli on plasticity of interstitial cells of Cajal: a study of rat ileum

BMC Complementary and Alternative Medicine

Lin Zhang²  Li-jun Tang²  Yong-hua Wang²  Pei-hong Wang²  Guo-hu Zhang²  Zheng Yang¹  Xiao-yan Zhu³  Chao Wang³  Kun Li³  Mei-fang Peng⁴ 

[1] Department of Preclinical Medicine, Chengdu Medical College, Chengdu 610500, China;Center of General Surgery, Chengdu General Hospital of Chengdu Military Area Command, 270 Rongdu Rd.,Tianhui Town, Jinniu District, Chengdu 610083, China;Basic Laboratory for PLA medical center, Chengdu General Hospital of Chengdu Military Area Command, Chengdu 610083, China;Insititute of Biotechnology and Nuclear Technology, Sichuan Academy of Agricultural Sciences, Chengdu 610061, China

关键词: c-Kit signaling;    Inflammatory mediators;    DOG1;    Plasticity;    Electroacupuncture;   

Others  :  1220107
DOI  :  10.1186/1472-6882-14-186

 received in 2013-09-25, accepted in 2014-05-21,  发布年份 2014

【 摘 要 】

Background

Electroacupuncture (EA) is one of the techniques of acupuncture and is believed to be an effective alternative and complementary treatment in many disorders. The aims of this study were to investigate the effects and mechanisms of EA at acupoint Zusanli (ST36) on the plasticity of interstitial cells of Cajal (ICCs) in partial bowel obstruction.

Methods

A Sprague Dawley rat model of partial bowel obstruction was established and EA was conducted at Zusanli (ST36) and Yinglingquan (SP9) in test and control groups, respectively. Experiments were performed to study the effects and mechanisms of EA at Zusanli on intestinal myoelectric activity, distribution and alteration of ICCs, expression of inflammatory mediators, and c-Kit expression.

Results

1) EA at Zusanli somewhat improved slow wave amplitude and frequency in the partial obstruction rats. 2) EA at Zusanli significantly stimulated the recovery of ICC networks and numbers. 3) the pro-inflammatory mediator TNF-α and NO activity were significantly reduced after EA at Zusanli, However, no significant changes were observed in the anti-inflammatory mediator IL-10 activity. 4) EA at Zusanli re-expressed c-Kit protein. However, EA at the control acupoint, SP9, significantly improved slow wave frequency and amplitude, but had no effect on ICC or inflammatory mediators.

Conclusions

We concluded that EA at Zusanli might have a therapeutic effect on ICC plasticity, and that this effect might be mediated via a decrease in pro-inflammatory mediators and through the c-Kit signaling pathway, but that the relationship between EA at different acupoints and myoelectric activity needs further study.

【 授权许可】

   
2014 Peng et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Ward SM, Sanders KM: Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. I. Functional development and plasticity of interstitial cells of Cajal networks. Am J Physiol Gastrointest Liver Physiol 2001, 281:602-611.
• [2]Torihashi S, Fujimoto T, Trost C, Nakayama S: Calcium oscillation linked to pacemaking of interstitial cells of Cajal. J Biol Chem 2002, 277:19191-19197.
• [3]Bharucha AE, Philips SF: Slow-transit constipation. Curr Treat Opt Gastroenterol 2001, 4:309-315.
• [4]Lyford GL, He CL, Soffer E, Hull TL, Strong SA, Senagore AJ, Burgart LJ, Young-Fadok T, Szurszewski JH, Farrugia G: Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation. Gut 2002, 51:496-501.
• [5]He CL, Burgart L, Wang L, Pemberton J, Young–Fadok T, Szurszewski J, Farrugia G: Decreased interstitial cells of cajal volume in patients with slow-transit constipation. Gastroenterology 2000, 118:14-21.
• [6]Torihashi S, Nishi K, Tokutomi Y, Nishi T, Ward S, Sanders KM: Blockade of kit signaling induces transdifferentiation of interstitial cells of cajal to a smooth muscle phenotype. Gastroenterology 1999, 117:140-148.
• [7]Rich A, Miller SM, Gibbons SJ, Malysz J, Szurszewski JH, Farrugia G: Local presentation of Steel factor increases expression of c-kit immunoreactive interstitial cells of Cajal in culture. Am J Physiol Gastrointest Liver Physiol 2003, 284:313-320.
• [8]Ward SM, Burns AJ, Torihashi S, Sanders KM: Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol 1994, 480(Part 1):91-97.
• [9]Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A: W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 1995, 373:347-349.
• [10]Feldstein AE, Miller SM, El-Youssef M, Rodeberg D, Lindor NM, Burgart LJ, Szurszewski JH, Farrugia G: Chronic intestinal pseudoobstruction associated with altered interstitial cells of Cajal networks. J Pediatr Gastroenterol Nutr 2003, 36:492-497.
• [11]Forster J, Damjanov I, Lin Z, Sarosiek I, Wetzel P, McCallum RW: Absence of the interstitial cells of Cajal in patients with gastroparesis and correlation with clinical findings. J Gastrointest Surg 2005, 9:102-108.
• [12]Pasricha PJ, Pehlivanov ND, Gomez G, Vittal H, Lurken MS, Farrugia G: Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis. BMC Gastroenterol 2008, 8:21.
• [13]Beckett EA, Ro S, Bayguinov Y, Sanders KM, Ward SM: Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract. Dev Dyn 2007, 236:60-72.
• [14]Mei F, Han J, Huang Y, Jiang ZY, Xiong CJ, Zhou DS: Plasticity of interstitial cells of Cajal: a study in the small intestine of adult guinea pigs. Anat Rec 2009, 292:985-993.
• [15]Chang IY, Glasgow NJ, Takayama I, Horiguchi K, Sanders KM, Ward SM: Loss of interstitial cells of Cajal and development of electrical dysfunction in murine small bowel obstruction. J Physiol 2001, 536(2, 12521):555-568.
• [16]Yanagida H, Yanase H, Sanders KM: Intestinal surgical resection disrupts electrical rhythmicity, neural responses, and interstitial cell networks. Gastroenterology 2004, 127:1748-1759.
• [17]Sanders KM, Ordog T, Ward SM: Physiology and pathophysiology of the interstitial cells of Cajal: from bench to bedside: IV. Genetic and animal models of GI motility disorders caused by loss of interstitial cells of Cajal. Am J Physiol Gastrointest Liver Physiol 2002, 282:747-756.
• [18]Turler A, Kalff JC, Moore BA, Hoffman RA, Billiar TR, Simmons RL, Bauer AJ: Leukocyte-derived inducible nitric oxide synthase mediates murine postoperative ileus. Ann Surg 2006, 244:220-229.
• [19]Takeuchi K, Yokota A, Tanaka A, Takahira Y: Factors involved in upregulation of inducible nitric oxide synthase in rat small intestine following administration of nonsteroidal anti-inflammatory drugs. Dig Dis Sci 2006, 51:1250-1259.
• [20]Won KJ, Suzuki T, Hori M, Ozaki H: Motility disorder in experimentally obstructed intestine: relationship between muscularis inflammation and disruption of the ICC network. Neurogastroenterol Motil 2006, 18:53-61.
• [21]Diehl D, Kaplan G, Coulter I, Glik D, Hurwitz EL: Use of acupuncture by American physicians. J Altern Complement Med 1997, 3:119-126.
• [22]Tibosa A, Yamamura Y, Forno ER, Mello LEAM: Effect of acupunctureatST-36 (Zunsanli) and S-6 (Sanyinmiao) on the intestinal myoelectric activity of Wistar rats. Bras J Med Biol Res 2002, 35:731-739.
• [23]Iwa M, Matsushima M, Nakade Y, Pappas TN, Pujiyama M, Takahishi T: Electroacupuncture at ST-36 accelerated colonic motility and transit in freely moving conscious rats. Am J Physiol Gastrointest Liver Physiol 2005, 290:G285-G292.
• [24]Peng M-F, Li K, Zhu X-Y, Wang C, Zhang G-H, Wang Y-H, Tang L-J, Zhang L: Influence of electroacupuncture in Zusanli (ST36) on number and network of interstitial cells Cajal in small intestines in rats with partial intestinal obstruction. J Beijing Univ Tradit Chin Med 2012, 35(8):567-571. 578-579
• [25]Tomita R: Regulation of the peptidergic nerves (substance P and vasoactive intestinal peptide) in the colon of women patients with slow transit constipation:an in vitro study. Hepatogastroenterology 2008, 55:500-507.
• [26]Mawe GM: Interstitial cells of Cahal in the gut: what makes the tick? J Physiol 2009, 587(20):4265.
• [27]Hwang IK, Chung JY, Yoo DY, Yi SS, Youn HY, Seong JK, Yoon YS: Comparing the effects of acupuncture and electroacupuncture at Zusanli and Baihui on cell proliferation and neuroblast differentiation in the rat hippocampus. J Vet Med Sci 2010, 72:279-284.
• [28]Hwang IK, Chung JY, Yoo DY, Yi SS, Youn HY, Seong JK, Yoon YS: Effects of electroacupuncture at Zusanli and Baihui on brain-derived neurotrophic factor and cyclic AMP response element-binding protein in the hippocampal dentate gyrus. J Vet Med Sci 2010, 72:1431-1436.
• [29]Ma SX, Ma J, Moise G, Li XY: Responses of neuronal nitric oxide synthase expression in the brainstem to electroacupuncture Zusanli (ST 36) in rats. Brain Res 2005, 1037:70-77.
• [30]Ward SM, Sanders KM, Hirst GD: Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles. Neurogastroenterol Motil 2004, 16:112-117.
• [31]Mei F, Yu B, Ma H, Zhang HJ, Zhou DS: Interstitial cells of Cajal could regenerate and restore their normal distribution after disrupted by intestinal transection and anastomosis in the adult guinea pigs. Virchows Arch 2006, 449:348-357.
• [32]Ekblad E, Sjuve R, Arner A, Sundler F: Enteric neuronal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum. Gut 1998, 42:836-844.
• [33]Xiao YY, Chen YK, Du L, Pei RQ, Chen FY, Liu GR, Wu RH: The brain mapping of reinforcement acupuncture at ST36 (zusanli) evidenced by fMRI. Conf Proc IEEE Eng Med Biol Soc 2006, 1:1036-1039.
• [34]Lee CH, Jung HS, Lee TY, Yuk SW, Lee KG, Lee BH: Studies of the central neural pathways to the stomach and Zusanli. Am J Chin Med 2001, 29:211-220.
• [35]Gomez-Pinilla PJ, Gibbons SJ, Bardsley MR, Lorincz A, Pozo MJ, Pasricha PJ, Rijn MV, West RB, Sarr MG, Kendrick ML, Cima RR, Dozois EJ, Larson DW, Ordog T, Farrugia G: Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 2009, 296:G1370-G1381.
• [36]West RB, Corless CL, Chen X, Rubin BP, Subramanian S, Montgomery K, Zhu S, Ball CA, Nielsen TO, Patel R, Goldblum JR, Brown PO, Heinrich MC, Rijn M: The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004, 165:107-113.
• [37]Espinosa I, Lee CH, Kim MK, Rouse BT, Subramanian S, Montgomery K, Varma S, Corless CL, Heinrich MC, Smith KS, Wang Z, Rubin B, Nielsen TO, Seitz RS, Ross DT, West RB, Cleary ML, van de Rijn M: A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol 2008, 32:210-218.
• [38]Miwa S, Nakajima T, Murai Y, Takano Y, Sugiyama T: Mutation assay of the novel gene DOG1 in gastrointestinal stromal tumors (GISTs). J Gastroenterol 2008, 43:531-537.
• [39]Liegl B, Hornick JL, Corless CL, Fletcher CDM: Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol 2009, 33:437-446.