Changes of Amount of Interstitial Cells of Cajal and Expression of SCF/c-Kit in The Process of Cathartic Colon Induced by Emodin in Mice_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HUANGWei ^1,2 , TANGLi-jun ² , ZHANGGuo-hu ² , WANGPei-hong ² , LIKun ³ , LIWei ³ , GURui ³ ,  ZHANGLin ^1,2

1. Department of Gastrointestinal Surgery, Center for General Surgery, General Hospital of Chendu Military Area of Chinese PLA, Chengdu 610083, Sichuan Province, China;
2. Southwest Medical University Clinical Medical College, Luzhou 646000, Sichuan Province, China;
3. Basic Laboratory of Medical Center, General Hospital of Chendu Military Area of Chinese PLA, Chengdu 610083, Sichuan Province, China;

Corresponding?author：

ZHANGLin, Email: flysky8026@aliyun.com

Keywords：

Emodin; Cathartic colon; Interstitial cell of Cajal; Stem cell factor; c-Kit protein

DOI：

10.7507/1007-9424.20160109

Video：

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Objective To investigate the changes of amount of interstitial cells of Cajal (ICC) and expression of stem cell factor (SCF)/c-Kit in the process of cathartic colon induced by emodin in mice. Methods A modified cathartic colon mouse model was established. Seventy-two healthy male Kunming (KM) mice were randomly divided into the blank control group and sustained drug delivery group.Morphological changes of colon in mice were observed; frozen section immunofluorescence was used to observed changes of amount of ICC; serum concentrations of SCF were examined by ELISA; Western blot was employed for observation of expression of SCF/c-Kit in colon. Results After the mice model were completed, the weight of mouse, length and diameter of entire colon were all reduced compared with the blank control group. The amount of ICC appeared to decline in the beginning of the first 6 weeks with emodin used, and significant decreased in 10-12 weeks. The serum concentrations of SCF first began to decline in 4 weeks with emodin used, and significantly decreased in 6 weeks, and continued at a low level after 8 weeks. The expression of c-Kit in colon began to decline in 4 weeks with emodin used and significantly reduced after 8 weeks. Conciusions The amount of ICC appear to slowly decline in the beginning of the first 12 weeks with emodin used, and significant decrease after 12 weeks.The serum concentrations of SCF and expression of c-Kit in colon have the dynamic changes in the meanwhile, and the changes of SCF are earlier than that of c-Kit. The trend of amount ofICC may have a certain relationship with changes of SCF and c-Kit.

Citation： HUANGWei, TANGLi-jun, ZHANGGuo-hu, WANGPei-hong, LIKun, LIWei, GURui, ZHANGLin. Changes of Amount of Interstitial Cells of Cajal and Expression of SCF/c-Kit in The Process of Cathartic Colon Induced by Emodin in Mice. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(4): 406-410. doi: 10.7507/1007-9424.20160109 Copy

1.	Bharucha AE, Pemberton JH, Locke GR 3rd. American gastroen terological association technical review on constipation. Gastroen terology, 2013, 144(1):218-238.
2.	Bove A, Bellini M, Battaglia E, et al. Consensus statement AIGO/SICCR diagnosis and treatment of chronic constipation and obstru cted defecation(partⅡ:treatment). World J Gastroenterol, 2012, 18 (36):4994-5013.
3.	Lee JI, Park H, Kamm MA, et al. Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit consti pation and acquired megacolon. J Gastroenterol Hepatol, 2005, 20 (8):1292-1298.
4.	Zhu MH, Sung TS, O'driscoll K, et al. Intracellular Ca2+ release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal. Ajp Cell Physiology, 2015, 308(8):C608-C620.
5.	Huizinga JD, Chen JH. Interstitial cells of Cajal:update on basic and clinical science. Curr Gastroenterol Rep, 2014, 16(1):363.
6.	Chen ZH, Zhang YC, Jiang WF, et al. Characterization of interstitial Cajal progenitors cells and their changes in Hirschsprung's disease. PLoS One, 2014, 9(1):e86100.
7.	Tan YY, Ji ZL, Zhao G, et al. Decreased SCF/c-kit signaling pathway contributes to loss of interstitial cells of Cajal in gallstone disease. Int J Clin Exp Med, 2014, 7(11):4099-4106.
8.	蔣楠, 余躍, 陳鳳琴, 等.半夏瀉心湯對糖尿病大鼠胃竇Cajal間質細胞及干細胞因子的影響.中國中西醫結合雜志, 2013, 33 (12):1672-1676.
9.	劉興, 王文革, 次苗苗.大黃酸與大黃建立大鼠"瀉劑結腸"模型的比較.世界華人消化雜志, 2014, 22(9):1262-1265.
10.	吳勁松, 劉寶華, 童衛東, 等.瀉劑結腸大鼠模型阿片受體表、達變化.第三軍醫大學學報, 2013, 35(21):2278-2281.
11.	Shin DH, Lee MJ, Jiao HY, et al. Regulatory roles of endogenous mitogen-activated protein kinases and tyrosine kinases in the pace maker activity of colonic interstitial cells of Cajal. Pharmacology, 2015, 96(1-2):16-24.
12.	Mei F, Han J, Huang Y, et al. Plasticity of interstitial cells of cajal:a study in the small intestine of adult Guinea pigs. Anat Rec (Hoboken), 2009, 292(7):985-993.
13.	張卉, 苗芙蕊, 羅鈺瑩, 等.壯醫藥線點灸療法對糖尿病性胃輕癱大鼠胃竇Cajal間質細胞的影響.針刺研究, 2015, 40(2):104-107, 118.
14.	Lee S, Gim H, Shim JH, et al. The traditional herbal medicine, Ge-Gen-Tang, inhibits pacemaker potentials by nitric oxide/cGMP dependent ATP-sensitive K⁺ channels in cultured interstitial cells of Cajal from mouse small intestine. J Ethnopharmacol. 2015, 170:201-209.
15.	Angeli TR, Cheng LK, Du P, et al. Loss of interstitial cells of Cajal and patterns of gastric dysrhythmia in patients with chronic unexp lained nausea and vomiting. Gastroenterology, 2015, 149(1):56-66.
16.	Lin L, Xu LW, Zhang W, et al. Roles of stem cell factor on the deple tion of interstitial cells of Cajal in the colon of diabetic mice. Am J Physiol Gastrointest Liver Physiol, 2010, 298(2):G241-G247.
17.	Horváth VJ, Vittal H, L?rincz A, et al. Reduced stem cell factor links smooth myopathy and loss of interstitial cells of Cajal in murine diabetic gastroparesis. Gastroenterology, 2006, 130(3):759-770.
18.	Bashamboo A, Taylor AH, Samuel K, , et al. The survival of differen tiating embryonic stem cells is dependent on the SCF-KIT pathway. J Cell Sci, 2006, 119(Pt 15):3039-3046.
19.	Lin XL, Tang XD, Cai ZX, et al. NPs/NPRs signaling pathways may be involved in depression-induced loss of gastric ICC by decreasing the production of mSCF. Plos One, 2016, 11(2):e0149031.
20.	Li XS, Xue H, Kang Q, et al. Alterations of the interstitial cells of Cajal and the microstructure of the gastrointestinal tract in KIT distal kinase mutant mice. Cell Tissue Res, 2014, 355(1):49-58.
21.	Tong W, Jia HL, Zhang L, et al. Exogenous stem cell factor improves interstitial cells of Cajal restoration after blockade of c-kit signaling pathway. Scand J Gastroenterol, 2010, 45(7-8):844-851.
22.	Iqbal F, Samuel M, Tan EJ, et al. Letter:orlistat as a potential treat ment for chronic idiopathic constipation. Aliment Pharmacol Ther, 2016, 43(7):848-849.
23.	Vazquez Roque M, Bouras EP. Epidemiology and management of chronic constipation in elderly patients. Clin Interv Aging, 2015, 10:919-930.
24.	駱元斌, 顧立萍, 黃小玲, 等.蒽醌類中藥致結腸黑變病發病機制探討.中國中西醫結合消化雜志, 2014, 22(2):78-79.
25.	Hong KS, Jung KW, Lee TH, et al. Current issues on the treatment of chronic constipation. Korean J Gastroenterol, 2014, 64(3):148-153.
26.	De Giorgio R, Cestari R, Corinaldesi R, et al. Use of macrogol 4000 in chronic constipation. Eur Rev Med Pharmacol Sci, 2011, 15(8):960-966.

1. Bharucha AE, Pemberton JH, Locke GR 3rd. American gastroen terological association technical review on constipation. Gastroen terology, 2013, 144(1):218-238.
2. Bove A, Bellini M, Battaglia E, et al. Consensus statement AIGO/SICCR diagnosis and treatment of chronic constipation and obstru cted defecation(partⅡ:treatment). World J Gastroenterol, 2012, 18 (36):4994-5013.
3. Lee JI, Park H, Kamm MA, et al. Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit consti pation and acquired megacolon. J Gastroenterol Hepatol, 2005, 20 (8):1292-1298.
4. Zhu MH, Sung TS, O'driscoll K, et al. Intracellular Ca2+ release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal. Ajp Cell Physiology, 2015, 308(8):C608-C620.
5. Huizinga JD, Chen JH. Interstitial cells of Cajal:update on basic and clinical science. Curr Gastroenterol Rep, 2014, 16(1):363.
6. Chen ZH, Zhang YC, Jiang WF, et al. Characterization of interstitial Cajal progenitors cells and their changes in Hirschsprung's disease. PLoS One, 2014, 9(1):e86100.
7. Tan YY, Ji ZL, Zhao G, et al. Decreased SCF/c-kit signaling pathway contributes to loss of interstitial cells of Cajal in gallstone disease. Int J Clin Exp Med, 2014, 7(11):4099-4106.
8. 蔣楠, 余躍, 陳鳳琴, 等.半夏瀉心湯對糖尿病大鼠胃竇Cajal間質細胞及干細胞因子的影響.中國中西醫結合雜志, 2013, 33 (12):1672-1676.
9. 劉興, 王文革, 次苗苗.大黃酸與大黃建立大鼠"瀉劑結腸"模型的比較.世界華人消化雜志, 2014, 22(9):1262-1265.
10. 吳勁松, 劉寶華, 童衛東, 等.瀉劑結腸大鼠模型阿片受體表、達變化.第三軍醫大學學報, 2013, 35(21):2278-2281.
11. Shin DH, Lee MJ, Jiao HY, et al. Regulatory roles of endogenous mitogen-activated protein kinases and tyrosine kinases in the pace maker activity of colonic interstitial cells of Cajal. Pharmacology, 2015, 96(1-2):16-24.
12. Mei F, Han J, Huang Y, et al. Plasticity of interstitial cells of cajal:a study in the small intestine of adult Guinea pigs. Anat Rec (Hoboken), 2009, 292(7):985-993.
13. 張卉, 苗芙蕊, 羅鈺瑩, 等.壯醫藥線點灸療法對糖尿病性胃輕癱大鼠胃竇Cajal間質細胞的影響.針刺研究, 2015, 40(2):104-107, 118.
14. Lee S, Gim H, Shim JH, et al. The traditional herbal medicine, Ge-Gen-Tang, inhibits pacemaker potentials by nitric oxide/cGMP dependent ATP-sensitive K⁺ channels in cultured interstitial cells of Cajal from mouse small intestine. J Ethnopharmacol. 2015, 170:201-209.
15. Angeli TR, Cheng LK, Du P, et al. Loss of interstitial cells of Cajal and patterns of gastric dysrhythmia in patients with chronic unexp lained nausea and vomiting. Gastroenterology, 2015, 149(1):56-66.
16. Lin L, Xu LW, Zhang W, et al. Roles of stem cell factor on the deple tion of interstitial cells of Cajal in the colon of diabetic mice. Am J Physiol Gastrointest Liver Physiol, 2010, 298(2):G241-G247.
17. Horváth VJ, Vittal H, L?rincz A, et al. Reduced stem cell factor links smooth myopathy and loss of interstitial cells of Cajal in murine diabetic gastroparesis. Gastroenterology, 2006, 130(3):759-770.
18. Bashamboo A, Taylor AH, Samuel K, , et al. The survival of differen tiating embryonic stem cells is dependent on the SCF-KIT pathway. J Cell Sci, 2006, 119(Pt 15):3039-3046.
19. Lin XL, Tang XD, Cai ZX, et al. NPs/NPRs signaling pathways may be involved in depression-induced loss of gastric ICC by decreasing the production of mSCF. Plos One, 2016, 11(2):e0149031.
20. Li XS, Xue H, Kang Q, et al. Alterations of the interstitial cells of Cajal and the microstructure of the gastrointestinal tract in KIT distal kinase mutant mice. Cell Tissue Res, 2014, 355(1):49-58.
21. Tong W, Jia HL, Zhang L, et al. Exogenous stem cell factor improves interstitial cells of Cajal restoration after blockade of c-kit signaling pathway. Scand J Gastroenterol, 2010, 45(7-8):844-851.
22. Iqbal F, Samuel M, Tan EJ, et al. Letter:orlistat as a potential treat ment for chronic idiopathic constipation. Aliment Pharmacol Ther, 2016, 43(7):848-849.
23. Vazquez Roque M, Bouras EP. Epidemiology and management of chronic constipation in elderly patients. Clin Interv Aging, 2015, 10:919-930.
24. 駱元斌, 顧立萍, 黃小玲, 等.蒽醌類中藥致結腸黑變病發病機制探討.中國中西醫結合消化雜志, 2014, 22(2):78-79.
25. Hong KS, Jung KW, Lee TH, et al. Current issues on the treatment of chronic constipation. Korean J Gastroenterol, 2014, 64(3):148-153.
26. De Giorgio R, Cestari R, Corinaldesi R, et al. Use of macrogol 4000 in chronic constipation. Eur Rev Med Pharmacol Sci, 2011, 15(8):960-966.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Changes of Amount of Interstitial Cells of Cajal and Expression of SCF/c-Kit in The Process of Cathartic Colon Induced by Emodin in Mice

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