C-Kit expression in the gallbladder of guinea pig with chronic calculous cholecystitis and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal

Document Type: Original Article


1 Department of General Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116000, China

2 Department of Physical Examination, First Affiliated Hospital, Dalian Medical University, Dalian 116000, China


Objective(s): To study the c-Kit expression in the gallbladder of cholesterol lithogenic guinea pig model and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal (ICCs).
Materials and Methods:A total of 45 guinea pigs were randomly assigned into three groups: the control group (guinea pigs fed a standard diet, normal group); the model group (guinea pigs fed a cholesterol gallstone-inducing diet); and the Chinese medicine group (guinea pigs fed the cholesterol gallstone-inducing diet and treated with A. capillaris through intragastric administration, therapy group). Each group had 15 guinea pigs. The gallbladders of the guinea pigs were harvested after 8 weeks. C-Kit expression was detected using an immunohistochemistry staining, real-time PCR, and Western blot analyses. The effect of A. capillaris on ICCs was evaluated by muscle strip contraction experiments.
Results: C-Kit expression significantly decreased in the gallbladder of model group, but increased in the Chinese medicine group. The Contractility of guinea pig gallbladder muscle strip significantly improved in the Chinese medicine group.
Conclusion: Our results indicated that A. capillaris improves gallbladder impairment by up-regulating c-Kit expression, and it also can improve the contractile response of in vitro guinea pig gallbladder muscle strips.


1. Zhang JH, Yang KZ, Han BL. The kinetic mechanism of gallstone formation. Chin J Gen Surg 2001; 16:424-426.

2. Maurer KJ, Carey MC, Fox JG. Roles of infection, inflammation, and the immune system in cholesterol gallstone formation. Gastroenterology 2009; 136:425-440.

3. Sanders KM. A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology 1996; 111:492-515.

4. Huang Y, Mei F, Yu B, Zhang HJ, Han J, Jiang ZY, et al. Distribution of the interstitial Cajal-like cells in the gallbladder and extrahepatic biliary duct of the guinea pig. Acta Histochem 2009; 111:157-165.

5. Hinescu ME, Ardeleanu C, Gherghiceanu M, Popescu LM. Interstitial Cajal-like cells in human gallbladder. J Mol Histol 2007; 38:275-284.

6. Balemba OB, Salter MJ, Heppner TJ, Bonev AD, Nelson MT, Mave GW. Spontaneous electrical rhythemicity and the role of the sacroplasmic reticulum in the excitability of guinea pi-g gallbladder smoth muscle cells. Am J Gastrointest Liver Physiol 2006; 290:G665-G674.

7. Hu WM, Luo HS, Ding XW, Wang L. Experssion of c-Kit messenger ribonucleic acid and c-Kit protein in the gallbladders in guinea pigs of high cholesterol diet. Dig Dis Sci 2009; 54:1651-1655.

8. Konturek JW, Scott GW, Kingma JY. Electral activity of canine gallbladder. Physiolpharmacol 1991; 42:85-91.

9. Lavoie B, Balemba OB, Nelson MT, Ward SM, Mawe GM. Morphological and physiological evidence for interstitial cell of Cajal-like cells in the guinea pig gallbladder. J Physiol 2007; 579:487-501.

10. Xu D, Yu BP, Luo HS, Chen LD. Control of gallbladder contractions by cholecystokinin through cholecystokinin-A receptors on gallbladder interstitial cells of cajal. World J Gastroenterol 2008; 14: 2882-2887.

11. Torihashi S, Ward SM, Nishikawa S, Nishi K, Kobayashi S, Sanders KM. c-Kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res 1995; 280:97-111.

12.Torihashi S, Yokoi K, Nagaya H, Aoki K, Fujimoto T. New monoclonal anti-body (AIC) identifies interstitial cells of Cajal in the musculature of the mouse gastrointestinal tract. Auton Neurosci 2004; 113(1-2):16-23.

13. Piaseczna-Piotrowska AM, Dzieniecka M, Kulig A, Danilewicz M, Chilarski A. Different distribution of c-kit positive interstitial cells of Cajal-like in children's urinary bladders. Folia Histochem Cytobiol 2011; 49:431-435.

14. Burns AJ, Herbert TM, Ward SM, Sanders KM. Interstitial cells of Cajal in the guinea-pig gastrointestinal tract as revealed by c-Kit immunohistochemistry. Cell Tissue Res 1997; 290:11-20.

15. Iino S, Horiguchi S, Horiguchi K. Interstitial cells of Cajal in the gastrointestinal musculature of W(jic) c-kit mutant mice. J Smooth Muscle Res 2011; 47:111-121.

16. Mu YP, Liu P, Wang L. Evolution and modern research of Yinchenhao decoction. Chin J Exp Tradition Medical Formulae 2006; 12:67-71.

17. Wu YX, Zhang SY. The treatment experience of gallbladder polyps by modified Yinchenhao decoction. Clin J Tradition Chin Med 2011; 23:642.

18. Li YX, Chen SL. The observation through B-scan of 25 kinds of traditional Chinese medicine on gallbladder motility. China J Chinese Materia Medica1995; 20:754-756.

19. Everson GT. Gallbladder function in gallstone disease. Gastroenterol Clin North Am 1991; 20:85-110.

20. Jazrawi RP, Pazzi P, Petroni ML, Prandini N, Paul C, Adam JA, et al.  Postgrandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis. Gastroenterology 1995; 109:582-591.

21. Xu QW, Shaffer EA. Cisapride improves gallbladder contractility and bile lipid composition in an animal model of gallstone disease. Gastroenterology 1993; 105:1184.

22. Zhang DL, Qi QH, Li Y, Zhou L, Xu SY, Fan XF, et al. Kinetics mechanism study of tongli gongxia formula treating guinea pigs with calculous cholecystitis. Chin Arch Tradition Chin Med 2012; 30:2210-2212.

23. Komuro T. Structure and organization of interstitial cells of Cajal in the gastrointes tinal tract. J Physiol 2006; 576:653-658.

24. Goodenough DA, Goliger JA, Paul DL. Connexins, nexons, and intercellular Communication. Annu Rev Biochem 1996; 65:475-502.

25. Kern F. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones. J Clin Invest 1994; 93:1186-1194.

26. Zhou WJ, Yang YM, Fang YM, Wei ZM. Establishment of guinea pig molel of cholesterol calculus in gallbladder. Chin J Lab Anim Sci 1999; 9:198-200.

27. Fang BJ, Zhou S, Pei XJ, Huang JY, Chen BJ, Geng Y, et al. Effects of Yanggan Lidan Granule on insulin resistance in guinea pigs with induced cholesterol gallstones. Am J Epidemiol 2009; 7:1159-1163.

28. Hua Y, Feng J, Li FZ. Progress in study on cholagogue active components of yinchenhao decoction. Chin Arch Tradition Chin Med 2011; 29:1520-1521.