Integrated traditional Chinese medicine improves acute pancreatitis via the downregulation of PRSS1 and SPINK1

Gao,Qiang; Liang,Nusheng

doi:10.3892/etm.2015.2191

Integrated traditional Chinese medicine improves acute pancreatitis via the downregulation of PRSS1 and SPINK1

Authors:
- Qiang Gao
- Nusheng Liang
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Affiliations: Physician Department, Health Service Center, Nyalam, Tibet 858300, P.R. China, Department of Gastroenterology, First Hospital of Tianjin, Tianjin 300193, P.R. China
Published online on: January 20, 2015 https://doi.org/10.3892/etm.2015.2191
Pages: 947-954

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Abstract

Integrated traditional Chinese medicine (ITCM) is known to improve health in patients with acute pancreatitis (AP); however, the molecular mechanisms underlying this effect are unknown. AP is associated with the expression of PRSS1 and SPINK1. Thus, the present study aimed to investigate whether ITCM was able to ameliorate AP by regulating the expression levels of protein, serine 1 (PRSS1) and serine peptidase inhibitor, Kazal type 1 (SPINK1). A total of 100 AP patients were divided at random into two groups. The treatment group were treated externally with a herbal ITCM preparation, while the control group received a routine placebo treatment. The mRNA and protein expression levels of PRSS1 and Spink1 were subsequently compared between the two groups. The results revealed that the health of the patients who had received ITCM improved significantly when compared with the control group patients (P<0.05). In addition, the expression levels of PRSS1 and SPINK1 were found to be lower in the treatment group when compared with the control group (P<0.05). Therefore, ITCM exhibited a significant therapeutic effect on AP and produced no side effects since the treatment was applied externally. ITCM may ameliorate AP by downregulating the expression of PRSS1 and SPINK1; thus, should be considered as a potential therapy for the development of drugs against AP.

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1	Matta A, Tandra PK, Cichowski E and Reddymasu SC: Acute necrotising pancreatitis: a late and fatal complication of pancreaticoduodenal arterial embolisation. BMJ Case Rep. bcr20142041972014. View Article : Google Scholar : PubMed/NCBI
2	Rana SS, Sharma V, Sharma R and Bhasin DK: An unusual complication of acute necrotising pancreatitis detected by endoscopic ultrasound. JOP. 15:276–277. 2014.PubMed/NCBI
3	Ambiru S, Furuyama N, Aono M, et al: Hyperbaric oxygen therapy for the treatment of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery: experience with 626 patients. Hepatogastroenterology. 54:1925–1929. 2007.
4	Sheikh I, Fontenot E, Waghray N, et al: The role of nonsteroidal anti-inflammatory drugs in the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis. JOP. 15:219–224. 2014.PubMed/NCBI
5	Sit M, Aktas G, Yilmaz EE, et al: Effects of the inflammatory response on serum omentin levels in early acute and chronic pancreatitis. Clin Ter. 165:e148–e152. 2014.PubMed/NCBI
6	Shalimov SA, Popov ON, Dubitskiĭ AE and Lifshits IuZ: Direct thermometry of the pancreas in the postoperative period. Vestn Khir Im I I Grek. 132:36–39. 1984.(In Russian). PubMed/NCBI
7	Mascolo N, Izzo AA, Ligresti A, et al: The endocannabinoid system and the molecular basis of paralytic ileus in mice. FASEB J. 16:1973–1975. 2002.PubMed/NCBI
8	Elder AS, Saccone GT, Bersten AD and Dixon DL: Evaluation of lung injury and respiratory mechanics in a rat model of acute pancreatitis complicated with endotoxin. Pancreatology. 12:240–247. 2012. View Article : Google Scholar : PubMed/NCBI
9	Fujita T: Endotoxin as a trigger of alcoholic pancreatitis. Gastroenterology. 134:640–641. 2008. View Article : Google Scholar : PubMed/NCBI
10	Verma R, Dhamija R, Ross SC, Batts DH and Loehrke ME: Symbiotic bacteria induced necrotizing pancreatitis. JOP. 11:474–476. 2010.PubMed/NCBI
11	Zhang X, Tian H, Wu C, et al: Effect of baicalin on inflammatory mediator levels and microcirculation disturbance in rats with severe acute pancreatitis. Pancreas. 38:732–738. 2009. View Article : Google Scholar : PubMed/NCBI
12	Cuthbertson CM and Christophi C: Disturbances of the microcirculation in acute pancreatitis. Br J Surg. 93:518–530. 2006. View Article : Google Scholar : PubMed/NCBI
13	Yang XN, Guo J, Lin ZQ, et al: The study on causes of death in fulminant pancreatitis at early stage and late stage. Sichuan Da Xue Xue Bao Yi Xue Ban. 42:686–690. 2011.(In Chinese). PubMed/NCBI
14	Yuan Z, Meyerholz DK, Twait EC, et al: Systemic inflammation with multiorgan dysfunction is the cause of death in murine ligation-induced acute pancreatitis. J Gastrointest Surg. 15:1670–1678. 2011. View Article : Google Scholar : PubMed/NCBI
15	Tsuji Y, Takahashi N, Fletcher JG, et al: Subtraction color map of contrast-enhanced and unenhanced CT for the prediction of pancreatic necrosis in early stage of acute pancreatitis. AJR Am J Roentgenol. 202:W349–W356. 2014. View Article : Google Scholar : PubMed/NCBI
16	Garip G, Sarandöl E and Kaya E: Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis. World J Gastroenterol. 19:8065–8070. 2013. View Article : Google Scholar : PubMed/NCBI
17	Popa D: Treatment in severe acute pancreatitis - still a reason of debate. J Med Life. 6:486–490. 2013.
18	Ge HY and Chen B: Clinical observation of acute pancreatitis treated with acupoint application combined with medicine. Zhongguo Zhen Jiu. 32:602–604. 2012.(In Chinese). PubMed/NCBI
19	Bossi A, Romeo G and Pezzoli A: Side-effects, structure, and H2-receptor antagonists. Lancet. 339:13661992. View Article : Google Scholar : PubMed/NCBI
20	Xia Q and Deng LH: Hot issues on the treatment of severe acute pancreatitis by integrated traditional Chinese and Western medicine. Sichuan Da Xue Xue Bao Yi Xue Ban. 44:962–965. 2013.(In Chinese).
21	Wan MH, Yao J, Li J, et al: The effectiveness of purgation and electroacupuncture in extrahepatic bile duct stone complicated with acute biliary pancreatitis: management of biliary stone pancreatitis through traditional Chinese medicine. Pancreas. 40:483–484. 2011. View Article : Google Scholar : PubMed/NCBI
22	Tang Y, Liao Y, Kawaguchi-Sakita N, et al: Sinisan, a traditional Chinese medicine, attenuates experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid in rats. J Hepatobiliary Pancreat Sci. 18:551–558. 2011. View Article : Google Scholar : PubMed/NCBI
23	Solomon S, Whitcomb DC and LaRusch J: PRSS1-related hereditary pancreatitis. GeneReviews^®. Pagon RA, Adam MP, Ardinger HH, et al: University of Washington; Seattle, WA: 2012
24	Sánchez-Ramírez CA, Flores-Martínez SE, García-Zapién AG, et al: Screening of R122H and N29I mutations in the PRSS1 gene and N34S mutation in the SPINK1 gene in Mexican pediatric patients with acute and recurrent pancreatitis. Pancreas. 41:707–711. 2012.PubMed/NCBI
25	Tukiainen E, Kylänpää ML, Kemppainen E, et al: Pancreatic secretory trypsin inhibitor (SPINK1) gene mutations in patients with acute pancreatitis. Pancreas. 30:239–242. 2005. View Article : Google Scholar : PubMed/NCBI
26	Lee YJ, Kim KM, Choi JH, et al: High incidence of PRSS1 and SPINK1 mutations in Korean children with acute recurrent and chronic pancreatitis. J Pediatr Gastroenterol Nutr. 52:478–481. 2011. View Article : Google Scholar : PubMed/NCBI
27	Sobczyńska-Tomaszewska A, Bak D, Oralewska B, et al: Analysis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or chronic pancreatitis. J Pediatr Gastroenterol Nutr. 43:299–306. 2006. View Article : Google Scholar
28	Kiriyama S, Gabata T, Takada T, et al: New diagnostic criteria of acute pancreatitis. J Hepatobiliary Pancreat Sci. 17:24–36. 2010. View Article : Google Scholar
29	Gubergrits N, Golubova O, Lukashevich G and Fomenko P: Elevated serum amylase in patients with chronic pancreatitis: acute attack or macroamylasemia? Pancreatology. 14:114–116. 2014. View Article : Google Scholar : PubMed/NCBI
30	Wojtuń S and Gil J: Utility of amylase serum and urine activity in acute biliary pancreatitis treated with biliary sphincterotomy. Pol Merkur Lekarski. 22:381–384. 2007.(In Polish).
31	Banks PA, Bollen TL, Dervenis C, et al; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis - 2012: revision of the Atlanta classification and definitions by international consensus. Gut. 62:102–111. 2013. View Article : Google Scholar
32	Li YC, Dong L, Jia A, Chang XM and Xue H: Preparation of solid lipid nanoparticles loaded with traditional Chinese medicine by high-pressure homogenization. Nan Fang Yi Ke Da Xue Xue Bao. 26:541–544. 2006.(In Chinese). PubMed/NCBI
33	Zhuang WJ and Qian C: Treatment of infected deciduous root canal with Samyan (traditional Chinese medicine) paste: Clinical analysis. Shanghai Kou Qiang Yi Xue. 6:1851997.(In Chinese).
34	Xue QM, Li N, Xue P, Wang CW and Wen Q: Therapeutic effects of electroacupuncture at ST36 acupoint on sodium-taurocholate-induced severe acute pancreatitis. Chin J Integr Med. 20:695–700. 2014. View Article : Google Scholar
35	Saito Y, Emura F, Matsuda T, et al: A new sinker-assisted endoscopic submucosal dissection for colorectal cancer. Gastrointest Endosc. 62:297–301. 2005. View Article : Google Scholar : PubMed/NCBI
36	Zhao J, Liao Q, Zhao Y and Hu Y: Mortality indicators and risk factors for intra-abdominal hypertension in severe acute pancreatitis. Int Surg. 99:252–257. 2014. View Article : Google Scholar : PubMed/NCBI
37	Vipperla K, Papachristou GI, Easler J, et al: Risk of and factors associated with readmission after a sentinel attack of acute pancreatitis. Clin Gastroenterol Hepatol. May 9–2014.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
38	Zeng YB, Zhan XB, Guo XR, et al: Risk factors for pancreatic infection in patients with severe acute pancreatitis: an analysis of 163 cases. J Dig Dis. 15:377–385. 2014. View Article : Google Scholar : PubMed/NCBI
39	Jin J, Yu YH, Zhong M and Zhang GW: Analyzing and identifying risk factors for acute pancreatitis with different etiologies in pregnancy. J Matern Fetal Neonatal Med. June 5;1–5. 2014.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
40	Tamasaki A, Nishimura Y, Kondo N, et al: Risk factors for acute pancreatitis in patients with severe motor and intellectual disabilities. Pediatr Int. 56:240–243. 2014. View Article : Google Scholar : PubMed/NCBI
41	Hong S, Qiwen B, Ying J, Wei A and Chaoyang T: Body mass index and the risk and prognosis of acute pancreatitis: a meta-analysis. Eur J Gastroenterol Hepatol. 23:1136–1143. 2011. View Article : Google Scholar : PubMed/NCBI
42	Shen HN, Wang WC, Lu CL and Li CY: Effects of gender on severity, management and outcome in acute biliary pancreatitis. PLoS One. 8:e575042013. View Article : Google Scholar : PubMed/NCBI
43	Fu P, Yuan AH, Wang CH, Li X and Wu HY: Alcohol-induced severe acute pancreatitis followed by hemolytic uremic syndrome managed with continuous renal replacement therapy. BMC Nephrol. 15:12014. View Article : Google Scholar : PubMed/NCBI
44	Nikkola J, Räty S, Laukkarinen J, et al: Abstinence after first acute alcohol-associated pancreatitis protects against recurrent pancreatitis and minimizes the risk of pancreatic dysfunction. Alcohol Alcohol. 48:483–486. 2013. View Article : Google Scholar : PubMed/NCBI
45	Müller S, Kaiser H, Krüger B, et al: Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice. PLoS One. 9:e944942014. View Article : Google Scholar : PubMed/NCBI
46	Okamura D, Starr ME, Lee EY, et al: Age-dependent vulnerability to experimental acute pancreatitis is associated with increased systemic inflammation and thrombosis. Aging Cell. 11:760–769. 2012. View Article : Google Scholar : PubMed/NCBI
47	Akesson A, Andersen LF, Kristjánsdóttir AG, et al: Health effects associated with foods characteristic of the Nordic diet: a systematic literature review. Food Nutr Res. 572013.
48	Overby NC, Sonestedt E, Laaksonen DE and Birgisdottir BE: Dietary fiber and the glycemic index: a background paper for the Nordic Nutrition Recommendations 2012. Food Nutr Res. 57:2013. View Article : Google Scholar : PubMed/NCBI
49	Knaan T, Endevelt R and Singer P: Evaluating the validity of the ‘categories method’: A new method for self-report assessment of daily calorie intake: A pilot study. Can J Diabetes. 37(Suppl 2): S2832013. View Article : Google Scholar
50	Pelaez-Luna M, Robles-Diaz G, Canizales-Quinteros S and Tusie-Luna MT: PRSS1 and SPINK1 mutations in idiopathic chronic and recurrent acute pancreatitis. World J Gastroenterol. 20:11788–11792. 2014. View Article : Google Scholar : PubMed/NCBI
51	Roncati L, Gualandri G, Fortuni G and Barbolini G: Sudden death and lipomatous infiltration of the heart involved by fat necrosis resulting from acute pancreatitis. Forensic Sci Int. 217:e19–e22. 2012. View Article : Google Scholar
52	Chen H, Li F, Jia JG, et al: Effects of traditional Chinese medicine on intestinal mucosal permeability in early phase of severe acute pancreatitis. Chin Med J (Engl). 123:1537–1542. 2010.
53	Zhang MJ, Zhang GL, Yuan WB, Ni J and Huang LF: Treatment of abdominal compartment syndrome in severe acute pancreatitis patients with traditional Chinese medicine. World J Gastroenterol. 14:3574–3578. 2008. View Article : Google Scholar : PubMed/NCBI
54	Athwal T, Huang W, Mukherjee R, et al: Expression of human cationic trypsinogen (PRSS1) in murine acinar cells promotes pancreatitis and apoptotic cell death. Cell Death Dis. 5:e11652014. View Article : Google Scholar : PubMed/NCBI
55	Wang J, Ohmuraya M, Suyama K, et al: Relationship of strain-dependent susceptibility to experimentally induced acute pancreatitis with regulation of Prss1 and Spink3 expression. Lab Invest. 90:654–664. 2010. View Article : Google Scholar : PubMed/NCBI
56	Corleto VD, Gambardella S, Gullotta F, et al: New PRSS1 and common CFTR mutations in a child with acute recurrent pancreatitis, could be considered an ‘Hereditary’ form of pancreatitis? BMC Gastroenterol. 10:1192010. View Article : Google Scholar
57	Ohmuraya M and Yamamura K: Roles of serine protease inhibitor Kazal type 1 (SPINK1) in pancreatic diseases. Exp Anim. 60:433–444. 2011. View Article : Google Scholar : PubMed/NCBI
58	Rai P, Sharma A, Gupta A and Aggarwal R: Frequency of SPINK1 N34S mutation in acute and recurrent acute pancreatitis. J Hepatobiliary Pancreat Sci. 21:663–668. 2014. View Article : Google Scholar : PubMed/NCBI
59	Tremblay K, Dubois-Bouchard C, Brisson D and Gaudet D: Association of CTRC and SPINK1 gene variants with recurrent hospitalizations for pancreatitis or acute abdominal pain in lipoprotein lipase deficiency. Front Genet. 5:902014. View Article : Google Scholar : PubMed/NCBI
60	Terlizzi V, De Gregorio F, Sepe A, et al: Brand new SPINK1 and CFTR mutations in a child with acute recurrent pancreatitis: a case report. Minerva Pediatr. 65:669–672. 2013.PubMed/NCBI
61	Jøergensen MT, Brusgaard K, Novovic S, et al: Is the SPINK1 variant p. N34S overrepresented in patients with acute pancreatitis? Eur J Gastroenterol Hepatol. 24:309–315. 2012. View Article : Google Scholar
62	Baudry C, Rebours V, Houillier P, et al: Recurrent acute pancreatitis caused by association of a novel mutation of the calcium-sensing receptor gene and a heterozygous mutation of the SPINK1 gene. Pancreas. 39:420–421. 2010. View Article : Google Scholar : PubMed/NCBI
63	Aoun E, Muddana V, Papachristou GI and Whitcomb DC: SPINK1 N34S is strongly associated with recurrent acute pancreatitis but is not a risk factor for the first or sentinel acute pancreatitis event. Am J Gastroenterol. 105:446–451. 2010. View Article : Google Scholar
64	Liu XB, Jiang JM, Huang ZW, et al: Clinical study on the treatment of severe acute pancreatitis by integrated traditional Chinese medicine and Western medicine. J Sichuan University (medical science edition). 35:204–208. 2004.(In Chinese).