Expressions of leptin, COX22 and p27 in bile2induced gastric mucosa injury

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1 ( ) J ournal of Xiπan J iaot ong U niversity (Medical Sciences) V ol. 29 No. 5 Oct p27, (, ) : (leptin) 22 (COX22) p27 SD 4 : (duodenogastric reflux, D GR) D GR + (bile duct ligation, BDL) (BDL) (control, C) 12,, DIX2 ON ; (SP) COX22 p27 DIXON D GR D GR + BDL BDL ( P < 0. 05),D GR D GR + BDL DIXON ( P < 0. 05) ;D GR D GR + BDL BDL COX22 ( P < 0. 05),p27 ( P < 0. 05),D GR D GR + BDL ( P < 0. 05) DIXON COX22, p27, COX22 p27 : ; ; ;COX22 ;p27 :R33 :A : (2008) Expressions of leptin, COX22 and p27 in bile2induced gastric mucosa injury Song Yinxue, Gong J un (Depart ment of Gastroenterology, t he Second Affiliated Hospital, Medical School of Xiπan Jiaotong University, Xiπan , China) ABSTRACT : Objective To explore t he role of lep tin, CO X22 and p27 in bile2induced gast ric mucosal injury in rats. Methods SD rats were divided int o 4 groups : D GR (duodenogast ric reflux) group, D GR + BDL (ligation of bile duct) group, BDL group and cont rol group. The p at hological changes of gast ric mucosa and tight junction were observed, D I XON scores were warked out af ter 3 mont hs. Immunohist ochemist ry was used t o detect t he exp ression of lep tin, CO X22 and p27 in gast ric mucosa wit h different lesions. Re sults The D I XON scores in D GR and D GR + BDL group were higher t han t hose in BDL group and cont rol group ( P < 0. 05). In addition, D I XON scores were higher in D GR group t han in D GR + BDL group ( P < 0. 05). The exp ressions of lep tin and CO X22 increased in D GR group and D GR + BDL group t han in BDL group and cont rol group ( P < 0. 05), w hile p27 decreasd ( P < 0. 05). D GR group was more notable t han D GR + BDL group ( P < 0. 05). The exp ression of lep tin a nd CO X22 was p ositively correlated wit h D I XON integral, but negatively related t o p27. Conclusion L ep tin, CO X22 and p27 are all concerned wit h renovating p at hological changes in bile2induced gast ric mucosal injury in rats. KEY WORDS : bile ; gast ric mucosal ; lep tin ; CO X22 ; p27 [ 1 ] PGE2, bcl22 COX22 p27, JA K/ STAT MAPK : : : (No ) : (19722), ( ),,. :. E2mail : com, [2 ] ;COX22,,, [3 ] ;p27, cyclin2cd K CD Ks,, [4 ] SD, (leptin) 22 (COX22) p27,

2 514 ( ) SD 40,, g, 6/ 0 leptin (bs20108r), p27 ( SC21641) COX22 Ig G ( SC21746) SP ( SP29003 SP29002) 1. 2 SD 4 (integrated opti2 ( duodenogastric reflux, D GR) (10 ) : [5 ] ( Treitz 4cm,, Treitz ; (bile duct ligation, BDL ) (10 ) : [ 6 ] (,, ) ;D GR + BDL (10 ) : D GR + BDL ; C : (,10 ) :,, 12,, XDJ2IA p H p H, ( TBA) 1. 3 H E SD ( ) 4-6,, H E, : DIXON [7 ], :, (0-3 ) ; (0-3 ) ; (0-3 ),, 1/ 2 1-3, 0, (0-3 ), (0-3 ), 1. 4 COX22 p27 40 ml/ L,, SP DGR + BDL, COX22 p ,, PBS : COX22,,,,p27 [5 ], ( - ), < 25 % ( + ), 25 % - 50 % ( 6 ), > 50 % ( 7 ) ( 100) 5, ( 200) Image2pro plus6. 0, cal density, IOD) 1. 5 SPSS 15. 0, (One2Way ANOVA), F ( F ), L SD, P < 0. 05, P < Pearson, ( R), P < p H 1 1 p H Table 2 p H of gastric juice and TBA of serum in the groups Group p H TBA D GR D GR + BDL BDL C ( n = 10) P < vs. cont rol group, P < vs. D GR group D GR : duodenogastric reflux group ; D GR + BDL : duodenogastric reflux plus ligation of bile duct group ; BDL : ligation of bile duct group ; C : control group 2. 2 H E DGR,,,,,, 1/ 3, BDL DIXON DGR DGR + BDL BDL, ( P < 0. 05), DGR DGR +

3 5,. 22 p BDL, ( P < 0. 05),BDL ( P > 0. 05, 2) 2. 3 COX22 p27 BDL 2/ 3,DGR DGR + BDL,, ; COX22 BDL ;p27 BDL, 2/ 3, DGR DGR + BDL BDL p27,dgr DGR + BDL BDL, ( P < 0. 05) ;D GR + BDL BDL, ( P > 0. 05) ;BDL ( P > 0. 05) COX22 DGR DGR + BDL BDL, ( P < 0. 05) ;DGR DGR + BDL, ( P < 0. 05) ;BDL ( P > 0. 05) p27 DGR DGR + BDL BDL, ( P < 0. 05) ;DGR + BDL BDL, ( P > 0. 05) ;BDL D GR D GR + BDL ( P > 0. 05) ( 2, 1-3) 2 DIXON COX22 p27 Table 2 DIXON scores and IOD of leptin, COX22 and p27 in the group s ( n = 10) Group DIXON scores Leptin ( 10 5 ) COX22 ( 10 5 ) p27 ( 10 5 ) D GR D GR + BDL BDL C P < vs. control group, P < vs. D GR group 1 Fig. 1 The expression of leptin in rat gastric mucosa (SP 200) A : D GR group ( 7 ) ; B : D GR + BDL group ( 6 ) ; C : BDL group ( + ) ; D : control group ( + ) 2. 4 DIXON ( r = , P < 0. 05) ;DIXON COX22 ( r = , P < 0. 05) ;DIXON p27 ( r = , P < 0. 05) ;p27 COX22 ( r = , P < 0. 05) ; p27 ( r = , P < 0. 05) ; COX22 ( r = , P < 0. 05) 3, [8 ],,,, [9 ],,

4 516 ( ) 29 [10 ], J A K2STA T, T [ 2 ],, D GR (D GR, ) (D GR + BDL, ), ( leptin ) 22 (COX22) p27 12 p H p H D GR D GR + BDL,,,,,D GR + BDL BDL D GR, ; D GR,,, D GR D GR + BDL,, 2/ 3, [8 ] D GR D GR + BDL,, 2/ 3, D GR D GR + BDL, DIXON ( P < 0. 05),, COX22,,,,,, COX22, Gudis [11 ] COX22, ( HCF)

5 5,. 22 p ( V EGF), COX22, Schmassmann [12 ] COX22, COX22, BDL COX22, COX22,COX22,D GR D GR + BDL,DIXON COX22 ( P < 0. 05), COX22 p27kip1 [4 ],,p27,,p27,, HP, (cyclin dependent kinase inhibitors, CD KI) p27, (cyclin dependent kinases, C KIs), p27, [ 13 ] BDL p27 2/ 3, [4 ] ;D GR D GR + BDL p27, p27, D GR D GR + BDL, ( P < 0. 05),DIXON p27 ( P < 0. 05),, p27, p27, : [ 1 ] Mabrut J Y, Collard J M, Baulieux J. Duodenogast ric a nd gas2 troesop hageal bile reflux [J ]. J Chir, 2006, 143 (6) : [ 2 ]Schneider R, Bornstein SR, Chrousos GP, et al. L eptin medi2 ates a prolif erative response in human gastric mucosa cells with f unctional recept or [J ]. Hor m Metab Res, 2001, 33 (1) :126. [ 3 ]Oba M, Miwa K, Fujimura T, et al. Chemop revention of glan2 dular stomach carcinogenesis t hrough duodenogastric reflux in rats by a CO X22 inhibitor [ J ]. I nt J Cancer, 2008, 123 ( 7) : [ 4 ] Chu I, Sun J, Ar naout A, et al. p27 Phosp horylation by Src regulates inhibition of cyclin E2Cdk2 [J ]. Cell, 2007, 128 (2) : [ 5 ],,,. CyclinD1 p16 [J ]., 2004, 21 (5) : [ 6 ],,,. [J ]. ( ), 2006, 37 (5) : [ 7 ] Dixon M F, Neville PM, Mapstone N P, et al. Bile reflux gastri2 tis a nd Barrett s oesop hagus : f urt her evidence of a role f or duod2 enogast ro2oesop hageal reflux [J ]? Gut, 2001, 49 (3) : [ 8 ] Ca mmisotto PG, Gingras D, Renaud C, et al. Secretion of sol2 uble leptin receptors by exocrine and endocrine cells of the gas2 tric mucosa [ J ]. A m J Physiol2Gastrointest Liver Physiol, 2006, 290 (2) : G2422G249. [ 9 ] Konturek PC, Brzozowski T, Sulekova Z, et al. Role of leptin in ulcer healing [J ]. Eur J Phar macol, 2001, 414 (11) : [ 10 ] Erkasap N, Uzuner K, Serteser M, et al. Gastroprotective eff ect of leptin on gastric mucosal injury induced by ischemia2 reperf usion is related to gastric hista mine content in rats [ J ]. Peptides, 2003, 24 (8) : [ 11 ] Gudis K, Saka moto C. The role of cyclooxygenase22 in gastric mucosal p rotection [J ]. Dig Dis Sci, 2005, 50 (1) :S162S23. [ 12 ]Schmassmann A, Zoidl G, Peskar BM, et al. Role of t he dif2 f erent isof or ms of cyclooxygenase and nitric oxide synthase dur2 ing gastric ulcer healing in cyclooxygenase21 a nd22 knockout mice [J ]. A m J Physiol2Gastrointest Liver Physiol, 2006, 290 (4) : G [ 13 ]Sung S K, Patricia M, Ta ma ko A K, et al. Altered exp ression of Skp2,c2Myc and p27 proteins but not mrna af ter H. pylori e2 radication in chronic gastritis [ J ]. Modern Pathol, 2006, 19 (1) : ( )