~ Insulin-like Growth Factor-I~ oa ~

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^Abstract =

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~ Insulin-like Growth Factor-I~ oa ~

Bile Duct Ligation and Insulin-like Growth Factor-I on the Ischemia-Reperfusion Injury of the Smail Bowel

Je-:Sun Cha, M.D., Myung Duk Lee, M.D.

Pediatric Surgery, Department of SUTgeTY, Catholic University Medical College Seoul, Korea

To determine whether bile juice exclusion can prevent the mucosal damage, and Insulin-like growth factor-I can promote mucosal regeneration in ische- mia-reperfusion injury of the bowel, 39 weanling rats with 10 cm of Thiry-Vella loop were studied. Animal groups were; Control, BL(common bile duct ligation), IGF{insulin-like growth factor-I(IGF-I) infusion} and IGF-BL( combined treat- ment). IGF-I(1.5 mg/kg/day) was continuously delivered through a subcutaneously implanted miniosmotic pump. After 15 minutes of superior mesenteric artery clamping, a tissue specimen(P) was taken after 30 minutes of reperfusion. Intes- tinal continuity was restored to allow oral feeding. A specimen of main tract(M) and another of the Thiry-Vella 100p(T) were collected for histomorphometry after 48 hours of reperfusion and free feeding. Villus size ratio(VSR), crypt depth(CD), crypt-depth/villus-height ratio(CVR) and injury score(IS) were mea- sured in 15 consecutive villi. The postoperative mortalities of bile duct ligation groups(BL and IGF-BL) were higher than those of other groups. In control group, VSR of M was lower(P<0.05) than P or T, but not in the other groups.

VSR of M in conrol was lower than those in other groups. CD of T in control, IGF and IGF-BL group were higher than those of M. CD of M and T showed gradual increaments from control, IGF and IGF-BL group, respectively. CVR of M and T in IGF group were higher than those in: control. CVR in IGF-BL group, T was higher than M, and M was higher than P. About IS, M of BL(20.

1 ± 2.5) and IGF-BL(20.9 ± 3.3) groups were significantly lower than that of controI(32,4 ± 2.5). These results suggest that the exclusion of bile juice reduces the severity of the reperfusion injury of the mucosa, by inability to activate pancreatic enzymes and IGF-I stimulates mucosal regeneration in injured bowel, and the effect is potentiated by bile juice exclusion.

Index Words: Ischemia-reperjusion injury, IGF-I, Small Intestine, Bilfrduct ligation

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Table 1. Operative Survival Rates

Group No. of total animal No. of survivor Survival rate(%)

C 8 7 87.5

BL 11 7 63.6

IGF 9 8 88.9

IGF-BL 11 8 72.7

Abbreviations: C; control, BL; bile duct ligation, IG F; IG F-I infusion, JG F-BL; IG F-I infusion and bile duct ligation

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~ III Q)

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Control BL IGF IGF-BL

Experimental Group

Fig. 2. Histogram of villus size ratio( C: control group, BL: bile duct ligation, IG F: IG F-l infusion, IG F-B L: IG F-1 infusion and bile duct ligation).

*: p < 0.01 between P-tract and M -tract in control group.

t :

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+ : ^p < 0.05 between M -tract of control group and that of IG F-B L group.

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c Q)

Q.

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Control

Fig. 3. Histogram of crypt depth.

BL IGF

Experimental Group

* : p < 0.001 between M -tract of control and that of IG F group.

t : p < 0.001 between T-tract of control and that of IGF group.

IGF-BL

+ :

p < 0.05 between M -tract of IG F group and that of IG F-BL group.

n:p < 0.05 between T-tract'of IGF grouP and that oflGF-BL group.

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a

Control BL IGF

Experimental Group

Fig. 4. Histogram of CVR.

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t :

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IGF~BL

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Fig. 5. Histogram of injury score.

BL IGF

Experimental Group

*: p < 0.001 between M -tract of control and that of BL group.

t :

p < 0.001 between M -tract of control and that of IGF-BL group.

I

IGF-BL

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l. Granger DN, Rutili G, McCord JM: Super- oxide radicals in feline intestinal ischemia.- Gastroenterology 81: 22-29, 1981

2. Parks DA, Bulkley GB, Granger DN, Ha- milton SR, McCord JM: Ischemic injury in cat small intestine; role of superoxide rad- icals. Gastroenterology 82: 9-15, 1982 3. Parks DA, Bulkeley GB, Granger DN: Role

of oxygen free radicals in shock, ischemia and organ preservation. Surgery 94 :428- 432, 1983

4. Dalsing MC, Grosfelt JL, Shiffler MA, Vane DW, Hull M, Baehner RL, Weber TR: S uperoxide dismutase: a cellular pro- tective enzyme in bowel ischemia. J Surg Res 34:589-596, 1903

5. Rijke ,RPC, Hanson WR, Plaisier HM, 'Os bone JW: The effectrs of ischemic villus cell damage on crypt cell proliferation in the small intestine. Gastroenterology 76:

786-792, 1976

6. Menge H, Robinson JWG: Early phase of jejunal regeneration after short ischemia in the rat. Lab Invest 40:25-30, 1979 7. ;t}

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46(1):159-165,1993

8. Lee MD, Lee S, Kim SN, Kim IC: The ef- fects of bowel content on ischemic injury of the small, intestine. Transplant Proceed 24:1073-1076,1992

9. Steenfos HH: Growth factors and wound healing. Scand J Plast " Reconstr Hand

Surg 2895-105, 1994

10 Vanderhoof JA, McCusker RH, Clark R, Mohammadeour H, Blackwood DJ, Harty RF, Park JHY: Truncated and native in- sulin like Growth Factor I enhance muco- sal adaptation after jejunoileal resection.

Gastroenterology 102: 1949-1956, 1992 11 Lacy ER, Ito S: Microscopic analysis of

ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroen- terology 83: 619-625, 1982

12. Alza phan:naceuticals: Alzet^R osmotic pumps surgical implantation techniques. Video tape, ALZA corporation, 1995, Palo Alto, CA, 94303-0802

13. Chaet MS, Arya G, Ziegler MM, Warner BW: Epidermal growth factor enhances in- testinal adaptation after massive small bowel resection. J Pediatr Surg 29: 1035- 1039, 1994

14. Cueva' JP, Hsueh W: Role of oxygen de- rived free radicals in platelet activating factor induced bowel necrosis. Gut 29:

1207-1212, 1988

15. Winser J, Green D, Ferrell L, Renner 1:

Evidence for a role of oxygen derived free radicals in the pathogenesis of caerulein in- duced acute pancreatitis in rats. Gut 29:

1516-1523, 1988

16. Ross RJM, Rodriguez-Arnao J, Bentham J, Coakley JH: The role of insulin, growth hormone and IGF-I as anabolic agents in the critically ill. Intensive Care M ed 19:

S54-S57, 1993

17. Clemmons DR, Smith-Banks A, Under- wood LE: Reversal of diet-induced catabo- lism by infusion of recombinant Insu- lin-like growth factor-I in humans. J Clin Endocrinol M etab 75: 234-238, 1992 18. Inaba T, Saito H, Fukushima R, Hashi-

guchi Y, Lin MT, Inoue T, Fukatsu K, Muto T, Oka T, Takenaka A, Takahashi

S, Noguchi T: Insulin-like growth factor-I has beneficial effects, whereas growth ~or­

mone has limited effects on postoperative protein metabolism, gut integrity, and splenic weight in rats with chronic mild liver injury JPEN 21 :55-62, 1997

19. Chen K, Okuma T, Okamura K, Tabira Y, Kaneko H, Miyauchi Y: Insulin-like growth factor-I prevents gut atrophy and main- tains intestinal integrity in septic rats.

JPEN 19:119-124, 1995

20. Byrne TA, Persinger RL, Young LS, Ziegler TR, Wilmore DW: A new treatment for patients with short-bowel syndrome. Growth hormone, glutamine and a modified diet.

Ann Surg 222 :243-254, 1995

21 Donovan SM, Zijlstra RT, Odie J: Use of the piglet to study the role of ·growth fac- tors in neonatal intestinal development.

Endoc Reg 28(4):153-162 1994

22. Zhang W, Frankel WL, Adamson WT, Roth JA, Mantell MP, Bain A, Ziegler TR, Smith RJ, Rombeau JL: Insulin-like growth factor-I improves mucosal struc- ture and function in transplanted rat small intestine. Transplantation 59 (5) : 755- 761, 1995

23. Steeb CB, Trahair JF, Tomas FM, Read IC; Prolonged administration of IG F pep- tides enhances growth of gastroitestinal tissues in normal rats. Am J Physiol 266:

G 1090-G 1098, 1994

24. Guzman C, MaCleod RJ, Hamilton JR:

Failure of ornithin decarboxylase inhibition to alter small intestinal epithelial repair after transient segmental ischemia. Gut 29 : 935-940, 1988

25. Steeb CB, Trahair JF, Read LC: admini- stration of insulin-like growth factor-I (IG F-I) peptides for three days stimulates proliferation of the small intestinal epitheli- um in rats. Gut 37:630-638, 1995