Effect of TLSFJM Associated with Small Dose of FK506 on The Immunosuppression in Rat Small Bowel Transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DONG Guanglong ¹ , L I Kaizong ¹ , WANG Weizhong ¹ , ZHANG Zhang ¹ , CHEN Lihua ² , JIN Boquan ²

1. Department of Gastrointestinal Surgery , Xijing Hospital ;;
2. Department of Immunology ;;
The Fourth Military Medical University , Xi’an 710032 , China;

Corresponding author：

Keywords：

TLSFJM,　Small bowel transplantation,　Rejection,　FK506

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Objective 　To investigate the inhibitory effect and its mechanisms of TLSFJM (JM acute T leukemia cell line derived suppressor factor) on allograf t rejection of small bowel t ransplantation in rat , and to compare the effect s and complications of TLSFJM with those of FK506. Methods 　One hundred male Brown Norway (BN) rats and 100 Lewis
(L EW) rat s were t reated as donors and recipient s of small bowel t ransplantation , respectively. Then they were divided into five groups according to the dose of administ ration of TLSFJM and/ or FK506 : small bowel transplantation group (SBT group) ; large dose of FK506 〔0. 5 mg/ ( kg ·d) 〕group ; small dose of FK506 〔0. 25 mg/ (kg ·d) 〕group ; TLSFJM 〔10 U/ ( kg ·d) 〕group ; TL SFJM 〔10 U/ ( kg ·d) 〕associated with small dose of FK506 〔0. 25 mg/ (kg ·d) 〕group. FK506 and TLSFJM were administered through int ramuscular or int raperitoneal injection , respectively. Survival time , body weight , hepatic and renal function and histopathology of recipient s in each group were observed. Results 　TLSFJM took no damage effect on the recipient s’renal and hepatic functions 7 days after administ ration. When TLSFJM was administ rated associated with small dose of FK506 in small bowel transplantation , it could not only effectively suppress rejection reaction , extend recipient’s survival time , but also decreased the dosage of FK506 and prevented the side effect s. But TLSFJM may not be used as immunosuppressive agent alone for the prevention and treatment of rejection in rat small bowel t ransplantation because the rejection still existed. Conclusion 　As an effective immunosuppression agent , TLSFJM associated with small dose of FK506 can prolong the survival time of both recipients and graf ting small bowel , relieve intensity of rejection , and prevent the side effect s when high dosage FK506 is administ rated. TLSFJM may be used as a high-efficiency , low-toxicity immunosuppresive agent in small bowel transplantation.

Citation： DONG Guanglong ,L I Kaizong,WANG Weizhong,ZHANG Zhang,CHEN Lihua,JIN Boquan. Effect of TLSFJM Associated with Small Dose of FK506 on The Immunosuppression in Rat Small Bowel Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(1): 41-45. doi: Copy

1.	<>[1]Tzakis AG,Nery JR,Thompson J,et al.New immunosuppressive regimens in clinical intestinal transplantation[J].Transplant Proc,1997; 29(1-2)∶683.
2.	Fung JJ,Starzl TE.FK506 in solid organ transplantation[J].Transplant Proc,1994; 26(5)∶3017.
3.	Guo WH,Tian L,Dallmann MJ,et al.Comparative study of allograft survival of heterotopic and orthotopic small bowel transplantation in rat[J].Transplantation,2003; 75(11)∶1895.
4.	Higuchi K,Kimura O,Furukawa T,et al.FK506 induces the atrophy of enteric ganglia in small bowel transplantation,which can be prevented by the neuropeptide bombesin[J].Transplant Proc,2006; 38(6)∶1823.
5.	董光龙,李开宗,王为忠.双Cuff双造口大鼠异位小肠移植模型的建立[J].第四军医大学学报,2003; 24(2)∶189.
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8.	Jiang H,Kobayashi M.Differences between cyclosporin A and tacrolimus in organ transplantation[J].Transplant Proc,1999; 31(5)∶1978.
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11.	申立中,金伯泉,夏海滨,等.TLSFJM对DNFB诱导的小鼠接触性皮炎和同种异体皮片移植排斥反应的抑制作用[J].细胞与分子免疫学杂志,1996; 12(4)∶27.
12.	韩卫宁,李德敏,苏丽,等.TLSFJM对同种异体抗原诱导的小鼠杀伤性T细胞分化及效应功能的影响[J].细胞与分子免疫学杂志,1999; 15(2)∶118.
13.	Guo WH,Tian L,Chan KL,et al.Role of CD4+ and CD8+ T cells in early and late acute rejection of small bowel allograft[J].J Pediatr Surg,2001; 36(2)∶352.
14.	Ma H,Wang J,Wang J,et al.Features of chronic allograft rejection on rat small intestine transplantation[J].Pediatr Transplant,2007; 11(2)∶165.
15.	Song J,Ito T,Matsuda C,et al.Regulation of donor T cells in the tolerant rats to graft-versus-host disease by FTY720 following small bowel transplantation[J].Transplant Proc,2006; 38(10)∶3181.
16.	Gasser M,Otto C,Timmermann W,et al.Putative regulatory function of alloreactive Th2 cells in tolerant recipients after small bowel transplantation[J].Transplant Proc,2001; 33(1-2)∶161.
17.	智星,严律南,杨培,等.CTLA4-Ig抗大鼠肝移植排斥反应及诱导免疫耐受的实验研究[J].中国普外基础与临床杂志,2005; 12(6)∶600.
18.	董光龙,李开宗,王为忠.TLSFJM对小肠移植大鼠外周血及移植肠浸润淋巴细胞的影响[J].免疫学杂志,2003; 19(1)∶36.

1. <>[1]Tzakis AG,Nery JR,Thompson J,et al.New immunosuppressive regimens in clinical intestinal transplantation[J].Transplant Proc,1997; 29(1-2)∶683.
2. Fung JJ,Starzl TE.FK506 in solid organ transplantation[J].Transplant Proc,1994; 26(5)∶3017.
3. Guo WH,Tian L,Dallmann MJ,et al.Comparative study of allograft survival of heterotopic and orthotopic small bowel transplantation in rat[J].Transplantation,2003; 75(11)∶1895.
4. Higuchi K,Kimura O,Furukawa T,et al.FK506 induces the atrophy of enteric ganglia in small bowel transplantation,which can be prevented by the neuropeptide bombesin[J].Transplant Proc,2006; 38(6)∶1823.
5. 董光龙,李开宗,王为忠.双Cuff双造口大鼠异位小肠移植模型的建立[J].第四军医大学学报,2003; 24(2)∶189.
6. Grant D.Current results of intestinal transplantation.The International Intestinal Transplant Registry[J].Lancet,1996; 347(9018)∶1801.
7. 魏晓平,李立.他克莫司与环孢素A在器官移植中的应用比较[J].中国普外基础与临床杂志,2003; 10(4)∶415.
8. Jiang H,Kobayashi M.Differences between cyclosporin A and tacrolimus in organ transplantation[J].Transplant Proc,1999; 31(5)∶1978.
9. Miyauchi T,Ishikawa M,Tashiro S,et al.Effect of donor-specific splenocytes via portal vein and FK506 in rat small bowel transplantation[J].Transplantation,1998; 65(1)∶27.
10. 金伯泉.一株人急性淋巴细胞白血病细胞所分泌抑制因子的免疫调节作用[J].中华血液学杂志,1990; 11(5)∶247.
11. 申立中,金伯泉,夏海滨,等.TLSFJM对DNFB诱导的小鼠接触性皮炎和同种异体皮片移植排斥反应的抑制作用[J].细胞与分子免疫学杂志,1996; 12(4)∶27.
12. 韩卫宁,李德敏,苏丽,等.TLSFJM对同种异体抗原诱导的小鼠杀伤性T细胞分化及效应功能的影响[J].细胞与分子免疫学杂志,1999; 15(2)∶118.
13. Guo WH,Tian L,Chan KL,et al.Role of CD4+ and CD8+ T cells in early and late acute rejection of small bowel allograft[J].J Pediatr Surg,2001; 36(2)∶352.
14. Ma H,Wang J,Wang J,et al.Features of chronic allograft rejection on rat small intestine transplantation[J].Pediatr Transplant,2007; 11(2)∶165.
15. Song J,Ito T,Matsuda C,et al.Regulation of donor T cells in the tolerant rats to graft-versus-host disease by FTY720 following small bowel transplantation[J].Transplant Proc,2006; 38(10)∶3181.
16. Gasser M,Otto C,Timmermann W,et al.Putative regulatory function of alloreactive Th2 cells in tolerant recipients after small bowel transplantation[J].Transplant Proc,2001; 33(1-2)∶161.
17. 智星,严律南,杨培,等.CTLA4-Ig抗大鼠肝移植排斥反应及诱导免疫耐受的实验研究[J].中国普外基础与临床杂志,2005; 12(6)∶600.
18. 董光龙,李开宗,王为忠.TLSFJM对小肠移植大鼠外周血及移植肠浸润淋巴细胞的影响[J].免疫学杂志,2003; 19(1)∶36.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of TLSFJM Associated with Small Dose of FK506 on The Immunosuppression in Rat Small Bowel Transplantation

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