Effect of Pravastatin on the Survival of Islet Xenografts_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WEI Zhengqiang , YAO Zhengxiang , HUANG Ping , DONG Pujiang , YANG Guanglun

Department of General Surgery, The First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400016, China;

Corresponding author：

Keywords：

pravastatin; Macrophage; Islet xenografts

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Objective To study the effect of pravastatin on the survival of islet xenografts.MethodsPigtomouse islet transplantation was performed. The models were divided into 4 groups: group A (control); group B, treated with CsA; group C, treated with pravastatin; group D, treatment with combined CsA with pravastatin. The survival time (ST) of the grafts in each group were recorded. Histological examination was used to detect the inflammation and islet cells in the graft. The infiltrated cells were detected by immunohistochemistry with CD4+, CD8+ and CD68 monoclonal antibody. The serum NO was measured. RTPCR was used in the test of IFNγ mRNA.ResultsThe ST of group A,B,C,D was (6.2±0.82) d, (9.2±1.92) d, (7.2±1.30) d, (11.2±1.76) d respectively, the ST of group D was much longer than that of the other groups (P＜0.05).Compared to that in other groups, less infiltrated cell in group D was found. On the 4th postoperative day, the serum NO in group A was (105.0±19.3) mmol/L,significantly higher than that in group B 〔(88.20±21.04) mmol/L〕, in group C 〔(70.7±17.8) mmol/L)〕　and in group D 〔(56.30±16.4) mmol/L〕. When rejection occurred, the serum NO in group C and D was (83.7±10.6) mmol/L and (71.3±13.8) mmol/L, also lower than that in group A (P＜0.05), the serum NO in group B was (104.7±16.3) mmol/L, compared that in group A, no significance was present (P gt;0.05）. On the 4th postoperative day, the serum expression of IFNγ mRNA in group D was 23.5±4.6, lower than that in group A (28.8±4.8), and no significance was present compared with that in group B and C. ConclusionPravastatin can abate the role of macrophages, especially combined with Cyclosporine, and can prolong the survival of islet xenograft.

Citation： WEI Zhengqiang,YAO Zhengxiang,HUANG Ping,DONG Pujiang,YANG Guanglun. Effect of Pravastatin on the Survival of Islet Xenografts. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2003, 10(2): 121-124. doi: Copy

1.	Nagata M, Mullen Y, Matsuo S, et al. Destruction of islet isografts by severe nonspecific inflammation [Ｊ]. Transplant Proc, 1990; 22(2)∶855.
2.	Kaufman DB, Platt JL, Rabe FL, et al. Differential roles of Mac1+cells, and CD4+ and CD8+ T lymphocytes in primary nonfunction and classic rejection of islet allografts [Ｊ]. J Exp Med, 1990; 172(1)∶291.
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4.	Kroncke KD, KolbBachofen V, Berschick B, et al. Activated macrophages kill pancreatic syngeneic islet cells via argininedependent nitric oxide generation [Ｊ]. Biochem Biophys Res Commun, 1991; 175(3)∶752.
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6.	Katznelson S, Wilkinson AH,Kobashigawa JA, et al. The effect of pravastatin on acute rejection after kidney transplantationa pilot study [Ｊ]. Transplantation, 1996; 61(10)∶1469.
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1. Nagata M, Mullen Y, Matsuo S, et al. Destruction of islet isografts by severe nonspecific inflammation [Ｊ]. Transplant Proc, 1990; 22(2)∶855.
2. Kaufman DB, Platt JL, Rabe FL, et al. Differential roles of Mac1+cells, and CD4+ and CD8+ T lymphocytes in primary nonfunction and classic rejection of islet allografts [Ｊ]. J Exp Med, 1990; 172(1)∶291.
3. Pukel C, Baquerizo H, Rabinovitch A. Destruction of rat islet cell monolayers by cytokines. Synergistic interactions of interferongamma, tumor necrosis factor, lymphotoxin, and interleukin 1 [Ｊ]. Diabetes, 1988; 37(1)∶133.
4. Kroncke KD, KolbBachofen V, Berschick B, et al. Activated macrophages kill pancreatic syngeneic islet cells via argininedependent nitric oxide generation [Ｊ]. Biochem Biophys Res Commun, 1991; 175(3)∶752.
5. Arita S, Une S, Ohtsuka S, et al. Prevention of primary islet isograft nonfunction in mice with pravastatin [Ｊ]. Transplantation, 1998; 65(11)∶1429.
6. Katznelson S, Wilkinson AH,Kobashigawa JA, et al. The effect of pravastatin on acute rejection after kidney transplantationa pilot study [Ｊ]. Transplantation, 1996; 61(10)∶1469.
7. Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation [Ｊ]. N Engl J Med, 1995; 333(10)∶621.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Pravastatin on the Survival of Islet Xenografts

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