雷抑素对大鼠移植肝Kupffer细胞的影响

Effect of leflunomide pretreatment on Kupffer cells in transplanted rat liver

目的探讨肝移植术前应用雷抑素对大鼠肝Ｋｕｐｆｅｒ细胞的影响方法以ＳＤ大鼠为供受体建立原位肝移植模型．受体移植术前３ｄ连续口服１％羧甲基纤维素１ｍｌ／ｄ（对照组）或雷抑素１０ｍｇ／ｋｇ·ｄ（用药组）．分别于术后１，２，３，２４ｈ采血并取肝组织，检测血清ＴＮＦ，ＡＬＴ及肝ＭＤＡ水平，观察肝超微结构及大鼠１周存活率变化．结果对照组移植术后３ｈ血清ＴＮＦ（５３ｋＵ／Ｌ±０４１ｋＵ／Ｌ），肝ＭＤＡ（４８４６ｎｍｏｌ／ｇ±２３６ｎｍｏｌ／ｇ）显著增加，ＴＮＦ表达呈强阳性；而且药组ＴＮＦ（０９ｋＵ／Ｌ±０１１ｋＵ／Ｌ）肝ＭＤＡ（３６１８ｎｍｏｌ／ｇ±１５４ｎｍｏｌ／ｇ）无明显变化，ＴＮＦ表达阴性，两者相差显著Ｐ＜００１）．电镜检查，对照组肝Ｋｕｐｆｅｒ细胞呈活化表现，而用药组肝Ｋｕｐｆｅｒ细胞呈非活化状态．对照及用药组术后１周存活率分别为０％和６０％．结论术前应用雷抑素可抑制移植肝ＴＮＦ和Ｏ２的产生，抑制Ｋｕｐｆｆｅｒ细胞活化，以减轻肝冷缺血再灌注损伤．

AIM To study the effect of leflunomide on rat liver Kupffer cells before liver transplantion. METHODS SD rats were used as donors and recipients to build orthotopic liver transplantation models. The recipient rats were pretreated by a 3 day course of 1% carboxymethylcellulose (1ml/day, PO) in control group or leflunomide (10mg/kg·d, PO) in treatment group. Blood and liver samples were taken at 1, 2, 3 and 24 hours respectively after transplantation. Levels of TNF and ALT in serum, and MDA in liver tissues were measured, ultrastructure of liver and one week survival rates observed. RESULTS The levels of serum TNF (5 3kU/L±0 41kU/L) and MDA in liver tissues (484 6nmol/g±23 6nmol/g) increased rapidly, and TNF expression was strongly positive 3 hours after transplantation in control group. The Lef pretreated recipients had little changes in serum TNF levels (0 9kU/L±0 11kU/L) and MDA in liver tissues (361 8nmol/g±15 4nmol/g), and TNF expression was negative, with a significant difference between the two groups ( P <0 01). The Kupffer cells from controls were activated in appearance, while those from pretreated group showed no evidence of activation under electron microscope. One week survival rates for control and treatment groups were 0% and 60%, respectively. CONCLUSION Leflunomide pretreatment can suppress TNF and O 2 production and the activation of Kupffer cells in liver transplantation model, thus minimizing cold ischemic reperfusion injury.