青藤碱对肾移植大鼠静脉血IL-6的影响

背景：青藤碱具有镇静、镇痛、镇咳、抗心律失常、抗炎和免疫抑制等药理作用，近年来对其抗排斥作用的研究逐步深入。白细胞介素6是参与细胞介导移植物损伤的重要细胞因子，在诊断急性排斥反应及评价抗排斥反应的疗效方面具有重要的临床意义。 目的：通过检测青藤碱对肾移植受体鼠静脉血中白细胞介素6质量浓度的影响，分析青藤碱对大鼠肾移植后急性排斥反应的抑制作用以及与环孢素A是否存在协同效应。 设计、时间及地点：随机对照动物实验，于2008-03/2009-03在广州医学院第二附属医院外科实验室完成。 材料：选择近交系F344大鼠60只和近交系Wistar大鼠80只。 方法：建立近交系大鼠F344→Wistar肾移植动物模型48对，受体大鼠按照同期随机的原则分为4组，每组12只。生理盐水组给予生理盐水腹腔注射，1次/d；青藤碱组给予青藤碱腹腔注射，1次/d；环孢素A组给予环孢素A腹腔注射，1次/d；青藤碱+环孢素A组给予青藤碱+环孢素A腹腔注射，1次/d。以未做处理的Wistar大鼠12只为对照组。 主要观察指标：肾移植后第7天，应用酶联免疫吸附法检测受体大鼠静脉血白细胞介素6的质量浓度；完整留取移植肾行病理切片，观察病理改变，依据Banff标准对急性排斥反应病理改变进行分级评分。 结果：青藤碱组、环孢素A组、青藤碱+环孢素A组受体鼠的血白细胞介素6质量浓度均显著低于生理盐水组(P < 0.05)；青藤碱组与环孢素A组差异无显著性意义(P > 0.05)；青藤碱+环孢素A组显著低于青藤碱组、环孢素A组(P < 0.05)。病理切片按移植肾排斥反应组织学分级标准进行分级，生理盐水组3或4级；青藤碱组1或2级；环孢素A组1或2级；青藤碱+环孢素A组0或1级。 结论：青藤碱对同种异体大鼠肾移植急性排斥反应起到了较为确切的免疫抑制作用，能明显下调白细胞介素6的质量浓度，并与环孢素A存在协同作用。

Effects of alkaloid sinomenine on levels of IL-6 in vein blood of rat renal allograft models.

BACKGROUND: Alkaloid sinomenine has pharmacologic actions such as sedative, analgesia, relieving cough, arrhythmia resistance, anti-inflammatory and immunosuppression. Recently, its effect of anti-rejection has been explored. Interleukin-6 (IL-6) is an important factor that involved in cell-mediated graft injury. It has important clinical significance in the diagnosis of acute rejection and the evaluation of the efficacy of anti-rejection. OBJECTIVE: To evaluate the immunosuppressive efficacy and outcome of alkaloid sinomenine in acute refection after rat renal allograft and the synergistic effect in combination with Cyclosprin A (CsA) by monitoring the levels of IL-6 in venous blood. DESIGN, TIME AND SETTING: A randomized, controlled animal trial was performed at the Surgical Laboratory of Second Affiliated Hospital of Guangzhou Medical College between March 2008 and March 2009. MATERIALS: A total of 60 inbred F344 rats and 80Wistar rats were selected. METHODS: The acute rejection models were established with inbred F344 rats as donors and inbred Wistar rats as recipients; 48 recipients were randomly divided into 4 groups (n=12), and respectively intraperitoneally injected with normal saline, alkaloid sinomenine, CsA, and alkaloid sinomenine plus CsA, once daily. The remaining 12 Wistar rats were served as control. MAIN OUTCOME MEASURES: ELISA was used to test the levels of IL-6 quantitatively 7 days after transplantation. The transplanted kidneys were used to observe the pathological changes. According to the Banff criteria, the pathological changes in acute rejection after renal transplantation were graded. RESULTS: The levels of IL-6 in alkaloid sinomenine, CsA, and alkaloid sinomenine plus CsA were significantly less than normal saline group (P < 0.05), and no differences were found between alkaloid sinomenine and CsA groups (P > 0.05); the levels of IL-6 in alkaloid sinomenine plus CsA group was significantly less than alkaloid sinomenine and CsA groups (P < 0.05). With the Banff criteria of pathological changes in acute rejection after renal transplantation, normal saline group was grade 3 or 4, alkaloid sinomenine group grade 1 or 2, CsA group grade 1 or 2, and alkaloid sinomenine plus CsA group grade 0 or 1. CONCLUSION: Alkaloid sinomenine shows definite immunosuppressive effect and significantly reduced the level of IL-6 may be the immunosuppressive mechanism of sinomenine. Moreover, it has a synergistic effect in combination with CsA.