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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。
BACKGROUND: Sinomenine has pharmacological effects such as sedation, analgesia, antitussive, anti-arrhythmia, anti-inflammatory and immunosuppressive. In recent years, its research on anti-rejection has gradually deepened. Interleukin-6 is an important cytokine involved in cell-mediated graft injury and has important clinical significance in diagnosing acute rejection and evaluating the efficacy of anti-rejection. Objective: To detect the effect of sinomenine on the interleukin-6 concentration in rat venous blood of kidney transplant recipients, and to analyze the inhibitory effect of sinomenine on acute rejection after renal transplantation in rats and whether there is synergy with cyclosporine A. effect. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at the Surgical Laboratory of the Second Affiliated Hospital of Guangzhou Medical College from March 2008 to March 2009. MATERIALS: A total of 60 inbred F344 rats and 80 inbred Wistar rats were selected. METHODS: Forty-eight pairs of F344->Wistar renal allograft models were established in inbred rats. Recipient rats were divided into 4 groups according to the principle of randomization over the same period, 12 in each group. The saline group was given intraperitoneally with normal saline once a day; the sinomenine group was given sinomenine intraperitoneally once a day; the cyclosporine A group was given intraperitoneally with cyclosporine A, once a day; The base + cyclosporine A group was given intraperitoneally with sinomenine and cyclosporine A once daily. 12 untreated Wistar rats served as controls. MAIN OUTCOME MEASURES: On the 7th day after kidney transplantation, the concentration of interleukin-6 in venous blood of the recipient rats was detected by enzyme-linked immunosorbent assay; the transplanted kidneys were harvested and pathological sections were taken for observing the pathological changes, according to the Banff criteria for acute Rejection pathological changes were graded. RESULTS: The serum interleukin-6 concentration in rats receiving sinomenine, cyclosporine A, and sinomenine + cyclosporine A was significantly lower than that of saline (P<0.05); sinomenine There was no significant difference between cyclosporine A group and sinomenine group and cyclosporine A group (P>0.05). Pathological sections were graded according to the histological grading criteria of renal allograft rejection, normal saline group 3 or 4; sinomenine group 1 or 2; cyclosporine A group 1 or 2; sinomenine + cyclosporine A group 0 or 1 level. Conclusion: Sinomenine has a more effective immunosuppressive effect on acute allograft rejection in renal allograft rats. It can significantly down-regulate interleukin-6 concentration and has a synergistic effect with cyclosporine A.