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目的研究小剂量FK778对大鼠移植肾慢性排斥反应的预防作用。方法应用显微外科技术制作大鼠移植肾慢性排斥反应模型;将肾移植后的大鼠分为两组。治疗组:将FK778溶解在羧甲基纤维素溶液中,行灌胃治疗,自术后第1天开始,每天1次,剂量为5mg·kg~(-1)·d~(-1),治疗至肾移植后24周。对照组:用单纯羧甲基纤维素溶液对大鼠行灌胃治疗,每天1次,直至移植后24周。移植后每4周测定1次24h尿蛋白含量,第24周时处死大鼠,对移植肾行组织学、免疫组织化学及实时定量逆转录聚合酶链(RT-PCR)检测。结果治疗组大鼠24h尿蛋白含量、肾组织病理损害程度、淋巴细胞和单核/巨噬细胞浸润程度与对照组比较均显著减低,肾组织生长因子TGF-β、PDGF-B基因的表达也显著减少。结论小剂量FK778能预防大鼠移植肾慢性排斥反应。
Objective To study the preventive effect of low dose FK778 on chronic rejection in rat renal allografts. Methods The rat model of chronic allograft rejection was established by microsurgical technique. The rats after renal transplantation were divided into two groups. Treatment group: FK778 was dissolved in carboxymethylcellulose solution and intragastric administration was given. The dosage of FK778 was 5 mg · kg -1 · d -1 since the first day after operation, once a day, Treatment until 24 weeks after kidney transplantation. Control group: Rats were treated with carboxymethylcellulose solution by gavage once daily until 24 weeks after transplantation. Urine protein content was measured once every 4 weeks after transplantation, and rats were sacrificed at the 24th week. Histology, immunohistochemistry and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were performed on the grafted kidney. Results The proteinuria of 24 h, pathological damage of renal tissue, infiltration of lymphocytes and monocytes / macrophages in the treatment group were significantly decreased compared with the control group, and the expression of TGF-β and PDGF-B Significantly reduced. Conclusion Low-dose FK778 can prevent chronic rejection in rat renal allografts.