茯苓素预防大鼠肾移植急性排斥反应的实验研究

Preventive Effect of Poria cocos on Acute Rejection of Renal Transplantation in Rats

目的探讨茯苓素(Poria cocos)预防大鼠肾脏移植急性排斥反应的作用和机制。方法以Wist-ar大鼠为供者,SD大鼠为受者,建立原位(腹腔)肾脏移植模型,移植前按照分组分别以生理盐水、茯苓素25mg.kg-1.d-1、茯苓素50 mg.kg-1.d-1和环孢素A(CsA)5 mg.kg-1.d-1灌胃。术后观察大鼠移植肾功能和存活时间,测定各组术后1周外周血中白细胞介素2(IL-2)和γ干扰素(IFN-γ)含量以及CD4+、CD8+细胞百分比和CD4+/CD8+的比值,并观察移植肾的病理变化。结果茯苓素50 mg.kg-1.d-1组和CsA组移植肾和受者存活时间较茯苓素25 mg.kg-1.d-1组和生理盐水组显著延长(P<0.05),而且病理损害程度较茯苓素25 mg.kg-1.d-1组和生理盐水组明显减轻,但茯苓素50 mg.kg-1.d-1组较CsA组移植肾存活时间显著减少(P<0.05)。各组移植肾功能和尿量变化与存活时间和移植肾病理变化相一致,茯苓素50 mg.kg-1.d-1组和CsA组肾功能异常发生时间明显晚于茯苓素25 mg.kg-1.d-1组和生理盐水组。茯苓素50 mg.kg-1.d-1组外周血IL-2和IFN-γ的含量较茯苓素25 mg.kg-1.d-1组和生理盐水组显著降低(P<0.01),但显著高于CsA组(P<0.01);茯苓素50 mg.kg-1.d-1组外周血CD4+细胞百分比显著低于茯苓素25 mg.kg-1.d-1组(P<0.05)和生理盐水组(P<0.01),CD8+细胞百分比显著低于生理盐水组(P<0.05)。结论茯苓素对肾脏移植急性排斥反应有较好的抑制作用且与剂量呈正相关,但效果不如CsA。

Objective To study the effect of Poria cocos （Pcs） in preventing acute rejection of rats after renal transplantation and its mechanism. Methods Rat orthotopic renal transplantation model was performed with Wistar rat as donor and SD rat as donee. All donees were divided into 4 groups, 10 in each group, before transplantation. They were treated respectively with normal saline 5 mL ·kg^-1·d^-1 （A）, Pcs 25 mg·kg^-1·d^-1 （B）, Pcs 50 mg ·kg^-1·d^-1 （C） and ciclosporin A （CsA） 5 mg·kg^-1·d^-1（D） by intragastric administration. The renal allograft survival time （ST） was recorded, and the serum levels of creatinine （SCr）, intedeukin-2 （ IL- 2）, y-interferon （y-IFN）, CD4 , CD8＋ lymphocytes percentage, CD4＋/CD8＋ratio, as well as the pathologic changes were observed one week after transplantation. Results ST of the renal graft in Groups C and D was significantly longer with pathologic change evidently less than those in Groups A and B （ P 〈 0. 01 ）, and the ST in Group C was shorter that in Group D （P 〈0.05）. Changes of renal function and urine volume were identified to the pathological change of graft, the initiating time of renal dysfunction was later in Groups C and D than that in Groups A and B. Serum levels of IL-2, IFN-y and CD4 percentage in Group C were significantly lower than those in Groups A and B, but higher than those in Group D respectively （ P 〈 0.05 or P 〈 0.01 ）, while CD8＋ percentage in Group C was significantly lower than that in Group A （P 〈0.05）, but insignificantly different to that in Groups B and D （ P 〉0. 05）. Conclusion Pcs shows good dosage-dependent effect in suppressing acute rejection of renal transplantation, but the effect is inferior to that of CsA.