环孢素对大鼠同种胚胎后肾移植的影响

Effect of ciclosporin A on the organogenesis and function of embryonic metanephroi allografted into adult rats

目的探讨环孢素对胚胎后肾在同种异体成年大鼠体内生长发育及功能发挥的影响。方法将实验组60只行单侧肾脏切除的成年SD大鼠按照使用CsA与否以及移植不同时期(孕后第15、16、17天,E15、E16、E17)的胚胎后肾随机分为6组(E15CsASD、E16CsASD、E17CsASDE15SD、E16SD、E17SD),每组10只,对照组30只SD大鼠同法分组,每组5只,宿主肾脏不切除。Lewis大鼠E15后肾移植到行单侧肾脏切除的成年BN大鼠大网膜(E15CsABN和E15BN),按照使用环孢素与否分为2组,每组15只。术后首日起,使用环孢素组受体大鼠以环孢素8mg·kg-1·d-1皮下注射;不使用环孢素组以等量的生理盐水皮下注射。移植后2～4周开腹观察器官形成情况,并进行组织病理学和后肾功能检查。结果(1)移植后28d,E16SD、E17SD组出现不同程度的排斥反应。E16CsASD、E17CsASD组后肾发育良好、无排斥反应;停用CsA后,原先发育良好的E16CsASD、E17CsASD后肾出现排斥反应。(2)移植后28d,E15SD后肾发育良好,无排斥反应,到100d检查时,发生排斥反应;移植后2周,E15BN组后肾即被完全排斥,而E15CsABN组后肾发育完好。E15CsABN组停用CsA后,原先发育完好的后肾被排斥。(3)移植时宿主肾脏不切除而植入后肾,其后肾不发育。(4)E15CsASD组移植后肾湿重、体积均小于E15SD组(分别为t=-3.

Objective To evaluate the effect of ciclosporin A (CsA) on the organogenesis and function of embryonic metanephroi allografted into adult rats. Methods The whole metanephroi from the 15, 16 and 17 embryonic day-old (E15, E16, E17) embryos of Sprague-Dawley (SD) rat were allografted into the omenta of SD adult rats with their left kidneys resected, which were divided into 2 categories: ~3 CsA- treated groups of 10 rats (E15CsASD, E16CsASD, and E17CsASD) and 3 non-CsA-treated groups of 10 rats (E15SD, E16SD, and E17SD). Thirty SD rats without kidney resection were divided into 6 equal groups and underwent allografting embryonic metanephroi in the same manner as mentioned above. The E15 metanephroi of Lewis rats were allografted into the omenta of Thirty adult Brown Norway(BN) rats with one kidney resected. Were divided into 6 equal groups, received allografting of embryonic metanephroi, and injected with CsA of normal saline in the manner as mentioned above (E15CsABN and E15BN). Two to 4 weeks after implantation, the metanephroi allografted in host rats were removed for histopathological examination or anastomosed for renal function measurement 4 weeks later. Results (1) Four weeks after implantation, the E17SD and E16SD metanephroi showed signs of acute rejection as hypercellular glomeruli and mononuclear cell infiltration in the interstitium. The E16CsASD and E17CsASD metanephroi formed mature nephrons and collecting ducts with few lymphocytic infiltrates. After CsA was discontinued, the E16CsASD and E17CsASD metanephroi were rejected fully within 21 days. (2) 4 weeks after implantation, the E15SD metanephroi were enlarged, became vascularized, and developed mature tubules and glomeruli; however, they were rejected by 100 days after implantation. The E15 Lewis metanephroi were fully rejected within two weeks in the BN adult rats. With CsA administrated, the E15 Lewis metanephroi developed normal mature nephrons and collecting ducts within the adult BN rats. If CsA was discontinued, the E15CsABN metanephroi were rejected. (3) The E15CsASD metanephroi had significantly lower values of wet weight (P=0.006) and higher values of creatinine clearances (P=0.007) than the E15SD metanephros transplants, but were identical to those of the E16CsASD metanephroi (P=0.948, ~P=0.840 ). (4) The metanephroi did not grow or differentiate in the rats without host kidney resection. Conclusions (1) Cyclosporin A may suppress graft rejection, thus normalizing the growth and function of fetal metanephroi in the omenta of host rats. (2) A variety of factors affect the growth and development of allografted metanephroi, whereas rejection remains the major one.