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目的观察肾移植术后不同免疫抑制剂的首剂治疗剂量对独肾模型大鼠睾丸发育及精子质量的影响。方法按公式将肾移植术后患者的环孢素A(cyclosporin A,CsA)、他克莫司(tacrolimus,FK506)和雷帕霉素(rapamycin,Rapa)的首剂治疗剂量换算为大鼠的用药剂量。构建大鼠独肾模型,将建模成功的32只大鼠随机分为4组,分别为对照组、CsA[25 mg/(kg.d)]组、FK506[0.8 mg/(kg.d)]组和Rapa[0.2 mg/(kg.d)]组,每组8只。胃饲8周后处死大鼠,称取睾丸重量,并计算睾丸脏器系数;制作睾丸组织匀浆悬液,精子计数,观察精子活率及畸形率;HE染色观察每组睾丸病理改变。结果 CsA组大鼠的双侧睾丸重量[(2.63±0.57)g]明显少于其他各组大鼠(P<0.05);CsA组及Rapa组大鼠睾丸脏器系数、精子数量、精子活率低于对照组及FK506组(P<0.05);各实验组精子畸形率高于对照组(P<0.05),其中CsA组最为明显(P<0.001);镜下观察:各实验组均有不同程度的病理学改变,表现为曲细精管管腔缩小、稀疏、生精细胞层数减少、腔内精子减少、部分曲精小管出现空泡样变,间质细胞萎缩、水肿、出血等。其中CsA组病理改变最为明显,FK506组曲细精管结构基本完整,仅部分分布稍稀疏,Rapa组大鼠部分曲细精管萎缩。结论肾移植术后不同免疫抑制剂的首剂治疗剂量对大鼠睾丸发育及精子质量均有不同程度的影响;与CsA和Rapa相比,FK506引起的睾丸和精子病变最为轻微。
Objective To observe the effect of the first dose of different immunosuppressive agents after kidney transplantation on the development of testis and sperm quality in the kidney of the kidney. Methods According to the formula, the first dose of cyclosporin A (CsA), tacrolimus (FK506) and rapamycin (Rapa) in patients after renal transplantation was converted into rats Dose. Thirty-two rats were randomly divided into four groups: control group, CsA [25 mg / (kg · d)] group, FK506 [0.8 mg / (kg · d) ] Group and Rapa [0.2 mg / (kg.d)] group, 8 in each group. The rats were killed after 8 weeks of stomach feeding, the weight of testis was weighed and the testicular organ coefficient was calculated. The suspension of testis tissue was made, the sperm count was counted, the sperm motility and the rate of deformity were observed. The pathological changes of testis were observed by HE staining. Results The testicular weight, sperm count and sperm motility in CsA group and Rapa group were significantly lower than those in other groups ([2.63 ± 0.57] g] (P <0.05). The sperm deformity rate in each experimental group was higher than that in control group (P <0.05), especially in CsA group (P <0.001). Microscopic observation: The experimental groups were all different The degree of pathological changes, manifested as seminiferous tubules narrow, sparse, sperm cell layer decreased, reduced intracavitary sperm, vacuole-like part of the seminiferous tubules, interstitial atrophy, edema, bleeding and so on. Among them, the pathological changes of CsA group were the most obvious. The seminiferous tubules of FK506 group were basically intact, only slightly sparsely distributed, and part of the seminiferous tubules of Rapa group were atrophied. Conclusion The first dose of different immunosuppressive agents after kidney transplantation has different effects on testicular development and sperm quality in rats. Compared with CsA and Rapa, FK506 causes the least testicular and sperm lesions.