评估实验性环孢素毒性对雄性生殖和肾功能的影响。同时给予人绒毛膜促性腺激素的逆转作用。

Evaluation of the effect of experimental cyclosporine toxicity on male reproduction and renal function. Reversal by concomitant human chorionic gonadotropin administration.

作者信息

Seethalakshmi L, Flores C, Khauli R B, Diamond D A, Menon M

机构信息

Division of Urologic Transplantation and Surgery, University of Massachusetts Medical Center, Worcester 01655.

出版信息

Transplantation. 1990 Jan;49(1):17-9. doi: 10.1097/00007890-199001000-00004.

DOI:10.1097/00007890-199001000-00004

PMID:2301008

Abstract

Administration of cyclosporine to rats has been shown to impair testicular function, resulting in a decrease in sperm counts and fertility. In order to determine whether or not the deleterious effects of CsA could be reversed by hormonal therapy, mature male Sprague Dawley rats were treated with CsA (40 mg/kg/day, s.c.) alone or in combination with human chorionic gonadotropin (hCG) (5 micrograms/day/r; s.c.) for 14 days. Cyclosporine administration decreased the body weight (290 +/- 5.30 vs. 339 +/- 8.7 g; P less than 0.05) and reproductive organ weights (testis 1.49 +/- 0.42 vs. 1.60 +/- 0.03 g; epididymis 0.41 +/- 0.02 vs. 0.49 +/- 0.002 g; seminal vesicle 0.61 +/- 0.09 vs. 1.60 +/- 0.05 g; prostate 0.28 +/- 0.04 vs. 0.60 +/- 0.06 g; P less than 0.05) testicular sperm counts (5.80 +/- 0.42 vs. 8.49 +/- 0.48 x 10(7)/100 mg tissue; P less than 0.05) and epididymal sperm counts, (28.2 +/- 0.95 vs. 51 51.62 +/- 2.17 x 10(7)/100 mg tissue; P less than 0.05) and fertility (25% vs. 100%). Serum levels of LH were elevated (101.98 +/- 21.48 vs. 25.6 +/- 5.18 ng/ml; P less than 0.05) and testosterone was decreased (0.48 +/- 0.07 vs. 2.06 +/- 0.56 ng/ml; P less than 0.05). The administration of hCG to the CsA-treated rats restored the reproductive organ weights (testis 1.56 +/- 0.043 g; seminal vesicle 1.04 +/- 0.05 g; prostate 0.70 +/- 0.06 g) and sperm counts (testicular 7.88 +/- 1.0 x 10(7)/100 mg tissue; epididymal 59.86 +/- 4.16 x 10(7)/100 mg tissue; P less than 0.05) Serum levels of testosterone (18.63 +/- 4.45 ng/ml) and LH (431.65 +/- 31.41 ng/ml) were significantly elevated, as compared with control and CsA-treated groups (P less than 0.05). All the rats in the gonadotropin-treated group were fertile, as compared with 25% in the CsA-treated group. CsA reduced the kidney weight (1.17 +/- 0.02 vs. 1.27 +/- 0.03 g; P less than 0.05) and increased the levels of serum creatinine (0.97 +/- 0.07 vs. 0.59 +/- 0.03 mg/dl; P less than 0.05): these changes were ameliorated by the administration of hCG (kidney weight 1.35 +/- 0.03 g; creatinine 0.76 +/- 0.09 mg/dl).

摘要

已证明给大鼠施用环孢素会损害睾丸功能，导致精子数量和生育能力下降。为了确定激素疗法是否可以逆转环孢素A的有害作用，将成熟雄性Sprague Dawley大鼠单独用环孢素A（40mg/kg/天，皮下注射）或与人类绒毛膜促性腺激素（hCG）（5微克/天/只；皮下注射）联合治疗14天。施用环孢素A会降低体重（290±5.30对339±8.7g；P<0.05）和生殖器官重量（睾丸1.49±0.42对1.60±0.03g；附睾0.41±0.02对0.49±0.002g；精囊0.61±0.09对1.60±0.05g；前列腺0.28±0.04对0.60±0.06g；P<0.05）、睾丸精子数量（5.80±0.42对8.49±0.48×10⁷/100mg组织；P<0.05）和附睾精子数量（28.2±0.95对51.62±2.17×10⁷/100mg组织；P<0.05）以及生育能力（25%对100%）。血清促黄体生成素（LH）水平升高（101.98±21.48对25.6±5.18ng/ml；P<0.05），睾酮水平降低（0.48±0.07对2.06±0.56ng/ml；P<0.05）。给环孢素A处理的大鼠施用hCG可恢复生殖器官重量（睾丸1.5 < 0.043g；精囊1.04±0.05g；前列腺0.70±0.06g）和精子数量（睾丸7.88±1.0×10⁷/100mg组织；附睾59.86±4.16×10⁷/100mg组织；P<0.05）。与对照组和环孢素A处理组相比，血清睾酮（18.63±4.45ng/ml）和LH（431.65±31.41ng/ml）水平显著升高（P<0.05）。与环孢素A处理组的25%相比，促性腺激素处理组的所有大鼠都具有生育能力。环孢素A降低了肾脏重量（1.17±0.02对1.27±0.03g；P<0.05）并提高了血清肌酐水平（0.97±0.07对0.59±0.03mg/dl；P<0.05）：这些变化通过施用hCG得到改善（肾脏重量1.35±0.03g；肌酐0.76±0.09mg/dl）。