南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (2): 251-256.doi: 10.12122/j.issn.1673-4254.2023.02.13

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棉酚短期给药对小鼠的生殖毒性和肾毒性具有可逆性

王 辉，朴智燕，马 慧，曹琳育，刘 俊，武军驻   

  1. 武汉大学基础医学实验教学中心，口腔医学院，湖北 武汉 430071
  • 出版日期:2023-02-20 发布日期:2023-03-16

Short-term exposure to gossypol causes reversible reproductive toxicity and nephrotoxicity in mice

WANG Hui, PIAO Zhiyan, MA Hui, CAO Linyu, LIU Jun, WU Junzhu   

  1. Demonstration Center for Experimental Basic Medicine Education, School of Stomatology, Wuhan University, Wuhan 430071, China
  • Online:2023-02-20 Published:2023-03-16

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摘要： 目的 研究棉酚短期给药对小鼠睾丸和肾脏的影响，同时探究该影响是否具有可逆性。方法 将20只7~8周雄性小鼠随机分成4组：空白对照组、溶剂对照组、棉酚给药组和停药组，分别给与纯化水、1%羧甲基纤维素钠水溶液、30 mg/mL棉酚溶液和30 mg/mL棉酚溶液，每只小鼠每天灌胃1次，0.3 mL/次，连续灌胃14 d后。将空白对照组、溶剂对照组、棉酚给药组小鼠处死，取组织样本；停药组小鼠停止给药，纯化水灌胃14 d后处死，取组织样本。睾丸组织进行称重、HE染色和PAS染色；肾脏组织进行HE染色和线粒体ATPase活力检测。结果 与对照组相比，棉酚给药组小鼠睾丸生精上皮层细胞的数量明显减少，生精小管变圆，生精小管之间空隙明显变大，睾丸间质萎缩，精原细胞分化不完全，无长形精子细胞，大量细胞处于圆形精子细胞状态，顶体PAS反应阴性。肾脏弥漫性系膜细胞增生，系膜基质增多，与肾小囊壁层粘连，肾小囊腔明显缩小甚至消失；肾脏线粒体ATPase活力降低（P<0.001）。停药组与棉酚给药组相比，睾丸和肾脏形态结构、顶体PAS反应及线粒体ATPase活力均有不同程度的恢复。结论 棉酚短期给药处理后出现生殖毒性和肾毒性，停药后一段时间症状得到恢复，具有可逆性。

关键词: 棉酚；睾丸；顶体；肾毒性；ATPase；可逆性

Abstract: Objective To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible. Methods Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity. Results Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity. Conclusions Short-term treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.

Key words: gossypol; testis; acrosome; nephrotoxicity; ATPase; reversibility