顺铂诱发大鼠睾丸毒性的机制及葡萄籽原花青素的防护作用

Mechanism of cis-Diamminedichloroplatinum-Induced Testicular Toxicity and Protective Effect of Grape Seed Proanthocyanidin Extract in Rats

目的:探究葡萄籽原花青素(grape seed proanthocyanidin extracts,GSPE)对顺铂(cisdiamminedichloroplatinum,CDDP)诱发大鼠睾丸氧化损伤和细胞凋亡的防护作用。方法:将40只大鼠随机分为空白对照组、CDDP模型组、GSPE低剂量组(200 mg/(kg·d))、GSPE高剂量组(400 mg/(kg·d))。分别以蒸馏水和相应剂量的GSPE对大鼠连续灌胃15 d,灌胃10 d后一次性腹腔注射CDDP,剂量为7 mg/kg,空白对照组注射相同剂量的生理盐水。注射CDDP后第5天处死大鼠,检测精子指标、大鼠睾丸组织中超氧化物歧化酶(superoxide dismutase,SOD)与谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活力、还原型谷胱甘肽(glutathione,GSH)与丙二醛(malondialdehyde,MDA)含量,流式细胞仪检测大鼠睾丸细胞凋亡率,并观察睾丸组织在光镜下形态的变化。结果:CDDP模型组大鼠睾丸和附睾的质量、附睾精子的浓度和活动度、GSH-Px、SOD活力以及GSH含量均显著降低,而MDA水平和睾丸细胞凋亡率显著升高。预防性口服GSPE显著改善了CDDP引起的大鼠睾丸质量减小、功能减弱以及氧化应激、脂质过氧化和细胞凋亡这些不利影响。结论:GSPE对CDDP诱发的大鼠睾丸毒性有剂量依赖性防护作用,其机制很可能与抑制体内氧化应激及细胞凋亡有密切关系。

Objective： To investigate the possible protective role of grape seed proanthocyanidin extract （GSPE） on cis- diamminedichloroplatinum （CDDP）-induced spermiotoxicity. Methods： A total of 40 rats were randomly divided into 4 groups： blank control group, CDDP model group, and low-dose GSPE ＋ CDDP group, high-dose GSPE ＋ CDDP group （orally administered at doses of 200 mg/（kg·d） and 400 mg/（kg·d）, respectively, daily for 15 days）, each group containing ten rats. After 10 days of administration, the blank control group was given normal saline by intraperitoneal injection, while a single intraperitoneal injection of CDDP （7 mg/kg） was carded out in the remaining groups. At the end of the administration period, all rats were sacrificed to determine testicular and epididymal weights, epididymal sperm count and motility, GSH-Px and SOD activities, and GSH contents. Apoptosis rates of testieular cells were tested by flow cytometer, and histopathological characteristics were observed under a microscope. Results： Testicular and epididymal weights, epididymal sperm count and motility, GSH-Px and SOD activities, and GSH levels were significantly decreased whereas the level of MDA and apoptosis rates were significantly increased in rats from the CDDP group. GSPE treatment significantly attenuated the CDDP-induced loss of testicular and epididymal weights and the dysfunction of reproductive organs, oxidative stress, lipid peroxidation and cell apoptosis. Conclusion： GSPE has a dose-dependent protective effect against CDDP-induced testicular toxicity in rats. This protective effect seems to be closely associated with the suppression of oxidative stress and cell apoptosis.