血管内皮细胞生长因子及受体2在慢性砷中毒大鼠附睾中的表达

The expression of vascular endothelial cell growth factor and its receptor 2 in the epididymis of rats with chronic arsenic poisoning

目的探讨慢性砷中毒对大鼠附睾中血管内皮细胞生长因子（VEGF）及受体2（VEGFR2）表达和细胞凋亡情况的影响。方法选择健康清洁雄性SD大鼠40只，体质量为160～200g，采用随机数字表法将大鼠随机分为高[60．0mg／L亚砷酸钠（NaAs02）]、中（12．0mg／LNaA．s02）、低（2．4mg／LNaAs02）剂量组和对照组（蒸馏水），每组10只，采用经口自由饮用方式连续染砷6个月。染砷结束后处死动物。迅速分离附睾。采用TUNEL细胞凋亡染色法检测大鼠附睾上皮细胞凋亡情况，免疫组织化学法检测附睾中VEGF及VEGFR2的表达水平。结果对照组，低、中、高剂量组大鼠附睾体部上皮细胞凋亡（124．68±6．59、138．96±8．48、152．59士10．79、170．69±16．60）比较，差异有统计学意义（F=10．562，P〈0．05），随着染砷剂量的升高，凋亡细胞增多。对照组，低、中、高剂量组附睾体部、头部、尾部VEGF水平（148．50±0．60、134．20±0．85、98．23±0．80，136．70±0．95、128．20±0．72、90．30±0．12，127．80±0．62、117．60±0．72、84．51±0．60，120．26±0．46、90．12±0．36、66．43±0．90）比较，差异均有统计学意义（F=46．445、45．867、41．381，P均〈0．05），各染砷剂量组VEGF水平均低于对照组俨均〈0．05）。对照组，低、中、高剂量组头部、尾部VEGFIL2水平（130．70±0．89、128．80±0．70。126．30±0．65、121．42±0．62，120．26±0．12、117．84±0．55，102．60±0．78、104．92±1．15）比较，差异均有统计学意义（F=3．452、2．701，P均〈0．05），各染砷剂量组VEGFR2水平均低于对照组（P均〈0．05）。结论慢性砷中毒对大鼠附睾中VEGF及VEGFR2表达有抑制作用，引起附睾上皮细胞凋亡。与男性不育有一定的关系。

Objective To study the expression of vascular endothelial cell growth factor （VEGF） and its receptor 2 （VEGFR2） and apoptosis in the epididymis of rats with chronic arsenic poisoning. Methods Forty male Sprague-Dawley rats, weighting 160 - 200 g, were selected and randomly divided into four groups： high dose [60.0 mg/L sodium arsenite （NaAs02）], medium dose （12.0 mg/L Nahs02）, low dose arsenic infected groups （2.4 mg/L NaAsOz）, and control group （distilled water）. The rats were treated with arsenic through drinking water for 6 consecutive months. At the end of the experiment, all rats were killed and epididymis was separated rapidly, apoptosis cells of rat epididymis were determined via the TUNEL method, the expressions of VEGF and VEGFR2 were observed through immunohistochemistry. Results The apoptosis of the epididymis tubules epithelial cells were compared in control, low, medium, and high dose groups （124.68 ± 6.59, 138.96 ± 8.48, 152.59 ± 10.79, 170.69 ± 16.60）, the differences were statistically significant （F = 10.552, P 〈 0.05）, with increased exposure doses of arsenic, apoptosis cells were increased. VEGF expression levels of the body, head and tail in epididymis were compared in control, low, medium, and high dose groups （148.50 ± 0.60, 134.20 ± 0.85, 98.23 ± 0.80; 136.70 ± 0.95, 128.20 ± 0.72, 90.30 ± 0.12; 127.80 ± 0.62, 117.60 ± 0.72, 84.51 ± 0.60; 120.26 ± 0.46, 90.12 ± 0.36, 66.43 ± 0.90）, the differences were statistically significant （F = 46.445, 45.867, 41.381, P 〈 0.05）, and VEGF expression levels in arsenic infected groups were lower than that in control group （P 〈 0.05）; VEGFR2 expression levels of the head and tail （130.70 ± 0.89, 128.80 ± 0.70; 126.30 ± 0.65, 121.42 ± 0.62; 120.26 ± 0.12, 117.84 ± 0.55; 102.60 ± 0.78, 104.92 ± 1.15） were compared, the differences were statistically significant （F = 3.452, 2.701, P 〈 0.05）, and VEGFR2 expression levels in arsenic infected groups were lower than that in control group （P 〈 0.05）. Conclusion Arsenism has inhibitory effect on the expression of VEGF and VEGFR2 in the epididymis, leading to epididymis epithelial cell apoptosis, which indicates it may play an important role in male infertility.