美洛昔康对铝过负荷致雄鼠生殖损害的保护作用

Meloxicam protects aluminum overload-induced chronic reproductive deterioration in rats

目的探讨COX-2抑制剂美洛昔康对慢性铝过负荷所致雄性大鼠生殖损害的保护作用。方法雄性大鼠分为5组,每组6只,即正常对照组、铝负荷组[葡萄糖酸铝Al3+200 mg/(kg.d)灌胃]、美洛昔康组[美洛昔康3 mg/(kg.d)灌胃]、铝负荷+小剂量美洛昔康组[葡萄糖酸铝Al3+200 mg/(kg.d)+美洛昔康1 mg/(kg.d)灌胃]及铝负荷+大剂量美洛昔康组[葡萄糖酸铝Al3+200 mg/(kg.d)+美洛昔康3 mg/(kg.d)灌胃]。每周给药5 d,连续20周后处死大鼠取出睾丸附睾称质量,分别计算每只大鼠睾丸、附睾系数(脏器质量/体质量);HE染色观察睾丸附睾的形态学变化。结果正常对照组、美洛昔康组、铝负荷组、铝负荷+小剂量美洛昔康组、铝负荷+大剂量美洛昔康组大鼠体质量均值分别是572.2、568.8、451.8、552.3、565.7 g,睾丸质量均值分别是4.92、4.91、4.07、4.65、4.86 g,附睾质量均值分别是1.36、1.33、1.12、1.25、1.32 g,铝负荷组大鼠的体质量、睾丸及附睾质量明显降低(P<0.05),美洛昔康组、铝负荷+大剂量美洛昔康组与正常对照组比较无显著差异(P>0.05),铝负荷+小剂量美洛昔康组大鼠体质量降低无显著意义(P>0.05),但睾丸附睾质量降低具有显著差异(P<0.05),5组间睾丸附睾系数无显著性差异(P>0.05)。HE染色见铝负荷组曲细精管的生精上皮明显变薄且几乎看不到精细胞、在曲细精管腔内精子数量很少或没有;铝负荷+大剂量美洛昔康组在曲细精管内见大量的各级精细胞及精子;美洛昔康组见睾丸的组织学形态完全正常。铝负荷组大鼠睾丸组织COX-2蛋白表达明显增加(P<0.05);美洛昔康可明显抑制COX-2蛋白表达,大剂量美洛昔康(3 mg/kg)组抑制效应更明显(P<0.05)。结论 美洛昔康具有改善铝所致的生殖损害的潜能;其机制可能与抑制COX-2活性,减轻炎症反应和氧化应激损伤有关。

Objective To determine the protective effects of meloxicam on deterioration in reproductive performance induced by chronic aluminum overload in rats.Methods A total of 30 Wistar male rats were randomly and equally divided into 5 groups,normal control,aluminum gluconate group,meloxicam group,aluminum gluconate plus low-and high-dose meloxicam groups.Aluminum gluconate was intragastrically administered at 200 mg Al^3＋/（kg·day）,and meloxicam was given with same way in 30 min after aluminum administration at 1 or 3 mg/（kg·day）.Rats of each group were administrated in 5 d every week for 20 weeks.After which,all rats were killed,and their testis and epididymis were dissected out and weighted for calculating their organic coefficient.Morphologic changes of testis were evaluated by HE staining.Expression of COX-2 was detected by Western blotting.Results The weights of body,testis and epididymis in the aluminum gluconate group was significantly lower compared with those of the other 4 groups（P〉0.05）.There was no significant difference in these values among meloxicam group,aluminum gluconate plus high-dose meloxicam groups and control（P〉0.05）.Though no difference was seen in body weight between the aluminum gluconate group and the aluminum gluconate plus low-dose meloxicam groups（P〉0.05）,obvious difference was found in the weights of testis and epididymis（P〈0.05）.There was no obvious difference in the testis and epididymis coefficients（P〉0.05）.HE staining showed that the germinal epithelium of the seminiferous tubules became obviously thinner and spermatids were almost absent;sperms were rare or absent in the lumen in the the aluminum gluconate group.But in the high-dose meloxicam group,there were large numbers of spermatids and sperms in the seminiferous tubule lumen.Normal structure and morphology was found in the meloxicam group,as the control group.Meloxicam obviously inhibited the over-expression of COX-2,especially when it was at high dose（P〉0.05）.Conclusion Meloxicam has protective effects on reproductive deterioration induced by chronic aluminum overload in rats,which may be through inhibiting COX-2 activity and attenuating the inflammation and oxidative stress injury.