不同剂量外源性睾酮对去势雄兔动脉粥样硬化的影响

Effects of different levels of exogenous testosterone on atherosclerosis in castrated rabbits

目的探讨不同剂量的外源性睾酮对高胆固醇饲料饲养的去势(双侧睾丸切除)雄兔血清性激素、血脂、载脂蛋白水平以及动脉粥样硬化(AS)程度的影响。方法成熟雄性新西兰白兔35只,随机分成为假手术组、单纯去势安慰剂组、低剂量睾酮补充组(3mg/kg)、生理水平睾酮补充组(6mg/kg)和高剂量睾酮补充组(12mg/kg),每组7只。术前1周和术后第16周采血,测量血清总睾酮(TT)、雌二醇(E_2)、脱氢表雄酮(DHEA)及总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、载脂蛋白A_1(ApoA_1)、载脂蛋白B(ApoB)水平。计算AS指数(AI)。16周末处死动物,测量主动脉胆固醇含量,观察主动脉病理形态改变,测量血管内膜和中膜的厚度和比值。结果雄兔去势和去势后补充不同剂量睾酮,分别形成严重睾酮缺乏症及低睾酮血症、生理性睾酮血症和高睾酮血症。单纯去势安慰剂组,低剂量睾酮补充组和高剂量睾酮补充组的血清TC,TG,LDL-C和ApoB水平及LDL-C/HDL-C,AI和ApoB/ApoA_1均明显高于生理睾酮组和假手术组(P<0.01)。雄兔补充睾酮后,单纯去势安慰剂组、低剂量睾酮补充组和高剂量睾酮补充组的主动脉胆固醇含量最高,分别是(75.8±5.9),(76.3±6.1)和(75.2±2.3)mmol/g蛋白,组间相比较无显著差异(P>0.05),为生理剂量睾酮补充组水平的2.5倍(P<0.01)。生理剂量睾酮补充组的主动脉胆固醇含量最低,相当于假手术组的2/3[(21.0±5.6)vs(30.9±8.4)mmol/g,P<0.01]。单纯去势安慰剂组、低剂量睾酮补充组和高剂量睾酮补充组的主动脉血管内膜/中膜比分别为(0.65±0.21),(0.62±0.24)和(0.65±0.25),组间相比较无显著差异(P>0.05),均明显大于假手术组(0.31±0.07)(P<0.01)。生理剂量睾酮补充组的血管内膜/中膜比最小(0.26±0.08),明显低于假手术组(P<0.01)。结论外源性生理剂量的睾酮能改善高脂饲养的去势雄兔血脂、脂蛋白和载脂蛋白异常,外源性高和低剂量睾酮均不能改善血脂、脂蛋白和载脂蛋白的异常,且在抗AS方面无益。

Objective To explore the effects of different levels of exogenous testosterone on atherosclerosis,sex hormone, blood lipid and apolipoprotein in castrated rabbits.Methods Thirty-five male New Zealand white rabbits were randomly divided into sham operation group,placebo group,hypotestosteronemia group（3 mg/kg）,physitestosteronemia group（6mg/kg）, hypertestosteronemia group（12 mg/kg）,with 7 in each group.Total testosterone（TT）,estradiol（E_2）,dehydroepian-drosterone （DHEA） lipids,total cholesterol（TC）,high density lipoprotein cholesterol（HDL-C）,low density lipoprotein cholesterol（LDL-C）,triglyceride（TG）,apolipoprotein A_1（ApoA_1）,and apolipoprotein B（ApoB） were tested at 1 week before operation and 16 weeks after operation respectively.Atherosclerosis index（AI） was obtained（AI=（TC - HDL-C/HDL-C）.After 16 weeks,the aorta was observed morphometrically and immunohistologically,and the aortic cholesterol content was examined.Results Average serum lipids,atherogenic lipoproteins and apolipoproteins were significantly higher in placebo group,hypoteststeronemia and hypertestosteronemia groups than in sham operation group and physitestosteronemia group （P 0.01）.The aortic cholesterol content was（75.8±5.9）,（76.3±6.1） and（75.2±2.3）mmol/g protein respectively in placebo group,hypoteststeronemia group and hypertestosteronemia group,with no significant difference between the three groups（P 0.05）,which was 2.5 times of that of physitestosteronemia group[（21.0±5.6）mmol/g protein].The aortic cholesterol content was （21.0±5.6） and（30.9±8.4） mmol/g respectively in physitestosteronemia group and sham operation group（P 0.01）.The ratio of intima/tunica media was（0.65±0.21）,（0.62±0.24） and（0.65±0.25） respectively in placebo group,hypoteststeronemia group and hypertestosteronemia group respectively,with no significant difference between the groups（P 0.05）,which was higher obviously than that in sham operation group[（0.31±0.07）,P0.01].It was the lowest in physitestosteronemia group （0.26±0.08）,which was significantly lower than that in sham operation group（P 0.01）.Conclusions Exogenous testosterone,only at physiological level,has beneficial effects on serum lipids,lipoproteins,apolipoproteins and atherosclerosis in castrated male rabbits.