睾酮对自发性高血压大鼠肾脏结构和功能的影响

Effect of testosterone on kidney structure and function in spontaneously hypertensive rats

目的研究睾酮对自发性高血压大鼠(spontaneously hypertensive rats,SHR)肾脏结构和功能的影响。方法分别将18只10周龄的SHR及Wistar-Kyoto rats(WKY大鼠)进行卵巢切除,并随机分为卵巢切除(ovariectomized,OVX)组,卵巢切除后雌激素补充组(OVX+EB)和卵巢切除后雄激素补充组(OVX+TP),分别给予茶油0.5ml/(kg·2d)、苯甲酸雌二醇(estradiol benzoate,EB)0.25mg/(kg·2d)、丙酸睾酮(testosterone propionate,TP)3mg/(kg·2d)肌肉注射,持续8周。分别在实验初,第4和第8周末用尾部套囊法测定尾动脉收缩压(SBP)。在第8周末代谢笼收集大鼠24h尿液,ELISA法检测尿微量白蛋白(urinal microalbumin,MAU)和尿肌酐浓度,计算蛋白肌酐比值。麻醉处死大鼠,ELISA法检测血清睾酮、雌二醇及孕酮浓度。分离右肾,称量,切片、HE染色观察肾病理改变。结果各组与实验初SBP相比,SHR及WKY OVX组及OVX+TP组4周末和8周末SBP逐渐升高(P<0.05),OVX+EB组SBP改变不明显(P<0.05)。和对应的OVX组8周末SBP相比,SHR及WKY大鼠OVX+TP组SBP明显升高(P<0.05),OVX+EB组SBP明显降低(P<0.05)。和对应的OVX组大鼠相比,补充雄激素均能显著增加SHR及WKY肾脏质量(P<0.05)及肾指数(P<0.05)。同时OVX及OVX+TP组均出现不同程度肾小管损伤,OVX+TP大鼠肾小管损伤较OVX组更严重,尤其是SHR。分别与SHR+OVX组和WKY+OVX+TP组相比,SHR+OVX+TP组MAU浓度和尿蛋白肌酐比值均显著升高(P<0.01),而WKY+OVX+TP组仅MAU浓度升高(P<0.01),蛋白肌酐比值无明显改变(P>0.05)。结论生理剂量的睾酮可以加重卵巢切除SHR肾结构改变和功能损伤,血压升高是其可能的机制之一。

Objective To investigate the effect of testosterone on kidney structure and function in spontaneously hy- pertensive rats （SHR）. Methods Eighteen SHR and Wistar-Kyoto rats （WKY） of ten weeks old were ovariectomized and assigned to three groups randomly： ovariectomized （OVX） group, estrogen supplement after ovariectomy （OVX＋EB） group and androgen supplement after ovariectomy （OVX＋TP） group. They accepted intramuscular injection of tea oil 0. 5 ml/（ kg · 2 d）, estradiol benzoate （EB） 0. 25 mg/（ kg · 2 d） and testosterone propionate （ TP ） 3 mg/（ kg · 2 d） respec- tively for 8 weeks. The tail artery systolic blood pressure （SBP） was measured at the beginning, 4th and 8th week of the study respectively by tail cuff method. The rats were put into metabolic cages and the urine of 24 hours was collected, then the urinary albumin and urinary creatinine concentration were detected by ELISA, and the ratio of protein to creatinine was calculated. At last, all the rats were anesthetized and killed, blood and tissue samples collected, and then the concentra- tions of serum testosterone, estradiol and progesterone were detected by ELISA. The right kidney weight was measured and pathological changes were observed. Results Compared with SBP at the beginning of our study, SBP of OVX and OVX＋ TP of WKY or SHR increased continuously during 8 weeks experiment（P〈0. 05）. The changes in OVX＋EB group were not significant （P〉0.05）. Compared with SBP of corresponding OVX group at 8th week, SBP of OVX＋TP group of WKY or SHR was significantly increased, while SBP in OVX＋EB group was decreased（P〈0. 05）. Meanwhile, TP intervention in- creased the single kidney weight （P〈0.05） and the ratio of kidney to body weight （P〈0. 01 ） of both SHR or WKY. OVX and OVX＋TP group of SHR or WKY showed glomerular and renal tubular injury. What＇s more, the changes in OVX＋TP group were more serious than those in OVX group, especially for SHR. Urinary albumin concentration and the ratio of pro- tein to creatinine of OVX＋TP group of SHR was much higher than those in OVX group of SHR and OVX＋TP group of WKY （P〈0. 01 ）. While TP supplement only increased urinary albumin concentration in WKY significantly （P〈0. 01 ）. but hadno effect on the ratio of protein to creatinine （P〉 O. 05 ）. Conclusions Physiological dose of testosterone can aggravatethe changes of renal structure and function impairment of ovariectomized SHR and elevated blood pressure might be one of the possible mechanisms.