前列腺素E1对糖尿病肾病大鼠肾脏细胞凋亡的影响

Effects of prostaglandin E1 on renal cell apoptosis in rats with diabetic nephropathy

目的观察前列腺素E1（PGE1）对糖尿病肾病（DN）大鼠肾脏细胞凋亡的影响。方法雄性Wistar大鼠65只，单次腹腔注射链脲佐菌素（STZ）制备DN大鼠模型。将造模成功的46只大鼠随机分为4组，PGEl组12只：前列地尔注射液（凯时）10／ug／d，静脉推注，10d；血管紧张素转换酶抑制剂（ACEI）组12只：盐酸贝那普利片（洛汀新）10mg／d，灌胃，8w；联合用药组11只：给予PGEl和ACEI联合治疗，剂量及时间同上；肾病对照组11只：仅给予相同体积生理盐水；另设正常对照组10只，处理同肾病对照组。治疗8w后处死所有动物并测定24h尿微量白蛋白、血尿素和血肌酐；HE染色观察肾脏病理和原位末端转移酶标记法（TUNEL）法检测细胞凋亡。结果治疗后8w，ACEI组、PGEl组、联合用药组24h尿自蛋白水平均低于肾病对照组[（374．6±54．1）ug，（570．0±72．5）gg，（253．1土28．9）“g比（1123．4±106．2）／xg，P〈0．01或P〈0．053；血尿素[（9．3±2．6）mmol／L，（11．0±3．5）mmol／L，（8．4±2．2）mmol／L比（15．1±4．0）mmol／L]和血肌酐[（74．5±19．2）umol／L，（83．5士15．8）“mol／L，（64．6±17．3）umol／L比（117．7±33．0）umol／L3水平均低于肾病对照组（P〈0．01或P〈0．05）；与肾病对照组比较，各用药组肾脏组织病理改变减轻，联合用药组病理形态最佳。细胞凋亡在肾小球区域不明显，各组间差异无统计学意义（P〉0．05）；除正常对照组外，各组肾小管细胞凋亡数显著多于‘肾小球。结论PGE1减少尿自蛋白的机制与肾小球细胞凋亡无明显相关，可能与。肾小管细胞凋亡有关。

Objective To investigate the effects of prostaglandin E1 （PGE1） on renal cell apoptosis in rats with diabetic nephropathy（DN）. Methods Totally 55 male Wistar rats were intraperitoneally injected with streptozotocin （STZ） to develop DN model. 46 successfully established DN rat models were randomly divided into 4 groups： PGE1 group received PGE1 intravenously at dose of 10 /ug · kg-1· d-1 for 10 d （n= 12）, angiotensin converting enzyme inhibitors（ACEI） group given ACEI orally at dose of 10 mg kg-1 d -1 for 8 W（n=12）, PGEI＋ ACEI group given both PGE1 and ACEI （n=11）, DN control group（n： 11） and normal control group（n= 10） given saline only. All rats were killed after 8 weeks and blood samples or kidney tissue were collected. Blood urea nitrogen （BUN）, serum ereatine（Scr）, albuminuria of 24 h were detected. Renal pathological morphology and apoptosis of renal ceils were observed by HE staining and terminal deoxynucleotidyl transferase- mediated dUTP nick end-labeling （TUNEL） test. Results At 8 week after treatment, the 24-hour urinary albumin levels were decreased significantly in the following order： DN control group〉 PGE1 group 〉 ACEI group 〉PGEI＋ ACEI group〉 control group[（374.6±54.1）ug, （570.0±72.5）ug, （253.1±28.9）/ug vs. （1123.4±106.2）ug, P〈0.01 or P〈0.053. BUN[（9.34±2.6）mmol/L, （11.0±3.5）mmol/L, （8.4±2.2）mmol/Lvs. （15.1±4.0）mmol/L]and Ser [（74. 5±19. 2） umol/L,（83.5±15.8）umol/L, （64.6±17.3） umol/L vs. （117.7±33.0）/Lmol/L]levels after treatment were also reduced in PGE1, ACEI and PGE1 ＋ ACEI groups as compared with DN control group （P〈0.01 or P% 0.05）. Pathological manifestations of all treatment groups showed better results than DN group, and PGE1＋ ACEI group was the best. There was no obvious apoptosis in glomerular area with on significant differences between groups. While apoptosis of renal tubules was observed in DN rats. Conclusions Renal tubule but not glomerular cell apoptosis may play some role in Prostaglandin E1 reducing albuminuria.