雷帕霉素对双侧输尿管梗阻再通大鼠肾脏的保护作用

Protective Effect of Rapamycin on Rat Kidney after Bilateral Ureteral Obstruction

目的探讨雷帕霉素对双侧输尿管梗阻再通(BUOR)大鼠肾脏肾小管的保护作用以及抗纤维化作用。方法 48只SD雄性大鼠随机均分为假手术组、BUO组和雷帕霉素组,每组各16只。BUO组和雷帕霉素组大鼠结扎双侧输尿管制作BUO模型,假手术组仅游离双侧输尿管。BUO组及雷帕霉素组输尿管梗阻24h后解除梗阻。雷帕霉素组于术前1天至处死当天每天予以雷帕霉素口服液[2mg/(kg.d)]灌胃。假手术组及BUO组用等体积生理盐水灌胃。3组大鼠于术后4、7天收集24h尿液及抽取静脉血检验,采用免疫组化及Western blot检测肾损伤分子-1(KIM-1)、白介素-18(IL-18)、转化生长因子-β1(TGF-β1)及α-平滑肌肌动蛋白(α-SMA)在肾脏的表达。结果雷帕霉素组大鼠第4、7天血肌酐及尿素氮均低于BUO组(P<0.05),肾脏KIM-1、IL-18、TGF-β1、α-SMA表达明显低于同时间点BUO组,但仍高于假手术组(P<0.05)。结论 雷帕霉素可能通过下调TGF-β1、α-SMA、KIM-1和IL-18的表达减轻BUO术后所致的肾间质纤维化,保护肾小管。

To explore the protective effects of rapamycin on bilateral ureteral obstruction recanalization rats. Methods Forty -eight rats were randomly individed into sham operation group （sham group） , BUO group, rapamycin treatment group. The bilater- al ureter were exposed and occluded in BUO group and rapamycin treatment group. Twenty -four hours later, the obstructed ureters were decompressed by removal of the ligature. Sham animals underwent identical surgical procedures, but the ureter was simply manipulated, the wound was then closed inlayers. Rapamycin was given 0.4ml per day[2mg/（ kg ~ d） ] by intragastric from the day before surgery until the rats were killed in rapamycin treatment group. Sham group and BUO group were given the same volume of saline by intragastric. The urine and blood were collected at 4days, 7days after surgery, and the functional data were observed. The expression of KIM - 1 ,IL - 18, TGF - ~1 and ct - SMA were examined by immnohistochemistry and immunoblotting. Results After release of obstruction, the serum creatinine and urea nitrogen in BUO group were higher than those in rapamycin treatment group at day 4 and 7 （ P 〈 0.05 ）. In papamycin treatment group, the protein expression of KIM - 1 ,IL - 18,TGF - [31, and ct - SMA in renal were significantly lower than those in BUO group at day 4 and 7, but still higher than those in the sham operation group （P 〈 0.05）. Conclusion The down - regulation of KIM - 1 ;IL- 18;TGF- β1 ;and a- SMA expression by rapamycin may play a protective role to alleviate BUO -induced interstitial fibrosis of kidney and protect the renal tubular after BUO.