【摘要】 目的:探讨PI3K/Akt信号通路在过度训练致急性肾损伤中的变化和作用,以及山莨菪碱是否通过PI3K/Akt信号通路起到肾脏保护作用。方法:将60只大鼠随机分为四组:正常对照组(NC)、过度训练组(OT)、过度训练+山莨菪碱组(OTA)、过度训练+渥曼青霉素组(OTW)。除NC组外,其余各组分为建模后即刻、6 h和24 h三个亚组。通过一次性游泳力竭运动建立过度训练模型。OTW和OTA组于建模前20分钟分别腹腔注射渥曼青霉素25μl/kg和山莨菪碱10 mg/kg。于相应时点检测血肌酐、尿素、肌酸激酶水平;Western blot法检测肾组织Akt、p-Akt、Nrf2表达;TUNEL法检测肾脏细胞凋亡。结果:与NC组相比,OT组出现肾功能损伤和细胞凋亡,p-Akt、Nrf2表达上调(P<0.05)。与OT组相比,OTA组部分时点肾功能改善,细胞凋亡减少,p-Akt、Nrf2表达进一步上调(P<0.05)。OTW组总体表现与OTA组相反(P<0.05)。各组间Akt表达无明显差异。结论:在过度训练致急性肾损伤中,PI3K/Akt通路激活增多,进而减少过氧化反应,改善肾功能,抑制细胞凋亡。山莨菪碱可通过该通路发挥肾脏保护作用。更多还原

【Abstract】 Objective: To investigate the the effect and mechanism of PI3K/Akt signaling pathway in over-training induced acute kidney injury,and whether anisodamine protects the injured kidney via PI3K/Akt signaling pathway. Methods: 60 Wistar rats were randomly divided into four groups: normal control group(NC),over-training group(OT),over-training and anisodamine group(OTA),over-training and wortmannin group(OTW). Over-training models were created by one-time exhaustive swimming. OTA and OTW group were respectively given wortmannin 25 μl/kg and anisodamine 10 mg/kg by intraperitoneal injection. Serum creatinine(Cr),urea nitrogen(BUN) and creatine kinase were measured with autobiochemical analyzer. The expressions of Akt,p-Akt and Nrf2 were examined by western blot. The percentage of apoptosis cells was detected by TUNEL. Results: Compared with the NC group,parts of the Cr,BUN,CK,the percentage of apoptosis cells and the p-Akt and Nrf2 expressions of OT group increased significantly(P <0. 05). Compared with the OT group,parts of the Cr,BUN,CK,the percentage of apoptosis cells of OTA group increased further(P <0. 05). Parts of the p-Akt and Nrf2 expressions of OTA group were significantly higher than OT group(P <0. 05). The manifestations of OTW group were generally contrary to OTA group(P < 0. 05). There was no significant difference of Akt expressions among each group. Conclusion: In over-training induced acute kidney injury,PI3K/Akt signaling pathway could be activated increasingly and then inhibit peroxidation and alleviate renal injury. Anisodamine plays a protective role by activating this signaling pathway.更多还原