叉头转录因子O1在冬虫夏草预防糖尿病模型大鼠对比剂肾病中的机制  

Mechanism of FoxO1 in cordyceps preventing diabetic contrast-induced nephropathy rats

作　　者：戈立秀 赵凯[2] 高巧营[3] 宗春辉[3] 常艳敏[1] GE Li-Xiu;ZHAO Kai;GAO Qiao-Ying(Clinical Laboratory, Tianjin Nankai Hospital, Tianjin 300100, China)

机构地区：[1]天津市南开医院检验科,天津300100 [2]天津市南开医院心内一科,天津300100 [3]天津市中西医结合急腹症研究所

出　　处：《中国老年学杂志》2019年第20期5050-5055,共6页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(81503409)

摘　　要：目的 探讨叉头转录因子(Fox)O1在冬虫夏草预防糖尿病模型大鼠对比剂肾病中的机制。方法 SD大鼠80只,随机选取20只为正常对照组(N组),其余60只腹腔注射链脲佐菌素(60mg/kg)建立糖尿病模型,造模成功后再随机分为对比剂肾病组(M组)、冬虫夏草组(D组)、普罗布考组(P组)。10w后,N组和M组给予生理盐水灌胃,D组和P组分别给予冬虫夏草(3.0g/kg)和普罗布考(500mg/kg)灌胃。7d后,麻醉状态下,除N组外,其他三组给予碘克沙醇320(2.0g/kg)。取血标本测血清肌酐(Scr)、尿素氮(BUN),取尿标本测尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤因子(KIM)-1、白细胞介素(IL)-18;肾脏标本用于肾脏病理研究、氧化应激指标检测、蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)/P70核糖体蛋白S6激酶(P70S6K)通路及FoxO1的研究。结果 与M组比较,D组Scr、BUN、NAGL、KIM-1、IL-18水平均明显降低(P<0.05),P组BUN、Scr、NAGL、IL-18含量明显降低(P<0.05),而KIM-1无明显变化(P>0.05)。与M组比较,D组丙二醛(MDA)含量明显降低,而一氧化氮(NO)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)和总抗氧化能力(T-AOC)含量明显升高;P组MDA含量亦明显降低,NO、NOS和SOD含量明显升高(P<0.05),T-AOC无明显变化。与M组比较,D组和P组磷酸化(p-Akt)、p-mTOR、p-P70S6KmRNA及蛋白表达水平均明显升高,p-FoxO1mRNA水平和蛋白表达明显降低,p-FoxO1/FoxO1比值显著降低。结论 冬虫夏草可通过上调信号通路Akt/mTOR/P70S6K蛋白表达水平,进而促使FoxO1高表达,减少其磷酸化水平,减轻氧化应激和肾细胞凋亡,对糖尿病对比剂肾病大鼠的肾脏具有较好的保护作用。Objective To investigate the mechanism of FoxO1 in the cordyceps preventing diabetic contrast-induced nephropathy (CIN) rats. Methods Twenty rats were randomly selected as the normal control group (N group), and the sixty rats intraperitoneal injected of streptozotocin were selected to establish diabetic model, and then were randomly divided into the model of CIN group (M group), cordyceps group (D group) and probucol group (P group). After 10 weeks, the rats in the D group, P group were fed with Cordyceps (3.0 g/kg), probucol (500 mg/kg) by gavage, N group and M group were fed with physiological saline. After 7 days, in anesthetic state, except for N group, the other three groups were given ioditan 320 (2.0 g/kg). Blood samples were taken to measure BUN, Scr level.Urine were taken to measure NGAL, KIM-1, IL-18 level. The left kidney was used for pathological research, the right kidney was used for the related indicators of oxidative stress, the RT-PCR and Western blot examination of Akt/mTOR/P70S6K with FoxO1. Results Compared with those of M group, the levels of BUN, Scr, NGAL, KIM-1 and IL-18 were all obviously decreased in D group ( P <0.05), BUN, Scr, NGAL, IL-18 were all significantly decreased ( P <0.05), but there was no significance in KIM-1 in P group ( P >0.05). Compared with those of M group, MDA was decreased, NO, NOS, SOD and T-AOC were increased significantly in D group, MDA was obviously decreased, NO, NOS and SOD were significantly increased, and there was no significance in MDA in P group. Compared with those of the M group, the levels of Akt/mTOR/P70S6K mRNA and protein expression in D group and P group were all significantly increased, the levels of mRNA and protein expression about FoxO1 were also significantly increased, but the expressions of p-FoxO1 significantly and p-FoxO1/FoxO1 was significantly decreased. Conclusions Cordyceps could increase the level of Akt/mTOR/P70S6K mRNA and protein expression, and then promote the high expression of FoxO1, reduce the level of phosphorylation of Fo

关 键 词：叉头转录因子O1 冬虫夏草 糖尿病 对比剂肾病 

分 类 号：R541.4[医药卫生—心血管疾病]