辛伐他汀对糖尿病大鼠肾脏细胞凋亡的影响研究

Effect of Simvastatin on the apoptosis of renal cells in diabetic rats

目的观察辛伐他汀对糖尿病大鼠肾脏氧化应激和凋亡蛋白表达的影响,并探讨其可能的抗凋亡分子机制。方法 24只SD大鼠随机分为正常对照组(NC,n=8)、糖尿病组(DM,n=8)和辛伐他汀治疗组(DM+Sim,n=8)。腹腔注射STZ建立糖尿病大鼠模型。每天记录1次体重,每3d测1次血糖,在辛伐他汀治疗第1周末和第4周末分别检测24h尿蛋白含量。实验结束后,抽取腹主动脉血,检测TC和TG,并取出双侧肾脏,检测肾脏组织丙二醛(MDA)、过氧化物歧化酶(SOD)水平及蛋白nephrin、p53、p-p53、Bax和Bcl-2的表达。结果与NC组比较,DM组和DM+Sim组体重增长缓慢,而血糖迅速升高;DM组和DM+Sim组体重和血糖比较,差异无统计学意义。辛伐他汀治疗第1周末时,与NC组比较,DM组24h尿蛋白增加(P<0.01);辛伐他汀治疗第4周末时,DM组和DM+Sim组24h尿蛋白均增加,与NC组比较,DM组24h尿蛋白增加,而DM+Sim组较DM组24h尿蛋白下降(P<0.05)。与NC组比较,DM组TC、TG和MDA水平及p53、p-p53和Bax表达升高(P<0.01),而SOD活性以及nephrin、Bcl-2表达降低(P<0.01);与DM组比较,DM+Sim组TC、TG和MDA水平及p53、p-p53和Bax表达降低(P<0.05或P<0.01),而SOD活性及nephrin、Bcl-2表达升高(P<0.05)。结论辛伐他汀可通过抑制氧化应激,进而抑制促凋亡蛋白和上调抗凋亡蛋白的表达来保护糖尿病大鼠的肾脏。

Objective To evaluate the effect of Simvastatin on oxidative stress and apoptotic protein expression in kidney in diabetic rats and to explore the possible anti-apoptosis mechanism. Methods 24 SD rats were randomly divided into three groups： normal control group （NC, n = 8）, diabetic mellitus group （DM, n=8） and Simvastatin treatment group （DM＋Sim, n=8）. The diabetic rat model was established by injecting STZ intraperitoneally. During the experiment, the rats were weighted every day, and the blood glucose of the rats was measured every three days. The 24-hour urinary protein of rats was measured at the end of first and the fourth week of Simvastatin treatment. At the end of the experiment, the blood in abdominal aorta was drawn and the total cholesterol （TC） and triglyceride （TG） were measured. The level of malondialdehyde（MDA） and the activity of superoxide dismutase （SOD） as well as the expression of nephrin, p53, p-p53, Bax and Bcl-2 in kidney of rats were detected. Results The body weight increased slowly while the blood glucose increased rapidly in DM group and DM＋Sim group than in NC group. There was no difference in body weight and blood glucose between DM group and DM＋Sim group. At the end of first week of Simvastatin treatment, 24 h urinary protein increased significantly in DM group than in NC group （P〈0.01）. At the end of the fourth week of Simvastatin treatment, 24-hour urinary protein increased in DM group and DM ＋ Sire group, and was higher in DM group than in NC group. However, 24-hour urinary protein was lower in DM＋Sim group than in DM group （P〈0. 05）. The level of TC, TG, MDA and the expression of p53, p-p53 and Bax in kidneys were significantly higher, while the activity of SOD and the expression of nephrin and Bcl-2 were significantly lower in DM group than in NC group （P〈O. O1）. The level of TC, TG, MDA and the expression of p53, p-p53 and Bax were significantly lower （P〈0.01 or P〈0. 05）, while the activity of SOD and the expression of nephrin and Bcl-2 were significantly higher in DM group than in NC group （P〈0. 05）. Conclusion Simvastatin may protect the kidney of diabetic rats by inhibiting oxidative stress, the expression of pro-apoptotic proteins and up-regulating the anti-apoptotie proteins.