摘要
目的研究维生素D是否通过抑制氧化应激在糖尿病肾病(DN)中产生保护作用。方法应用链脲佐菌素(STZ)腹腔注射诱导糖尿病大鼠模型,经过两个月持续喂养诱导DN模型。将大鼠随机分为三组,糖尿病肾病骨化三醇干预组(DNR组)予骨化三醇0.2μg·kg^(-1)·d^(-1)灌胃,正常对照组(NC组)和DN组仅给予等容量花生油,均灌胃一个月。检测给药前后大鼠体重、随机血糖、血脂、血清丙二醛及总超氧化物歧化酶(T-SOD)、总抗氧化能力(T-AOC)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-PX)水平等。电镜观察大鼠肾脏超微结构改变,real-time PCR检测大鼠肾脏谷胱甘肽过氧化物酶1(GPX1)、超氧化物歧化酶1和2(SOD1、SOD2)mRNA表达水平。结果与NC组比较,DN组和DNR组大鼠体重降低,血糖、三酰甘油水平升高(P<0.05或P<0.01)。DN组肾重-体重比和尿微量白蛋白-肌酐比值(UA/Cr)明显高于NC组(P<0.01),DNR组肾重-体重比和UA/Cr均低于DN组(P<0.05或P<0.01)。DN组血清丙二醛水平高于NC组,T-SOD、T-AOC、CAT、GSH-PX活性及肾脏GPX1、SOD1、SOD2 mRNA水平均低于NC组(P<0.01),肾脏超微结构出现明显异常。DNR组血清丙二醛水平低于DN组,T-SOD、T-AOC、CAT、GSH-PX活性及肾脏GPX1、SOD1、SOD2 mRNA水平均高于DN组(P<0.05或P<0.01),肾脏超微结构异常明显改善。结论维生素D可能通过增加肾脏的抗氧化能力减轻DN大鼠的氧化应激,从而发挥其对DN的保护作用。
AIM To study whether vitamin D inhibits oxidative stress to protect diabetic nephropathy （DN）. METHODS The diabetic rats were induced by intraperitoneal injection with streptozotocin. Then, the diabetic rats were fed with rodent chow about 2 months to induce DN. The rats were randomly divided into three groups. The intragastric administration with calcitriol 0.2 p·g·kg-1·d-1 was applied to DN rats in the calcitrioltreatment （DNR）group. The rats in the normal control （NC） group and DN group were only treated with equivalent arachisoil. After 1 month treatment, the body weight of rats, random blood glucose, the level of malondialdehyde （MDA）, total superoxide dismutase （T- SOD）, total antioxidant capacity （T- AOC）, hydrogen peroxidase （CAT） and glutathion peroxidase （GSH-PX） of rats serum in each group were tested. The ultra-structure of rats kidneys was observed with electron microscope. The mRNA expression of glutathion peroxidase 1 （GPX1）, superoxide dismutase 1 and 2 （SOD1, SOD2） of kidneys were detected by means of real-time PCR. RESULTS Compared with NC group, the body weight of rats was decreased in the group DN and DNR, but serum glucose and triglyceride were increased significantly （P 〈 0.05 or P 〈 0.01 ）. The kidney weight to body weight ratio and UA/Cr in the group DN were more elevated than those of group NC and DNR （P 〈 0.05 or P 〈 0.01）. Compared with group NC, the serum MDA in the group DN was higher and the activity of serum T-SOD, T-AOC, CAT, GSH-PX and the renal mRNA expression of GPX1, SOD2 and SOD1 were reduced （P 〈 0.01 ）. In the meantime, the ultra-structure of rats kidneys showed obviously abnormal changes in the group DN. Compared with group DN, the MDA in the group DNR was reduced obviously, while the activity of serum T-SOD, T-AOC, CAT, GSH-PX and the renal mRNA expression of GPX1, SOD2 and SOD1 in group DNR were increased （P 〈 0.05 or P 〈 0.01）. As a result, the renal ultra-structure improved predominantly. CONCLUSION Vitamin D can improve DN of rats significantly. This protective effect might be related to alleviate oxidative stress of rats by raising anti-oxidant ability of kidney.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2013年第9期721-726,共6页
Chinese Journal of New Drugs and Clinical Remedies
基金
常州市社科基金项目(CS20092021)
