雷公藤多苷对糖尿病肾病大鼠的抗氧化应激作用

Antioxidative effect of Tripterygium wilfordii polyglycosides on diabetic rats

目的观察雷公藤多苷(TWP)对糖尿病性肾病大鼠的抗氧化应激作用。方法大鼠ip给予链脲佐菌素(STZ)制备DN模型。3周后造模成功,ig给予TWP 4.5,9.0和18.0 mg·kg-1,每天1次,连续8周。实验过程中观察大鼠的体质量、毛发和精神状况等。实验结束前2 d将大鼠置代谢笼,收集24 h尿液,用于检测24 h尿白蛋白排泄率(24 h UAER)。用药8周末,自动生化分析仪检测血肌酐(Scr)、尿素氮(BUN)和尿肌酐(Ucr)水平,并计算肌酐清除率(Clcr);可见光方法检测血清过氧化氢酶(CAT)活性,比色法测定血清超氧阴离子(O÷2)水平。比色法测定肾组织谷胱甘肽过氧化物酶(GSH-Px)活性,硫代巴比妥酸缩合法检测丙二醛(MDA)含量;HE染色观察肾组织病理改变。结果与正常对照组相比,模型对照组大鼠逐渐出现多饮、多尿、多食、消瘦以及反应迟钝、毛发枯黄、尾巴苍白湿冷、精神萎靡等现象;空腹血糖、BUN和24 h UAER均显著增高(P<0.01),Clcr明显降低(P<0.01);血清CAT活性和肾组织中GSH-Px活性明显降低(P<0.01),血清O÷2水平和肾组织MDA含量明显升高(P<0.01);肾小球肥大,系膜细胞增生,肾小球变形。与模型对照组比较,ig给予TWP 9和18 mg·kg-1可改善大鼠一般状况,BUN和24 h UAER明显降低(P<0.01),Clcr和血清CAT显著升高(P<0.01),O÷2和MDA含量降低(P<0.01),GSH-Px明显升高(P<0.01),肾组织病理变化明显减轻。TWP 4.5 mg·kg-1对上述指标均无明显影响。结论 TWP能明显改善糖尿病性肾病大鼠的肾功能,其机制可能与抑制氧化应激和增强机体抗氧化能力相关。

OBJECTIVE To investigate the possible protective effect of Tripterygium wilfordii polyglycoside（ TWP） on experimental diabetic nephropathy（ DN） rats and its possible mechanism. METHODS The diabetic model was induced by a single intraperitoneal injection of streptozotocin（ STZ） 65 mg· kg^-1. Three weeks after modeling,TWP 4. 5,9. 0 and 18. 0 mg·kg^-1was ig given to rats,once daily, for 8 consecutive weeks. During the experiment,the changes of body mass,hair,mental health of rats were observed. Two days before the end of the experiment,the rats were placed into metabolic cages to collect 24 h urine in order to detect 24 h urinary albumin excretion rate（ UAER）. The rats were given TWP for 8 weeks and anesthetized with 10% chloral hydrate. The blood was collected from the heart and centrifuged,serum creatinine and urine creatinine were measured,and creatinine clearance（ Clcr） was calculated. Blood urea nitrogen（ BUN） and the serum catalase（ CAT） activity were tested by optical method while the level of serum superoxide oxygen anion（ O2^÷） was tested by colorimetry. The level of malondialdehyde（ MDA） was determined by thiobarbituric acid condensation,and glutathione peroxidase（ GSH-Px） activity was tested by colorimetry. The right kidney was HE stained to observe pathological changes. RESULTS Compared with normal control group,the rats in model control group developed polydipsia,polyuria,polyphagia,body mass loss,unresponsiveness,brown hair,pale tail and apathy clammy. Besides,blood glucose,BUN and 24 h UAER were significantly higher（ P〈0. 01）,but Clcr was lower（ P〈0. 01）. The activity of serum CAT and GSH-Px in renal tissue was significantly lower（ P〈0. 01）,while the level of serum O2^÷ and MDA in the renal tissue was significantly higher（ P〈0. 01）. Compared with model control group,TWP 9. 0 and 18. 0 mg·kg^-1could improve the general condition of rats. BUN and 24 h UAER were obviously reduced（ P〈0. 01）,Clcrand serum CAT were increased obviously（ P〈0. 01）,the level of MDA and O2^÷ were reduced obviously（ P〈0. 01）,and GSH-Px level was increased（ P〈0. 01）. TWP 9. 0 and 18. 0 mg·kg^-1could significantly improve the renal histopathological changes of rats. TWP 4. 5 mg·kg^-1 had no significant effect on the above indicators. CONCLUSION TWP has protective effect on the renal function of experimental DN rats. The mechanism may be related to inhibition of the oxidative stress and enhancement of the body antioxidant capacity.