雷公藤多甙对糖尿病肾病大鼠肾脏肿瘤坏死因子-α、白细胞介素-4表达和尿微量白蛋白的影响  

Effect of tripterygium wilfordii polyglucosides on the expression of tumor necrosis factor-α and interleukin-4 in renal tissue from rats with diabetic nephropathy

作　　者：孔岩[1] 单春艳[1] 常宝成[1] 杨菊红[1] 郑妙艳[1] 任惠珠[1] 王颖[1] 郭航[1] 杨轶萍[1] 刘婕妤[1] 陈莉明[1] 

机构地区：[1]天津医科大学代谢病医院糖尿病肾病科卫生部激素与发育重点实验室,300070

出　　处：《中华糖尿病杂志》2013年第9期541-546,共6页CHINESE JOURNAL OF DIABETES MELLITUS

摘　　要：目的观察不同剂量雷公藤多甙（TWP）对于糖尿病肾病（DN）大鼠肾脏肿瘤坏死因子（TNF-α）、白细胞介素-4（IL-4）表达的影响，探讨其对尿微量白蛋白的疗效和抗炎作用。方法将5～6周龄体重（190±15）gSD雄性大鼠68只，采用随机数字表法分为正常对照组（NC组，n=8）和高糖高脂饲料组（n=60），4周后以链尿佐菌素（STZ）诱导2型糖尿病，进一步将高糖高脂饲料组分为模型对照组（DM组）、雷公藤多甙给药低剂量组（TL组，6mg·kg-1·d-1）、中剂量组（TM组，12mg·kg-1·d-1）、高剂量组（TH组，24mg·kg-1·d-1），每组15只，于第5周开始灌胃治疗，第8周末处死取材。观察大鼠高糖高脂饲料喂养后基础血糖、血脂，成模后第0、4、8周24h尿微量白蛋白（UMA）、第8周末肝肾功能，实时定量-聚合酶链反应（RT—PCR）检测肾脏中TNF-α、IL_4基因和蛋白的表达情况。各组间计量资料采用单因素方差分析以及独立样本x检验。结果（1）高糖高脂饲料组UMA自第4周起明显高于NC组（t=11．588、23．452、16．033、19．992，均P〈0．05）；（2）第8周末，DM组大鼠UMA、肾重／体重（KW／BW）明显高于NC组（t=17．276、10．477，均P〈0．05）；3个给药组UMA、KW／BW较DM组有不同程度下降（t=13．274、15．877、10．480、3．588、4．794、3．134，均P〈0．05），其中TM组降低最明显，TL、TH组次之；各组大鼠肝肾功能无差别（F=0．610、1．263、1．032、0．278，均P〉0．05）；（3）5组TNF-α、IL-4mRNA和蛋白表达差异存在统计学意义（F=87．415、15．623、152．196、11．377，均P〈0．05），与NC组相比，DM组大鼠肾脏中TNF-α mRNA和蛋白表达明显升高（t=19．961、8．888，均P〈0．05），IL-4表达无明显降低（P〉0．05）；与DM组相比，3个给药组TNF-αmRNA和蛋白表达有不同程度降低（t：5．233、8．397、4．021、4．765、5．977、2．Objective To investigate the anti-proteinuria and anti-inflammatory effect of the different dosages of tripterygium wilfordii polyglucosides （TWP） in rats with diabetic nephropathy. Methods A total of 68 male SD rats aged 5-6 weeks and weighed （ 190 ± 15 ） g were divided into the normal control group （ NC, n = 8 ） and the high glucose fatty diet group （ HGFD, n = 60） by the randomized table method. After feeding with high glucose fatty diet for 4 weeks, rats in the HGFD group were induced into the diabetics by Streptozotocin （STZ） and further divided into the diabetic model group （DM group ） , TWP low-dose group （TL group, 6 mg/kg） , TWP middle-dose group （TM group, 12 mg/kg） and TWP high-dose group （TH group, 24 mg/kg）, with 15 rats in each. At week 5, after the induction of DN in the HGFD group, the intervention was given by gavage and all rats were sacrificed at the end of the week 8. The following parameters were tested in all rats： blood glucose and blood lipid after HGFD, UMA at week 0, 4 and 8, liver and kidney function and the expression of tumor necrosis factor-c~, interleukin-4 in the renal tissue at the the end of week 8. Difference was compared by the single factor analysis and the independent-samples t test of variance. The multivariate analysis of covariance was applied to control the baseline difference between the groups and the effect of weight, triglycerides and total cholesterol on the expression of TNF-α and IL-4. Results （ 1 ） The levels of blood glucose （ t = 4. 404, 3. 393, 2. 699, 2. 940, all P 〈 0. 05）, TG and TC （ t = 13. 546,15.251, all P 〈 0. 05 ）in the HGFD group were significantly higher than those in the NC Group. The UMA levels were higher in the HGFD group than that in the NC group （t = 11. 588, 23. 452, 16. 033, 19. 992,all P 〈 0. 05）. （2） At the end of the week 8, the levels of UMA and Kidney Weight/Body Weight （KW/BW） were higher in the HGFD group than those in the NC group（t = 17. 276, 10. 477 ,all P 〈0.

关 键 词：糖尿病 2型 糖尿病肾病 雷公藤多甙 肿瘤坏死因子-Α 白细胞介素_4 

分 类 号：R285.5[医药卫生—中药学]