刺梨黄酮抗氧化应激抑制模型大鼠TGF-β1、TGF-βRⅠ延缓肾间质纤维化的实验研究  

Experimental Study of Rosa oxburghii Flavones Oxidation Stress Inhibition Rats’ TGF-β1 and TGF-βRⅠDelaying Renal Interstitial Fibrosis

作　　者：詹继红[1] 刘铭洁 郭银雪[1] ZHAN Jihong;LIU Mingjie;GUO Yinxue(Nephrology Dept. in First Affiliated Hospital of Human University of Chinese Medicine, Guiyang 550001, GuiZhou ,China)

机构地区：[1]贵阳中医学院第一附属医院肾内科

出　　处：《中华中医药学刊》2018年第6期1291-1293,I0001-I0004,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81460728)

摘　　要：目的：采用单侧输尿管结扎（UUO）方法建立肾间质纤维化模型大鼠,观察刺梨黄酮对UUO模型大鼠肾组织中氧化应激指标及TGF-β1、TGF-βRⅠ的影响。方法：将60只SD雄性大鼠适应性喂养1周后,随机分为假手术组（生理盐水）、模型组（生理盐水）、刺梨大剂量组（刺梨冻干粉）、刺梨中剂量组（刺梨冻干粉）、氯沙坦钾组（氯沙坦钾）各12只;除假手术组外,各组均行单侧输尿管结扎术（UUO）,假手术组只行输尿管分离,但不结扎。各组于分组当天,均以相对应的药物灌胃,疗程14 d。应用比色法、免疫组织化法,Western blotting等检测技术,观察大鼠肾组织丙二醛（MDA）和超氧化物歧化酶（SOD）含量以及肾组织TGF-β1、TGF-βRⅠ的表达。结果：与假手术组比较,模型组病理损伤程度显著增加,MDA含量增加、SOD含量降低（P〈0.01）,TGF-β1、TGF-βRⅠ的表达水平明显增加（P〈0.05）。与模型组比较各治疗组病理损伤减轻,MDA含量降低、SOD含量升高,TGF-β1、TGF-βRⅠ表达减少（P〈0.05）,跟剂量无关,中剂量组治疗疗效优于大剂量组（P〈0.05）。中剂量组与氯沙坦钾组比较差异无显著性（P〉0.05）。结论：刺梨黄酮与氯沙坦均能抑制单侧输尿管结扎肾间质纤维化大鼠的肾组织脂质过氧化物的产生,同时能增加抗氧化酶的含量,保护受损肾小管上皮细胞,有效改善肾脏纤维化病变,其机理可能与抗氧化应激、下调TGF-β1、TGF-βRⅠ的表达有关。Objective： By using unilateral ureteral obstruction （UUO） method to build renal interstitial fibrosis rat model and observe the effects of Rosa oxburghii flavones oxidative stress rats＇ TGF - β1 and TGF - βR I in renal tissue. Methods： After adaptive feeding 60 male SD rats for one week, we randomly divided model rats into sham - operation group （ saline）, model group （ saline）, high dosage of Rosa oxburghii group （ freeze - dried powder of Rosa oxburghii）, medium dosage of Rosa oxburghii group （ freeze - dried powder of Rosa oxburghii） and Losartan treatment group （ Losar- tan）, 12 in each group. Most of the groups were used UUO, except the sham -operation group which only proceed ure- teral separation, but no ligation. After grouping, each group were given the corresponding doses of the drug garage. Rats were sacrificed after 14 days of treatment, we investigated the renal pathological changes. The content of MDA and activi- ty of SOD in renal cortex were assessed by chemical colorimetry. Immunohistochemistry and Western blot were performed to examine the expressions of TGF - β1 and TGF - R I in the kidney. Results ： In comparison with the shame group, the renal pathological of model group changed significantly. The content of MDA was increased, whereas activity of SOD was decreased significantly（ P 〈 0. 01 ） and the expressions of TGF - β1 and TGF - 13R I were increased significantly in the kidney （P 〈 0.05）. The high dose group was more effective than the medium dose group（P 〈 0. 05）. The medium dose group and losartan potassium had no significant difference （ P 〉 0. 05 ）. Conclusion： Rosa oxburghii flavones may protect tubular epithelial cells to alleviate renal fibrosis in rats with UUO by reducing lipid peroxidation production and improving antioxidative enzyme contents as well as losartan potassium. Its mechanism may be antioxidant stress and related to reduc- ing the expressions of TGF - β1 and TGF - βR I.

关 键 词：刺梨黄酮 UUO 肾纤维化 氧化应激 转化生长因子-Β1 受体 

分 类 号：R285.5[医药卫生—中药学]