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作 者:刘奇[1] 陈姝君[1] 刘凤华 王晓菁[1] 史振伟 陈海平[1]
机构地区:[1]首都医科大学附属北京友谊医院医疗保健中心老年肾病科,北京100050 [2]煤炭总医院肾内科,北京100028
出 处:《临床和实验医学杂志》2014年第23期1925-1929,共5页Journal of Clinical and Experimental Medicine
摘 要:目的探讨雷公藤甲素对肾小球内核因子-κB(NF-κB)、诱导型一氧化氮合酶(i NOS)、内皮型一氧化氮合酶(e NOS)及血管内皮生长因子(VEGF)表达的影响及其对糖尿病大鼠肾小球内皮细胞的保护作用。方法采用链脲佐菌素制作大鼠糖尿病模型,正常对照组、糖尿病对照组及雷公藤甲素治疗组各16只,各组分别于4周、8周处死半数大鼠,测定血糖、血肌酐(SCr)、血尿素氮(BUN)、尿白蛋白(UAE);透射电镜观察肾小球内皮细胞的变化;免疫组化技术检测肾组织中NF-κB、i NOS、e NOS和VEGF,并用Image-pro plus 6.0病理图像分析软件进行半定量分析;实时定量PCR(RT-PCR.)法检测肾组织i NOS、e NOS和VEGF的mRNA表达。结果 1糖尿病组SCr、BUN、UAE较正常组升高,8周时更为明显;与糖尿病组比较,4周时雷公藤甲素治疗组上述指标变化不明显,8周时有明显下降;2糖尿病组肾小球NF-κB、i NOS、e NOS、VEGF表达水平较正常组增加,8周时明显;4周、8周时雷公藤甲素治疗组上述指标均较糖尿病组明显下降;38周时肾小球内NF-κB与i NOS、VEGF与e NOS、NF-κB与VEGF的表达呈正性相关;4透射电镜观察下,三组肾小球内皮细胞结构无明显差异。结论雷公藤甲素可能通过抑制肾小球组织内NF-κB、i NOS、e NOS及VEGF的表达,发挥对糖尿病大鼠肾小球内皮细胞的间接保护作用。Objective To explore the effects of triptolide( TP)on expressions of NF-ΚB,NOS and VEGF in glomeruli and the effect of protection on glomerular endotheliocyte in diabetic rats. Methods Diabetes was induced in rats by intraperitoneal injection of STZ. The rats were divided into three groups:normal control group(n=16),triptolide treated diabetic rats group(n=16)and untreated diabetic rats group(n=16 ). Eight rats in each group were executed at the end of 4 weeks and 8 weeks respectively. After execution,PG,SCr,BUN and UAE of the rats were measured;changes of glomerular capillary endotheliocytes were observed through transmission electron microscope;NF-κB,iNOS,VEGF and eNOS proteins in renal tissue were detected by immunohistochemistry and semiquantitative analysis was made by Image-pro plus 6. 0 software;the expressions of iNOS mRNA,VEGF mRNA and eNOS mRNA were obtained by RT-PCR. Results The levels of SCr,BUN and UAE were higher in diabetic group than normal control group,but they were lower in triptolide treated group than untreated diabetes group. The expressions of NF-κB,iNOS,eNOS and VEGF in the glomeruli of untreated diabetes group were increased in comparison with the control group,but they were decreased in triptolide treated group than untreated diabetes group. There were positive correlations between the expressions of NF-κB and iNOS,NF-κB and VEGF,and VEGF and eNOS. There was no obvious difference in the structure of glomerular capillary endotheliocytes among three groups. Conclusion Triptolide may protect glomerular endotheliocyte of diabetic rats by inhibiting the expressions of NF-κB,iNOS, eNOS and VEGF in glomeruli.
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