放射治疗对大鼠新月体性肾炎进程的影响  

Effects of radiotherapy upon progression of crescentic glomerulonephritis in rats

作　　者：刘殿阁[1] 陈涵枝[1] 丁弘[1] 周建东[1] 汪湜[1] 

机构地区：[1]东南大学附属中大医院肾内科,南京210009

出　　处：《中华医学杂志》2009年第29期2072-2076,共5页National Medical Journal of China

基　　金：教育部留学回国人员科研启动基金（教外司留[2005]383号）;东南大学科技基金（KJ2009387）

摘　　要：目的探讨放射治疗对大鼠新月体性肾炎进程的影响。方法雄性SD大鼠随机分成：（1）对照组（n=12）；（2）新月体性肾炎组（n=23），肾毒性血清（NTS）静脉注射；（3）放射治疗组（n=55），NTS注射后第6、13、20、27天双肾接受0．5Gy X射线单次局部照射。照射后不同时间点处死各组动物，分别以NTS7dRa1d、NTS14dRa1d、NTS21dRa1d、NTS28dRa1d来命名NTS注射后第6、13、20、27天接受肾脏局部照射的治疗组动物。结果与相同时间点新月体性肾炎组比较，放射治疗组中NTS7dRa1d、NTS14dRa1d大鼠血清肌酐水平、肾小球细胞增殖度、新月体比例和肾小球硬化率在照射后第8天明显降低（P〈0．05），第15、22天显著性降低（P〈0．01），肾小管间质病变亦明显减轻。免疫组化表明，与相同时间点新月体性肾炎组比较，NTS7dRa1d、NTS14dRa1d大鼠肾内增殖细胞核抗原（PCNA）阳性细胞及巨噬细胞标识ED-1阳性的巨噬细胞明显减少（P〈0．05），TUNEL阳性凋亡细胞显著增加（P〈0．05），半胱氨酸蛋白酶3（caspase 3）及半胱氨酸蛋白酶7（caspase 7）肾内表达亦明显增强。连续切片提示：ED-1阳性的巨噬细胞同时具有TUNEL阳性表达。免疫印迹（Western blot）表明，放射治疗组caspase 3及caspase 7蛋白水平明显升高，并且p53基因蛋白水平亦显著性升高。结论放射治疗通过p53依赖性途径诱导细胞凋亡有效抑制大鼠新月体性肾炎进程。Objective To study the effects of radiaotherapy upon progression of crescentic glomerulonephritis in rats. Methods Male SD rats were divided into three groups ： （ 1 ） control （ n = 12 ）, sham-operation; （2） crescentic glomerulonephritis （n = 23 ）, intravenously inject with nephrotoxie serum （NTS）; （3）radiotherapy （n = 55） , a single low-dose irradiation of 0. 5 Gy X-ray to both kidneys at Days 6, 13, 20 and 27 after NTS injection, and sacnificed at different time points among control and crescentic glomerulonephritis rats. Radiotherapy rats have received local kidney irradiation at Days 6, 13, 20 and 27 after bolus NTS injection and would be referreds to as NTS7dRa1d, NTS14dRa1d, NTS21dRa1d and NTS28dRa1d, respectively. Results For NTS7dRa1d and NTSI4dRa1d rats of radiotherapy, the levels of serum creatinine, glomerular hypereellularity, crescents and global sclerosis were significantly lower at Days 8 （P 〈 0. 05 ）, 15, and 22 post-irradiation as compared with group of eresscentic glomerulonephritis of similar time intervals （P 〈 0. 01 ）. The extent of tubulointerstitial damage was also reduced, and radiotherapy associated histological improvements were accompanied by reduced macrophage infiltration in glomeruli and interstitium. The numbers of PCNA- and EDl-positive cells were reduced in the kidneys at Day 1 post- irradiation in NTS7dRal d and NTSI4dRa1d rats as compared with group of crescentic glomerulonephritis at similar time intervals （ P 〈 0. 05 ）. A larger number of TUNEL-positive cells were noted at Day 1 post- irradiation in rats irradiated at Days 6 ＆ 13 after NTS injection as compared with group of crescentic glomerulonephritis at similar time intervals （ P 〈 0. 05）. With regards to immunostaining for macrophages ED1 and TUNEL, serial sections of irradiated nephritic kidne showed that fewer EDl-positive macrophages were stained for TUNEL. As evaluated expression of active easpases 3 ＆ 7 was noted in irradiated kidneys as compared with the corre

关 键 词：放射治疗 新月体性肾炎 细胞凋亡 半胱氨酸蛋白酶 P53基因 

分 类 号：R686[医药卫生—骨科学]