CAJ | 학술논문

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.
목적 탐토방사치료대대서신월체성신염진정적영향.방법 웅성SD대서수궤분성:(1)대조조(n=12);(2)신월체성신염조(n=23),신독성혈청(NTS)정맥주사;(3)방사치료조(n=55),NTS주사후제6、13、20、27천쌍신접수0.5Gy X사선단차국부조사.조사후불동시간점처사각조동물,분별이NTS7dRa1d、NTS14dRa1d、NTS21dRa1d、NTS28dRa1d래명명NTS주사후제6、13、20、27천접수신장국부조사적치료조동물.결과 여상동시간점신월체성신염조비교,방사치료조중NTS7dRa1d、NTS14dRa1d대서혈청기항수평、신소구세포증식도、신월체비례화신소구경화솔재조사후제8천명현강저(P<0.05),제15、22천현저성강저(P<0.01),신소관간질병변역명현감경.면역조화표명,여상동시간점신월체성신염조비교,NTS7dRa1d、NTS14dRa1d대서신내증식세포핵항원(PCNA)양성세포급거서세포표식ED-1양성적거서세포명현감소(P<0.05),TUNEL양성조망세포현저증가(P<0.05),반광안산단백매3(caspase 3)급반광안산단백매7(caspase 7)신내표체역명현증강.련속절편제시:ED-1양성적거서세포동시구유TUNEL양성표체.면역인적(Western blot)표명,방사치료조caspase 3급caspase 7단백수평명현승고,병차p53기인단백수평역현저성승고.결론 방사치료통과p53의뢰성도경유도세포조망유효억제대서신월체성신염진정.
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 nephrotoxic 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 NTS14dRa1d rats of radiotherapy, the levels of serum creatinine, glomerular hypercellularity, crescents and global sclerosis were significantly lower at Days 8 (P<0.05), 15, and 22 post-irradiation as compared with group of cresscentic 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 ED1-positive cells were reduced in the kidneys at Day 1 post-irradiation in NTS7dRa1d and NTS14dRa1d 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 EDi and TUNEL, serial sections of irradiated nephritic kidne showed that fewer ED1-positive macrophages were stained for TUNEL. As evaluated expression of active caspases 3 & 7 was noted in irradiated kidneys as compared with the corresponding group of crescentic glomerulonehritis at similar time intervals. Western blot analysis showed marked increase in the expression of active caspase 3 & 7 in irradiated kidneys as compared with NTS injection only the expressiou of A marked increase in the expression of p53 protein, closely related to radiation-induced apoptosis, was also observed in irradiated kidneys as compared with NTS injection only. Conclusion Radiotherapy inhibits the progression of experimental crescentic glomerulonephritis through inducing apoptosis by a p53-dependent pathway.