CAJ | 학술논문

目的观察 mTOR 抑制剂（雷帕霉素）联合血管紧张素Ⅱ受体阻滞剂（坎地沙坦）对糖尿病肾病的作用。方法24只2型糖尿病模型 db/ db 小鼠随机均等分为糖尿病组（D组）、雷帕霉素治疗组（R 组）、坎地沙坦治疗组（C 组）、雷帕霉素+坎地沙坦治疗组（R + C 组）；同时6只 db/+小鼠作为阴性对照组（ND 组）。治疗16周后，观察各组小鼠体重、血糖、血肌酐水平、尿白蛋白排泄率及肾组织病理指标的差异。结果与 D 组比较，雷帕霉素、坎地沙坦及两者联合治疗均可显著延缓 db/ db 小鼠体重增长，差异有统计学意义（P <0.01）。治疗16周后，R 组、C 组24 h 尿白蛋白排泄率、血肌酐水平均低于 D 组，R + C 组低于 R 组和 C 组，差异有统计学意义（P <0.05）。与 ND 组比较，糖尿病各组肾小球体积、系膜区基质显著增加，雷帕霉素、坎地沙坦及两者联合治疗均可显著延缓肾小球体积增大及系膜基质增加；与 R组、C 组比较，R + C 组肾小球体积及系膜区基质占肾小球面积百分比均明显降低，差异有统计学意义（P <0.05）。电镜结果显示 D 组肾小球基底膜出现弥漫性或节段性增厚，雷帕霉素、坎地沙坦及两者联合治疗均可显著延缓肾小球基底膜增厚。结论雷帕霉素联合坎地沙坦可进一步降低尿白蛋白排泄率及血肌酐水平，延缓肾小球体积增大及系膜区基质沉积；在减轻糖尿病肾损害、延缓糖尿病肾病进展方面具有协同作用。
목적관찰 mTOR 억제제（뢰파매소）연합혈관긴장소Ⅱ수체조체제（감지사탄）대당뇨병신병적작용。방법24지2형당뇨병모형 db/ db 소서수궤균등분위당뇨병조（D조）、뢰파매소치료조（R 조）、감지사탄치료조（C 조）、뢰파매소+감지사탄치료조（R + C 조）；동시6지 db/+소서작위음성대조조（ND 조）。치료16주후，관찰각조소서체중、혈당、혈기항수평、뇨백단백배설솔급신조직병리지표적차이。결과여 D 조비교，뢰파매소、감지사탄급량자연합치료균가현저연완 db/ db 소서체중증장，차이유통계학의의（P <0.01）。치료16주후，R 조、C 조24 h 뇨백단백배설솔、혈기항수평균저우 D 조，R + C 조저우 R 조화 C 조，차이유통계학의의（P <0.05）。여 ND 조비교，당뇨병각조신소구체적、계막구기질현저증가，뢰파매소、감지사탄급량자연합치료균가현저연완신소구체적증대급계막기질증가；여 R조、C 조비교，R + C 조신소구체적급계막구기질점신소구면적백분비균명현강저，차이유통계학의의（P <0.05）。전경결과현시 D 조신소구기저막출현미만성혹절단성증후，뢰파매소、감지사탄급량자연합치료균가현저연완신소구기저막증후。결론뢰파매소연합감지사탄가진일보강저뇨백단백배설솔급혈기항수평，연완신소구체적증대급계막구기질침적；재감경당뇨병신손해、연완당뇨병신병진전방면구유협동작용。
Objective To observe whether the combination of mTOR inhibitor(rapamycin)and angiotensin Ⅱ re-ceptor blocker(candesartan)can protect diabetic nephropathy better. Methods Twenty four db / db mice were ran-domly divided into 4 groups,as follows:db / db mice without intervention(group D),db / db mice with administra-tion of rapamycin(group R),db / db mice with administration of candesartan(group C),and db / db mice with ad-ministration of the combination of rapamycin and candesartan(group R + C). Six age-matched nondiabetic db / +mice served as controls(group ND). After a follow-up of 16 weeks,the biochemical indicators including body weight,blood glucose,serum creatinine levels were observed. The difference of urinary protein excretion rates and renal pathological indicators of each group were also observed. Results Compared with the group D,the group R, group C,and group D + C therapy could significantly delay the db / db mice weight gain,and the difference was statistically significant(P < 0. 01). After 16 weeks of treatment,24 h urinary protein excretion rate and serum cre-atinine in the group R and group C,were lower than in group D;24 h urinary protein excretion rate and serum cre-atinine in the group R + C were lower than in the R group and C group and the difference was statistically signifi-cant. Compared with the ND group,glomerular volume and the matrix of mesangial area were significantly increased in diabetic groups;Rapamycin,candesartan,and the combination therapy could significantly delay the glomerular volume gain and mesangial matrix accumulation;compared with R group or C group,the glomerular volume and the percentage of mesangial matrix in total glomerular area were significantly lower in R + C group and the difference was statistically significant( P < 0. 05). Electron microscopy results also showed that the glomerular basement membrane was diffusely or segmentally thickened in group D,and the rapamycin,candesartan and the combination therapy could significantly decrease the thickenness of the glomerular basement membrane. Conclusion The com-bination of rapamycin and candesartan can further reduce the rate of urinary protein excretion and serum creatinine levels,delay glomerular volume gain and mesangial matrix deposition. The combination of rapamycin and candesar-tan have a synergistic effect on reducing the diabetic kidney damage and delaying the progress of diabetic nephropa-thy.