CAJ | 학술논문

目的观察糖尿病肾组织肿瘤坏死因子(TNF-α)、核因子(NF-κB)的表达及其与肾组织细胞凋亡关系以及雷帕霉素对其的影响.方法将20只GK大鼠随机分为DM组(n＝10)、DMR组(n＝10),10只Wistar大鼠作为NC组.DMR组予以6mg/kg雷帕霉素灌胃,DM与NC组仅给予等量生理盐水灌胃.TUNEL法检测肾组织细胞凋亡.免疫组织化学法(IHC)检测肾组织TNF-α和NF-κB的表达.结果 TUNEL法显示,NC组肾组织未见明显的凋亡细胞;4周及8周DM组凋亡数呈进行性增多(P＜0.01).IHC显示,NC组肾组织TNF-a、NP-k Bp65有轻微阳性表达;4周、8周DM组NF-k Bp65、TNF-α表达有逐渐上升的趋势,均显著高于正常对照组(P＜0.01).NF-κBp65、TNF-α阳性表达呈正相关(P＜0.01);肾组织NF-α和NF-κBp65表达与肾组织细胞凋亡之间均呈正相关(P＜0.01);与DM组比较,DMR组4周、8周组肾组织TNF-α和NF-κBp65的过度表达均被显著抑制(P＜0.01),肾组织细胞凋亡数显著减少(P＜0.01).结论 NP-κB及其诱导的TNF-α在糖尿病肾病损伤中发挥重要作用,雷帕霉素可能通过抑制NP-kB和TNF-α的表达减少减轻肾组织细胞凋亡.
목적 관찰당뇨병신조직종류배사인자(TNF-α)、핵인자(NF-κB)적표체급기여신조직세포조망관계이급뢰파매소대기적영향.방법 장20지GK대서수궤분위DM조(n＝10)、DMR조(n＝10),10지Wistar대서작위NC조.DMR조여이6mg/kg뢰파매소관위,DM여NC조부급여등량생리염수관위.TUNEL법검측신조직세포조망.면역조직화학법(IHC)검측신조직TNF-α화NF-κB적표체.결과 TUNEL법현시,NC조신조직미견명현적조망세포;4주급8주DM조조망수정진행성증다(P＜0.01).IHC현시,NC조신조직TNF-a、NP-k Bp65유경미양성표체;4주、8주DM조NF-k Bp65、TNF-α표체유축점상승적추세,균현저고우정상대조조(P＜0.01).NF-κBp65、TNF-α양성표체정정상관(P＜0.01);신조직NF-α화NF-κBp65표체여신조직세포조망지간균정정상관(P＜0.01);여DM조비교,DMR조4주、8주조신조직TNF-α화NF-κBp65적과도표체균피현저억제(P＜0.01),신조직세포조망수현저감소(P＜0.01).결론 NP-κB급기유도적TNF-α재당뇨병신병손상중발휘중요작용,뢰파매소가능통과억제NP-kB화TNF-α적표체감소감경신조직세포조망.
Objective To observe whether rapamycin can relieve apoptosis of renal cells in GK diabetic rats . Methods Ten male Wistar rats and ten male GK rats were randomly divided into three groups: normal control (NC, n=10 ) , diabetics (DM, n=10 ) and diabetics treated with rapamycin(DMR，n=10）.The renal cell apoptosis was measured by TUNEL. The expression of TNF-α and NF-κB in renal tissue were examined by immunohistochemical stain . The correlation between TNF-α and NF-κB were analyzed by Pearson method, and the interrelation between TNF-α, NF-κB and renal tissue apoptotic cells was analyzed by Spearman method. Results The apoptotic renal cell number was more in DM 4w and 8w groups than in NC group and in rapamycin-treated DM group (DMR) (all P<0.05) and was more in 8w group than in 4w group in NC, DM and DMP groups, and showed similarities between NC and DMR group. The expressions of TNF-α and NF-κB were higher in DM 4w and 8w group than in NC and DMR 4w and 8w groups (all P<0.05) ,and was higher in 8w than in 4w group of NC, DM and DMR groups. The expression of NF-κB and TNF-α was positively correlated with renal cell apoptosis. Rapamycin treated DM group versus DM group showed a suppression of over-expression of renal TNF-α and NF-κB p65, and of renal cell apoptosis (all P<0.01). Conclusions The NF-κB and TNF-α expression play an important role in development of diabetic nephropathy. Rapamycin has some renal protective effect on diabetes in rats, partly through down-regulating the NF-κB and TNF-α expression.