CAJ | 학술논문

目的探讨吡咯烷二硫代氨基甲酸酯(PDTC)联合霉酚酸酯(MMF)对糖尿病大鼠肾脏协同保护作用及机制.方法链脲佐菌素(STZ)诱导糖尿病大鼠34只,并随机分为糖尿病未治疗组(D组),PDTC治疗组(P组), MMF治疗组(M组)和PDTC联合MMF治疗组(P+M组),以正常同龄大鼠作为对照组(C组).8周后测定血糖、血尿素氮、肌酐及24 h尿蛋白.处死动物后,称肾重并计算肾重指数(KI);光镜、电镜观察肾脏病理改变;免疫组化检测肾小球白细胞介素18(IL-18)、细胞间黏附分子1(ICAM-1)、肿瘤坏死因子的表达.结果 D组及各治疗组血糖、血尿素氮、肌酐、24 h尿蛋白、KI均高于C组(P＜0.05);各治疗组与D组相比,除血糖外,上述各指标均有明显改善(P＜0.05);P+M组24 h尿蛋白低于P和M组(P＜0.05).D组大鼠肾小球体积增大、系膜细胞增生、毛细血管基底膜增厚、足突融合, 各治疗组上述病理改变有不同程度减轻.D组IL-18、 ICAM-1、 TNF-α在肾小球的表达较C组增高(P＜0.05),各治疗组较D组表达下降(P＜0.05),其中P+M组IL-18、ICAM-1、TNF-α表达较M组下降显著(P＜0.05),IL-18、TNF-岜泶锝螹组下降(P＜0.05).结论 PDTC和MMF对糖尿病大鼠肾脏均有保护作用,二者联用较单药效果更好,其机制可能与抑制肾内炎性细胞因子表达有关.
목적 탐토필각완이류대안기갑산지(PDTC)연합매분산지(MMF)대당뇨병대서신장협동보호작용급궤제.방법 련뇨좌균소(STZ)유도당뇨병대서34지,병수궤분위당뇨병미치료조(D조),PDTC치료조(P조), MMF치료조(M조)화PDTC연합MMF치료조(P+M조),이정상동령대서작위대조조(C조).8주후측정혈당、혈뇨소담、기항급24 h뇨단백.처사동물후,칭신중병계산신중지수(KI);광경、전경관찰신장병리개변;면역조화검측신소구백세포개소18(IL-18)、세포간점부분자1(ICAM-1)、종류배사인자적표체.결과 D조급각치료조혈당、혈뇨소담、기항、24 h뇨단백、KI균고우C조(P＜0.05);각치료조여D조상비,제혈당외,상술각지표균유명현개선(P＜0.05);P+M조24 h뇨단백저우P화M조(P＜0.05).D조대서신소구체적증대、계막세포증생、모세혈관기저막증후、족돌융합, 각치료조상술병리개변유불동정도감경.D조IL-18、 ICAM-1、 TNF-α재신소구적표체교C조증고(P＜0.05),각치료조교D조표체하강(P＜0.05),기중P+M조IL-18、ICAM-1、TNF-α표체교M조하강현저(P＜0.05),IL-18、TNF-파학득점조하강(P＜0.05).결론 PDTC화MMF대당뇨병대서신장균유보호작용,이자련용교단약효과경호,기궤제가능여억제신내염성세포인자표체유관.
Objective To investigate protective effects of pyrrolidine dithiocarbamate (PDTC) and mycophenolate mofetil (MMF) on kidneys of diabetic rats and the possible mechanism. Methods Thirty-four streptozotocin-induced diabetic rats were randomly divided into 4 groups: diabetic aminals without treatment (D group), diabetic rats treated with PDTC (P group), diabetic rats treated with MMF (M group), diabetic rats treated with combined PDTC and MMF (P+M group), and normal rats were considered as control group (C group). Blood glucose, blood urea nitrogen (BUN), serum creatinine (Scr), and 24 h urinary protein (24 h UP) were detected at the end of treatment lasting for 8 weeks. Kidneys were weighed in order to measure kidney weight/body weight ratio (KI) after rats were killed. Pathological changes in the kidneys were observed by light microscope and electron microscope. Expressions of interleukin-18 (IL-18), intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in renal glomerulus were detected by immunohistochemical staining. Results Blood glucose, BUN, Scr, 24 h UP, KI were significantly higher in D, P, M and P+M groups than those in C group (all P＜0.05). BUN, Scr, 24 h UP, KI were significantly lower in P, M and P+M groups than those in D group (all P＜0.05). 24 h UP was reduced in P+M groups compared with P,M groups (P＜0.05). Pathological changes were attenuated in P,M and P+M groups compared with D group. Expressions of IL-18, ICAM-1, TNF-α in renal glomerulus were much higher in D group than those in C group (all P＜0.05) and were reduced in P, M and P+M groups compared with D group (all P＜0.05). Expressions of IL-18, ICAM-1, TNF-α in P+M group were lower than those in P group (all P＜0.05), while expressions of IL-18, TNF-α were lower than those in M group (both P＜0.05). Conclusion The protective effects on kidneys of diabetic rats produced by combined use of PDTC with MMF were much better than by the application of either PDTC or MMF alone. The mechanism appears to be related with suppressing expressions of inflammatory cytokines.