CAJ | 학술논문

目的探讨N-乙酰半胱氨酸(NAC)对糖尿病肾病(DN)大鼠肾皮质转化生长因子(TGF-β1)表达的影响.方法制备DN大鼠模型,将动物随机分为正常对照组、DN组和NAC组.8周后测定大鼠尿白蛋白排泄率,免疫组化和RT-PCR方法检测肾皮质TGF-β1的表达水平,观察肾脏标本病理变化.结果 (1)DN组和NAC组尿白蛋白排泄率与正常对照组比较明显增多[(1268.3±297.5)μg/24 h和(315.9±86.8)μg/24 h比(31.2±8.9)μg/24 h,q值分别为29.85、16.76,均P＜0.01];肾皮质TGF-β1表达水平升高,肾小球系膜区免疫组化指数7.35±1.17和3.87±0.71比1.95±0.34(q值分别为l0.75、5.82,均P＜0.01),肾小管间质区免疫组化指数21.21±3.78和10.67±1.86比3.62±0.79(q值分别为15.20、11.36,均P＜0.01),肾皮质mRNA表达量0.72±0.06和0.45±0.05比0.23±0.04(q值分别为9.13、7.45,均P＜0.01),肾脏病理改变明显;(2)与DN组比较,NAC组尿白蛋白排泄率减少(q=8.17,P＜0.01),肾皮质TGF-β1的表达水平降低[肾小球系膜区免疫组化指数(q=4.97,P＜0.01),肾小管间质区免疫组化指数(q=6.86,P＜0.01),肾皮质mRNA表达量(q=3.69,P＜0.05)]和肾脏病理病变轻;(3)NAC组大鼠肾皮质TGF-β1 mRNA的表达量与尿白蛋白排泄率水平正相关(r=0.749,P＜0.05).结论 NAC对DN大鼠肾脏有保护作用,其部分机制与抑制TGF-β1表达有关.
목적 탐토N-을선반광안산(NAC)대당뇨병신병(DN)대서신피질전화생장인자(TGF-β1)표체적영향.방법 제비DN대서모형,장동물수궤분위정상대조조、DN조화NAC조.8주후측정대서뇨백단백배설솔,면역조화화RT-PCR방법검측신피질TGF-β1적표체수평,관찰신장표본병리변화.결과 (1)DN조화NAC조뇨백단백배설솔여정상대조조비교명현증다[(1268.3±297.5)μg/24 h화(315.9±86.8)μg/24 h비(31.2±8.9)μg/24 h,q치분별위29.85、16.76,균P＜0.01];신피질TGF-β1표체수평승고,신소구계막구면역조화지수7.35±1.17화3.87±0.71비1.95±0.34(q치분별위l0.75、5.82,균P＜0.01),신소관간질구면역조화지수21.21±3.78화10.67±1.86비3.62±0.79(q치분별위15.20、11.36,균P＜0.01),신피질mRNA표체량0.72±0.06화0.45±0.05비0.23±0.04(q치분별위9.13、7.45,균P＜0.01),신장병리개변명현;(2)여DN조비교,NAC조뇨백단백배설솔감소(q=8.17,P＜0.01),신피질TGF-β1적표체수평강저[신소구계막구면역조화지수(q=4.97,P＜0.01),신소관간질구면역조화지수(q=6.86,P＜0.01),신피질mRNA표체량(q=3.69,P＜0.05)]화신장병리병변경;(3)NAC조대서신피질TGF-β1 mRNA적표체량여뇨백단백배설솔수평정상관(r=0.749,P＜0.05).결론 NAC대DN대서신장유보호작용,기부분궤제여억제TGF-β1표체유관.
Objective To investigate the effects of N-acetylcysteine (NAC) on the expression of transforming growth factor-β1 (TGF-β1) in renal cortex of diabetic nephropathy rats.Methods A rat model of DN was established.The rats were randomly divided into control group,DN group and NAC group.After 8 weeks treatment,urinary albumin excretion rate (UAER) was determined.The expression of TGF-β1 in renal cortex was detected by immunohistochemistry and RT-PCR analysis.Pathomorphological changes of renal cortex were observed.Results (1)The levels of UA ER were significantly higher in DN group and NAC group [(1268.3±297.5) μg/24 h and (315.9-±86.8) μg/24 h] than in control group [(31.2±8.9) μg/24 h,q-29.85,16.76,both P＜0.01].The groups of DN and NAC versus group of control showed the increased levels of activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:7.35±1.17 and 3.87 ± 0.71 vs.1.95±0.34,q= 10.75,5.82,both P＜0.01];immune-histochemistry index of renal tubulointerstitium [21.21± 3.78 and 10.67±1.86 vs.3.62±0.79,q=15.20,11.36,both P＜0.01];the expression of mRNA in renal cortex[0.72±0.06 and 0.45±0.05 vs.0.23±0.04,q=9.13,7.45,both P＜0.01].The pathomorphological changes were significant in DN group and NAC group.(2)The NAC group versus DN group showed a decreased levels of UAER (q=8.17,P＜0.01),activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:q= 4.97,P＜0.01]immune-histochemistry index of renal tubulointerstitium (q = 6.86,P ＜ 0.01 );the expression of mRNA in renal cortex (q= 3.69,P＜0.05) and showed improvement of pathomorphology in renal cortex.(3) There was a significantly positive correlation between expression quantity of TGF-β1 mRNA in renal cortex and UAER level in NAC group(r= 0.749,P＜0.05).Conclusions The protective effects of NAC on the kidney of DN rats may be partly related with inhibition on the expression of TGF-β1.