N-乙酰半胱氨酸对糖尿病肾病大鼠肾皮质转化生长因子表达的影响

Effects of N-acetylcysteine on expression of transforming growth factor-β1 in diabetic nephropathy rats

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.

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.