摘要
目的观察长期高脂饲养对正常大鼠肾脏蛋白激酶C(PKC)活性的影响及复方中药的干预作用,并检测肾组织转化生长因子β1(TGFβ1mRNA)表达水平,探讨PKC活性变化在糖尿病肾病形成中的作用。方法健康SD雄性大鼠39只,随机分为4组:普通饲料组(第1组,正常对照组),高脂饲料组(2～4组),第2组为单纯高脂饮食组(模型组),第3组为二甲双胍干预组,第4组为复方中药(玉液汤化裁)干预组。6个月后取肾组织,氧化磷酸化法测PKC活性,RTPCR检测TGFβ1mRNA表达水平。结果高脂饮食6月后发生胰岛素抵抗,与正常对照组相比,模型组大鼠肾组织PKC活性,TGFβ1mRNA表达水平均明显增高(均P<0.01),同时大鼠肾脏出现早期糖尿病肾病的病理变化,如肾小球肥大,系膜基质增多等。与模型组相比,二甲双胍干预组及中药干预组胞膜PKC活性,肾组织TGFβ1mRNA表达水平均明显减少(均P<0.01),同时肾脏病理得到改善。结论长期高脂饲养可诱发大鼠胰岛素抵抗,并出现早期糖尿病肾病的病理变化;PKC/TGFβ信号途径参与早期糖尿病肾病的发病过程;复方中药(玉液汤化裁)可通过降低长期高脂饮食大鼠肾组织PKC活性及TGFβ1mRNA表达,保护肾组织,防治糖尿病肾病。
Objective To observe the effect of long-term high-fat feeding on protein kinase C（PKC） activity and intervention role of compound herbal medicine. We determined the expression of transforming growth factor β1 （TGFβ1 ） mRNA in kidney and assessed the role played by PKC activation on the development of diabetic nephropathy（DN）. Methods 39 healthy male Sprague Dawley（SD） rats were randomly divided into 4 groups： Group 1 received standard laboratory chow diet. Group 2 to group 4 were fed with the high fat diet. Mefformin（lOOmg/kg） was given to animals in group 3, whereas group 4 received compound herbal medicine（yu ye tang hua cai）. At the end of a 6-month period, kidneys were rapidly removed for the measurement of PKC activity and expression of TGFβ1 mRNA. Results After high-fat feeding for 6 months, rats from group 2 developed insulin resistance（IR）, which was associated with significant increase（ P 〈 0.01） in membrane PKC activity and TGFβ1 mRNA expression in kidneys when compared with the normal control group. In addition, the pathologic changes in early stage of DN, such as glomerular hypertrophy and mesangial matrix accu-mulation were found in rat kidneys of group 2. The treatment with mefformin or compound herbal medicine significantly blocked the increase in PKC activity and TGFβ1 mRNA expression（ P 〈 0.01 ） induced by high fat diet. Moreover, the renal pathological changes were found to be ameliorated. Conclusion Long-term high fat feeding can induce JR and the pathological changes may appear in early stage of DN. The signaling pathway triggered by PKC/TGFβ1 plays a pivotal role in the development of the early stage of DN which can be blocked by the compound herbal medicine（ yu ye tang hua cai）.
出处
《中国微循环》
北大核心
2006年第3期176-181,共6页
Journal of Chinese Microcirculation
基金
河北省卫生厅立项课题(编号:03182)
