摘要
目的:探讨大黄酸对STZ糖尿病大鼠肾组织转化生长因子β(TGF-β)及其Ⅰ型(TβRⅠ)、Ⅱ型受体(TβRⅡ)的影响及其可能作用机制。方法:采用STZ腹腔注射法建立糖尿病动物模型。96只3月龄雌性Wistar大鼠随机分为正常对照组,糖尿病模型对照组,低剂量大黄酸治疗组[35mg/(kg·d)]和高剂量大黄酸治疗组[70mg/(kg·d)]。第4、8、12周各组处死8只大鼠并收集标本,记录体重、左肾重,检测血糖、血肌酐、24h尿蛋白排泄量,ELISA法检测24h尿TGF-β水平。RT-PCR法、Westernblot法及免疫组化法检测肾组织TGF-β、TβRⅠ、TβRⅡ、FN及葡萄糖转运蛋白1(GLUT1)mRNA及蛋白质表达水平。结果:糖尿病模型大鼠血糖及24h尿蛋白排泄量明显增高,肾组织TGF-β、TβRⅠ、TβRⅡ及FNmRNA表达水平在12周内表现进行性升高,肾组织GLUT1mRNA水平在12周内表现为先下调,再上调的趋势。而肾组织TGF-β、TβRⅠ、TβRⅡ、FN及GLUT1蛋白质表达水平均在8周时达到高峰值,12周时表现下降。大黄酸治疗可时间-剂量依赖性降低糖尿病大鼠血糖水平,减少24h尿蛋白排泄量,血肌酐水平下降,使肾重指数下降。大黄酸治疗可时间-剂量依赖性下调糖尿病大鼠肾组织TGF-β、TβRⅠ、TβRⅡ、FN及GLUT1mRNA及蛋白质的表达水平。结论:大黄酸可通过降低糖尿病大鼠血糖水平,一方面直接减少TGF-β的合成,另一方面通过抑制己糖胺通路异常活化,抑制GLUT1的产生及其功能活性,减少TGF-β的产生,从而下调TβRⅠ、TβRⅡ表达,降低肾内TGF-β系统活性,延缓糖尿病肾病的发展。
Objective：Rhein has been proved effective in reducing mesangium matrix formation and inhibitive of the up-regulated glucose transporting in mesangial cell in diabetic rats. In this study, we investigated the effects of rhein on renal expression of transforming growth factor β （TGF-β） and its receptors type Ⅰ （TβR Ⅰ ） and type Ⅱ （TβR Ⅱ ） in streptozotocin （ STZ）-induced diabetic rats. Methodology：An animal model of diabetes was established by intraperitoneal injection of STZ. Ninety-six adult female Wistar rats were divided randomly into normal control group, diabetic control group, low-dose rhein treated group [ 35 mg/（kg·d） ] and high-dose rhein treated group [70 mg/（kg·d） ]. At the end of the 4th-week, the 8th-week and the 12th-week, eight rats in each group were sacrifised, and data of parameters as body weight, left kidney weight, serum glucose, serum creatinine, and 24-hour urinary protein excretion were collected. The urinary level of TGF-β was detected with ELISA. Renal mRNA and protein expression of TGF-β, TβR Ⅰ , TβR Ⅱ , FN and GLUT1 were measured with reverse transcriptase-polymerase chain reaction （RT-PCR） , western blot and immunohistochemical techniques. Results： In diabetic control group, serum glucose level and 24h urinary protein excretion rate were increased significantly. Renal expression of TGF-β, TβR Ⅰ , TβR Ⅱ and FN protein, and renal expression of both GLUT1 mRNA and protein peaked at the 8th-week of observation. In diabetic rats treated with rhein, the serum glucose level, the serum creatine level, 24h urine protein excretion and renal/body weight index were reduced time- and dose-dependently. The renal mRNA and protein expression of TGF-β, TβR Ⅰ , TβR Ⅱ , FN and GLUTⅠ were all down-regulated time- and dose-dependently. Conclusion： Rhein ameliorates renal lesion in diabetic rats, by decreasing serum glucose level and renal mesangial matrix. Rhein directly suppressed synthesis of TGF-β and expression of TGF-β receptors （TβR Ⅰ and TβR Ⅱ ）. The mechanism of rhein＇effect might be related to the suppression of up-regulated hexosamine biosythesis pathway and to the suppression of over-expression of GLUT1.
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
2006年第2期101-111,143,共12页
Chinese Journal of Nephrology,Dialysis & Transplantation
关键词
大黄酸
糖尿病肾病
转化生长因子Β
葡萄糖转运蛋白1
rhein diabetic nephropathy transforming growth factor β glucose transporter protein 1
