目的 观察番茄红素对糖尿病性肾病的治疗作用及其可能的作用机制.方法 采用高糖高脂饮食加链脲佐菌素法制备2型糖尿病大鼠模型.2型糖尿病大鼠分别ig给予番茄红素5,10和20 mg·kg -1每天1次,连续8周.8周后取尾尖血用罗氏血糖仪测定空腹血糖(FBG)含量,腹主动脉采血后分离血清和血浆,用全自动生化分析仪测定血清肌酐(Scr)、尿素氮(BUN)和24 h尿蛋白(UP)含量,放免法检测血浆胰岛素(Ins)、血管紧张素Ⅱ(AngⅡ)和肾组织AngⅡ含量.HE染色观察肾组织病理形态的变化,RT-PCR法检测肾组织血管紧张素转换酶( ACE)和ACE2 mRNA的表达,Western印迹法检测肾组织ACE2蛋白的表达.结果 与正常对照组相比,模型对照组FBG,Ins,Scr,BUN,AngⅡ和24 h UP含量均明显升高(P＜0.05)；与模型对照组相比,番茄红素10和20 mg·kg-1组Scr,BUN,AngⅡ和24 h UP含量均显著降低,Scr由(54.2±4.3) μmol·L-1分别降低到40.3±2.0和(34.4±3.8) μmol·L-1,BUN由(17.7±2.3) mmol·L-1分别降低到15.5±1.2和(13.1±0.5)mmol·L-1,血浆中AngⅡ由(858±56 )ng·L-1分别降低到680±62和(623 ±64) ng·L-1,肾组织AngⅡ由(19.8±2.9)ng·g-1分别降低到16.7±2.6和(13.6±2.4)ng·g-1蛋白,24 h UP由(16.4 ±3.5)mg分别降低到13.7 ±1.9和(9.9±2.3)mg(P ＜0.05).与正常对照组相比,模型对照组ACE2,ACE mRNA和ACE2蛋白表达水平显著降低(P＜0.01),与模型对照组相比,番茄红素5,10和20 mg· kg -1组ACE2 mRNA和蛋白表达水平则显著升高(P＜0.05),其中番茄红素20 mg· kg-1组效果更为明显(P＜0.01)；ACE mRNA表达水平与模型对照组无明显差异.结论 番茄红素能降低糖尿病模型大鼠蛋白尿,改善肾功能,减轻肾组织病理变化,增强肾组织ACE2 mRNA和蛋白的表达,提示番茄红素对糖尿病性肾病的治疗作用可能与抑制肾局部肾素-血管紧张素系统的途径有关.%OBJECTIVE To investigate the therapeutic effect of lycopene on kidney injury in diabetic model rats and its possible mechanism. METHODS The type 2 diabetes rat model was prepared by high-carbohydrate and high-fat diet, and streptozotocin (STZ) ip given. Then the diabetic rats were ig given lycopene 5, 10, and 20 mg·kg-1 , respectively, once daily, for 8 weeks. The concentration of fasting blood glucose (FBG) was determined by Roche blood glucose meter.Serum and plasma samples were taken from the abdominal aorta before the concentration of serum creatinine (Scr) , urea nitrogen (BUN) , and 24-hour urine protein (UP) was determined by an automatic biochemical analyzer. The concentration of plasma insulin ( Ins) and angiotensin Ⅱ ( Ang Ⅱ ) in plasma and renal tissue was measured by radioimmunoassay. The pathological changes of renal tissue were observed by HE staining. Expressions of angiotensin converting enzyme ( ACE) mRNA, ACE2 mRNA and ACE2 protein in renal tissue were measured by RT-PCR and Western blotting, respectively. RESULTS Compared with normal control group, the concentration of FBG, Ins, Scr, BUN, AngⅡ and UP in model group was all significantly higher (P＜0.05, P＜0.01). Compared with model group, Scr, BUN, Ang Ⅱ and UP in lycopene 10 and 20 mg·kg-1 groups were greatly decreased (P＜0. 05). Compared with model group, Scr in lycopene 10 and 20 mg·kg-1 groups decreased from 54. 2 ±4. 3 to 40. 3 ±2.0 and (34.4 ±3. 8)μmol·L-1 , respectively. BUN from 17.7 ±2. 3 to 15. 5 ± 1. 2 and ( 13. 1 ±0. 5) mmol·L-1, plasma Ang Ⅱ from 858 ±56 to 680 ±62 and (623 ±64)ng·L-1, Ang Ⅱ in renal tissue from 19.8 ±2.9 to 16.7 ±2.6 and (13.6±2.4)ng·g-1 protein, UP from 16.4 ±3.5 to 13.7 ±1.9 and (9.9 ±2.3)mg (P＜ 0.05). The expression of ACE mRNA, ACE2 mRNA and ACE2 protein in model group greatly decreased compared to normal control group ( P＜0.01). ACE2 mRNA and protein levels in lycopene 5, 10, and 20 mg·kg-1 groups were obviously up-regulated (P＜0. 05) especially in lycopene 20 mg·kg-1 group (P＜0. 01). There was little change in ACE mRNA in model and lycopene groups. CONCLUSION Lycopene can decrease proteinuria, improve the renal function, reduce the renal pathological damage and up-regulate the expression of ACE2 mRNA and protein in diabetic model rats. The possible mechanism is that lycopene can block pathways of the local renin-angiotensin system in kidneys.
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