维生素E对糖尿病大鼠肾脏的保护作用

目的探讨维生素E对糖尿病大鼠肾脏保护作用及其可能机制。方法实验动物分为正常对照组、链脲佐菌素诱导的糖尿病未治疗组、糖尿病给予维生素E（20mg.kg-1.d-1）治疗组，共观察8周。测定尿白蛋白排泄量(UAE)，内生肌酐清除率（Ccr）、血浆及肾脏组织一氧化氮（NO）、一氧化氮合成酶（NOS）、内皮素（ET）和肾小球蛋白激酶C（PKC）。结果2周时糖尿病未治疗组Ccr［(6.47±1.51)ml·min-1·kg-1］、尿白蛋白排泄量［(15.60±1.64)μg/24h］、NO［(37.30±3.77)μmol/L］、NOS［(34.89±3.83)U/L］及肾小球细胞膜PKC［(86.85±11.37)pmol·min-1·mgprotein-1］明显高于对照组，ET低于对照组。8周时糖尿病大鼠肾小球细胞膜PKC［(84.18±12.14)pmol·min-1·mgprotein-1］仍明显高于对照组，但NO［(22.75±2.89)μmol/L］及NOS［(21.34±1.92)U/L］低于对照组，ET高于对照组。给予维生素E治疗组8周时，Ccr［(4.46±0.49)ml·min-1·kg-1］及尿白蛋白量［(16.31±1.12)μg/24h］显著低于未治疗组，8周时肾小球细胞膜PKC［(65.19±8.83)pmol·min-1·mgprotein-1］，2周时NO［(33.13±3.77)μmol/L］及NOS［(30.16±2.89)U/L］明显低于未治疗组，维生素E治疗组2周时与8周时的NO及NOS下降幅度明显小于未治疗组。结论维生素E通过抑制蛋白激酶C可以纠正糖尿病早期的肾脏高滤过、高灌注，并与抑制肾脏NO合成有关，抑制蛋白激酶C活性对糖尿病肾病防治尤为重要。

Renal protective effects of vitamin E in diabetic rats

OBJECTIVE: To investigate the renal protective effect of vitamin E on streptozotocin induced diabetic rats, as well as the possible mechanism involved in. METHODS: Vitamin E 20 mg x kg(-1) x d(-1) was given to diabetic rats for 8 weeks.Urinary albumin excretion (UAE) was measured by radioimmunoassay. The changes of creatinine clearance rate (Ccr), nitric oxide(NO), nitric oxide synthase (NOS) and endothelin(ET) in the plasma and renal cortical tissue, membrane protein kinase C(PKC) in the renal glomeruli were observed. RESULTS: At two weeks, diabetic rats had supernormal Ccr(6.47 +/- 1.51) ml x min(-1) x kg(-1)], UAE(15.60 +/- 1.64) microg/24h], NO(37.30 +/- 3.77) micromol/L], NOS(34.89 +/- 3.83) U/L] and PKC(86.85 +/- 11.37) pmol x min(-1) x mg protein(-1)] of diabetic rats were increase but ET was decreased. At 8 weeks, PKC(84.18 +/- 12.14 ) pmol x min(-1) x mg protein(-1)] and ET of diabetic rats was increased significantly, but NO(22.75 +/- 2.89) micromol/L] and NOS(21.34 +/- 1.92) U/L] of diabetic rats was lowered. After treated with vitamin E, Ccr(4.46 +/- 0.49) ml x min(-1) x kg(-1)], UAE(16.31 +/- 1.12) microg/24h], PKC(65.19 +/- 8.83) pmol x min(-1) x mg protein(-1)] at 8 weeks were decreased significantly. Both NO(33.13 +/- 3.77) micromol/L] and NOS(30.16 +/- 2.89) U/L] in plasma and kidney tissue were lowered as compared with untreated diabetic group in two weeks. Vitamin E also delayed the NO and NOS lowering in 8 weeks. CONCLUSION: Vitamin E could ameliorate early diabetic renal hemodynamic abnormality via inhibiting PKC, in which inhibition of NO production might be involved. It is important to reduced the PKC activity so as to prevent or delay the development of diabetic nephropathy.