Effect of Triptolide on Expression of Oxidative Carbonyl Protein in Renal Cortex of Rats with Diabetic Nephropathy

The traditional Chinese medicine（Tripterygium wilfordii Hook.f., TWH） has been clinically used to treat primary and secondary renal diseases and proteinuria for nearly 40 years. However, there is a rare literature about the effect of triptolide（the main active ingredient of TWH） on the expression of oxidative carbonyl protein（OCP） in diabetic nephropathy（DN）. This study aimed to provide experimental evidence for triptolide treatment on DN through its effect on the expression of OCP, in order to investigate the effects of triptolide on the expression of OCP in rats with DN. Sixty SD rats were randomly divided into five groups： control group, high-dose triptolide（Th） group, low-dose triptolide（Tl） group, DN model group, and positive control（benazepril） group. The DN model was established using streptozotocin. Urinary protein excretion, fasting blood glucose（FBG）, superoxide dismutase（SOD） in renal homogenate, malondialdehyde（MDA） in renal homogenate and renal nitrotyrosine by immunohistochemistry, and the expression of OCP by oxyblotimmune blotting were detected. In the DN model group, rat urinary protein excretion and renal MDA were significantly increased, while renal SOD significantly decreased and nitrotyrosine expression was obviously upregulated in the kidney. After triptolide treatment, 24-h urinary protein excretion（61.96±19.00 vs. 18.32±4.78 mg/day, P〈0.001）, renal MDA（8.09±0.79 vs. 5.45±0.68 nmol/L, P〈0.001）, and nitrotyrosine expression were decreased. Furthermore, renal OCP significantly decreased, while renal SOD（82.50±19.10 vs. 124.00±20.52 U/L, P〈0.001） was elevated. This study revealed that triptolide can down-regulate the expression of OCP in the renal cortex of DN rats.

糖尿病肾病患者蛋白氧化损伤的研究

目的检测糖尿病肾病不同阶段患者血清晚期氧化蛋白产物水平及蛋白羰基含量,评价蛋白氧化损伤程度。方法根据24小时尿白蛋白定量将糖尿病患者分为单纯糖尿病组(DM组)、糖尿病早期肾病组(DN1组)、糖尿病肾病组(DN2组),并设健康对照组(NC组),检测各组血清晚期氧化蛋白产物(advanced oxidation prote inproducts,AOPPs)、蛋白质羰基含量(prote in carbonyl,PCO)水平。结果DM组血AOPPs、PCO较NC组明显升高,DN组患者血AOPPs、PCO较DM组明显升高,且随着肾病的进展AOPPs、PCO逐渐升高,组间差异均具有统计学意义(P<0.05)。结论糖尿病肾病患者蛋白氧化损伤较单纯糖尿病患者明显加重,而且随着糖尿病肾病的进展,蛋白氧化损伤进一步加重,蛋白氧化损伤产物积累增多。

己酮可可碱对糖尿病大鼠肾脏保护作用及其机制研究

目的：探讨己酮可可碱（PTX）对糖尿病（DM）大鼠肾脏保护作用及其抗氧化应激的机制。方法将50只清洁级健康雄性SD大鼠随机数字表法分为正常对照组、DM组、PTX低剂量（PTXl）组、PTX高剂量（PTXh）组、贝那普利组（Ben组）等5组，使用链脲佐菌素建立DM模型，检测24 h尿蛋白定量、肾匀浆超氧化物歧化酶（SOD）、丙二醛（MDA）和肾组织硝基化酪氨酸（NT）、肾皮质氧化羰基化蛋白（OCP）,各组大鼠每天灌胃1次，连续12周。正常对照组和糖尿病组，用等量的饮水灌胃；PTXl组，以PTX 30 mg/（kg·d）灌胃；PTXh组，以PTX 50 mg/（kg·d）灌胃；Ben组，以贝那普利3 mg/（kg·d）灌胃。组间比较采用方差分析。结果实验12周后，与正常对照组相比，DM组、PTXl组、Ben组肾SOD水平均显著下降（F=4.687，P〈0.05）；而与DM组相比，PTXh组大鼠肾SOD水平显著升高（（87±9）比（121±27）U/L, t=3.64，P〈0.05）。与正常对照组相比，其他各组大鼠肾MDA水平均显著升高（F=9.803，均P〈0.05）；与糖尿病组相比，PTXh组、PTXl组、Ben组大鼠肾MDA水平均有非常显著性下降（t=-2.59、-2.59、-2.49，均P〈0.05）。糖尿病组肾病理损伤严重、肾小球系膜细胞的胞质中NT的表达显著增加。PTXh组肾病理损伤显著减轻、肾NT的表达明显减少，PTXl组、Ben组肾病理损伤减轻、肾NT的表达减少。与正常对照组相比，糖尿病组、PTXl组和Ben组肾皮质OCP表达均显著升高（t=9.43、2.51、2.34，均P〈0.05）,而PTXh组OCP表达与正常对照组差异无统计学意义（t=1.834，P〉0.05）。结论己酮可可碱对糖尿病大鼠肾脏保护作用显著，该作用与抗氧化应激有关。