黄虹 江缨 袁放 郑和昕 阮园 吴天凤

大蒜素对糖尿病肾病大鼠肾脏保护作用的实验研究

黄虹 江缨 袁放 郑和昕 阮园 吴天凤

目的 探讨大蒜素对糖尿病肾病大鼠肾脏的保护作用及其机制。方法 将60只雄性SD大鼠采用腹腔注射链脲佐菌素（STZ）的方法建立糖尿病肾病大鼠模型，造模成功的大鼠采用随机数字表法分为低、中、高剂量组[分别采用15、30、45mg/（kg·d）大蒜素混悬液灌胃]、贝那普利组[贝那普利17.5 mg/（kg·d）灌胃]和模型组（0.9%氯化钠溶液灌胃），各12只，另以10只SD大鼠0.9%氯化钠溶液灌胃为正常对照组,分别于用药的0、4、8、12周末检测大鼠空腹血糖（FBG）、血尿素氮（BUN）、血肌酐（Scr）和24h尿白蛋白排泄率（UAE）水平，12周末时检测大鼠体质量、肾质量、肾质量/体质量；采用电镜及Masson染色观察大鼠肾组织病理学变化；采用Western blot法检测肾组织转化生长因子-β1（TGF-β1）、I型胶原（Collagen I）及p-ERK1/2蛋白的表达强度。结果 12周末时，高剂量组大鼠的肾质量/体质量、FBG、Scr、BUN、UAE低于模型组（均P＜0.05），且肾小球肥大、系膜细胞增生、肾小球变形病变明显减轻，TGF-β1、Collagen I及p-ERK1/2的蛋白表达均显著下降（P＜0.01）。结论 大蒜素可降低糖尿病肾病大鼠肾组织TGF-β1、Collagen I及p-ERK1/2的表达，具有一定的肾保护作用。

大蒜素 糖尿病肾病 TGF-β1 p-ERK1/2

【 Abstract】 Objective To investigate the renal protective effect and mechanism of allicin on rats with diabetic nephropathy. Methods Diabetic nephropathy model were established by intraperitoneal injection of streptozotocin(STZ)in 60 male SD rats,then the animals were randomly divided into 5 groups with 12 in each group.Rats in low,middle and high dose allicin groups were given 15,30,45 mg/kg·d allicin,respectively,rats in benazepril group were given 17.5 mg/kg·d benazepril by gavage and no drug was given to rats in model group.Ten SD male rats were included in experiment as normal control group. Fasting blood glucose(FBG),serum urea nitrogen(BUN),serum creatinine(Scr)and 24-h urine albumin excretion(UAE)were detected at the 4,8,12th weeks.At the end of 12 weeks animals were sacrificed,the body mass,kidney mass,and the ratio of kidney mass/body mass of rats were detected.Histopathological changes of kidney were observed by light microscope,electron microscope,and Masson staining.Expression of collagen I,transforming growth factor-β1(TGF-β1)and phosphorylation of extracellular signal-regulated kinase 1/2(p-ERK1/2)were examined by Western blot. Results Compared with model group,the kidney mass/body mass,FBG,Scr,BUN and 24-h UAE in high dose allicin group were significantly decreased at the end of wk 12(P＜0.05),the glomerular hypertrophy,mesangial cell proliferation,glomerular deformation lesions were significantly attenuated, and the expression of TGF-β1,collagen I and p-ERK1/2 protein were decreased significantly(P＜0.01). Conclusion Allicin may have a protective role in diabetic nephropathy rats,which is associated with the down-regulation of TGF-β1,collagen I and p-ERK1/2 expression.

【 Key words】 Allicin Diabetic nephropathy Transforming growth factor-β1 Phosphorylation of extracellular signal-regulated kinase 1/2

糖尿病肾病是糖尿病常见、严重的慢性并发症，也是导致终末期肾病的主要原因。我国终末期肾病患者的比例正逐年增加[1]，探讨糖尿病肾病的发病机制，寻找有效治疗的新靶点，对防治糖尿病肾病、延缓终末期肾病的进程具有重要意义。转化生长因子β1（TGF-β1）在糖尿病肾病中发挥重要作用，对肾细胞的分化、增生和细胞外基质的合成及降解具有很强的调控作用[2]；……