发酵虫草菌粉和泼尼松对急性马兜铃酸肾病大鼠肾小管Notch2/hes-1信号通路活化的影响

Effect of Fermented Cordyceps Powder and Prednisone on the Notch2/hes-1 Signaling Activation in the Kidney Tubules of Rats with Acute Aristolochic Acid Nephropathy

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DOI：10.7661/CJIM.2013.08.1116

中文关键词: 急性马兜铃酸肾病 Notch2/hes-1信号通路发酵虫草菌粉泼尼松细胞凋亡

英文关键词:acute aristolochic acid nephropathy Notch2/hes-1 signal pathway fermented Cordyceps powder prednisone apoptosis

基金项目:广西自然科学基金资助项目（No. 桂科自0832173）

作者	单位	E-mail
黄仁发,梁群卿,程新
吴金玉	广西中医药大学第一附属医院肾内科（南宁 530023）	wujinyu0109@sina.com

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中文摘要:

目的探讨发酵虫草菌粉及泼尼松对急性马兜铃酸肾病（acute aristolochic acid nephropathy，AAAN）大鼠肾小管上皮细胞Notch2/hes-1信号通路的影响。方法将50只SD大鼠随机分为正常组、模型组、发酵虫草菌粉组（CS组）、泼尼松组及CS加泼尼松组，每组10只。以马兜铃酸A纯品100 mg/（kg·d）连续灌胃3天建立AAAN模型。CS组予发酵虫草菌粉5.0 g/（kg·d）灌胃，泼尼松组予泼尼松0.5 mg/（kg·d）灌胃，CS加泼尼松组予两药联合灌胃，连续3周。检测各组大鼠肾功能［尿素氮（BUN）、肌酐（SCr）］，HE染色观察肾脏病理改变，TUNEL法检测肾小管上皮细胞凋亡，免疫组织化学法及Western blot法检测大鼠肾组织Notch2、Hes-1蛋白表达。结果 HE染色结果显示，正常组大鼠肾组织结构正常；模型组大鼠出现肾小管坏死改变；泼尼松组、CS组及CS加泼尼松组肾小管病理明显改善。与正常组比较，模型组大鼠BUN和SCr水平、肾小管间质半定量评分、凋亡细胞比例以及Notch2、Hes-1蛋白表达均显著升高（P<0.01）。与模型组比较，CS组、泼尼松组及CS加泼尼松组上述指标均显著降低（P<0.01）。以CS加泼尼松组降低更明显（P<0.05， P<0.01）。结论 Notch2/hes-1信号通路活化可能参与AAAN肾小管上皮细胞凋亡的发生。CS及泼尼松对AAAN有肾保护作用，但联合干预疗效更佳，其机制可能与抑制肾组织Notch2/hes-1信号通路活化有关。

英文摘要:

Objective To investigate the effect of both fermented Cordyceps powder （CS） and prednisone on the Notch2/hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy （AAAN）. Methods Totally 50 SD rats were randomly divided into 4 groups， i.e.， the normal group， the model group， the CS group， the prednisone group， and the CS plus prednisone group， 10 in each group. The AAAN rat model was induced by intragastric administration of pure aristolochic acid A at the daily dose of 100 mg/kg for 3 days. Rats in the CS group were administered with CS at the daily dose of 5.0 g/kg by gastrogavage， while those in the prednisone group were administered with prednisone at the daily dose of 0.5 mg/kg. Rats in the CS plus prednisone group were treated by CS and prednisone. All treatment lasted for 3 successive weeks. Kidney functions ［urea nitrogen （BUN） and serum creatinine （SCr）］ were detected. The pathological changes of kidneys were observed by Hematoxylin-Eosin staining. The apoptosis of the renal tubular epithelial cells was detected by TUNEL. The protein expressions of Notch2 and Hes-1 in the renal tissue were detected by immunohistochemical assay and Western blot. Results Results of HE staining showed the structure in the nephridial tissue was regular in rats of the normal group. The renal tubular necrosis occurred in the rats of the model group. The pathological changes of kidneys were obviously improved in the CS group， the prednisone group， and the CS plus prednisone group. Compared with the normal group， levels of BUN and SCr， semi-quantitative score of the tubular interstitial tissue， ratio of apoptotic cells， and expressions of Notch2 and Hes-1 proteins significantly increased in the model group （P<0.01）. Compared with the model group， the aforesaid indices significantly decreased in the 3 treatment groups （P<0.01）. All indices decreased most obviously in the CS plus prednisone group （P<0.05， P<0.01）. Conclusions Notch2/hes-1 signaling activation might be associated with apoptosis of renal tubular epithelial cells. Both CS and prednisone could play a nephroprotective role for AAAN. But CS plus prednisone could achieve the best effect. Inhabiting the Notch2/hes-1 signaling activation could be its nephroprotective mechanism.

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