[Protective effects of Hirsutella sinensis on renal interstitial fibrosis: experiment with rat model of chronic aristolochic acid nephropathy].
[Protective effects of Hirsutella sinensis on renal interstitial fibrosis: experiment with rat model of chronic aristolochic acid nephropathy].
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DOI：
10.3760/j.issn:0376-2491.2007.38.002
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发表时间：
2007-10
影响因子：
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通讯作者：
Yun-feng Zhu;Yi-Pu Chen;H. Rui;Hong-rui Dong;Zhao-yong Hu
中科院分区：
文献类型：
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作者：
Yun-feng Zhu;Yi-Pu Chen;H. Rui;Hong-rui Dong;Zhao-yong Hu
目的研究中华毛蛭对慢性马兜铃酸肾病（CAAN）肾间质纤维化的保护作用。方法雄性SD大鼠18只，随机分为3组：模型组，每天早上灌胃满水马兜铃提取物（AmK），持续12周；干预组，每天早上灌胃马兜铃提取物，下午灌胃中国毛蛭悬液，每天1次，持续12周；对照组，只灌胃自来水。分别于第1、4、8、12周末测定体重、尿糖、24 h尿蛋白排泄量和血清肌酐（SCr）。12周末处死大鼠，取肾行病理检查。采用RT-PCR和免疫组化检测肾组织中转化生长因子- β 1 （tgf - β 1）、结缔组织生长因子（CTGF）、纤溶酶原激活物抑制剂-1 （PAI-1）、金属蛋白酶组织抑制剂-1 （TIMP-1）、I型胶原（ColI） mRNA和蛋白的表达。结果自第1周起，模型组大鼠尿蛋白排泄量和SCr水平均显著高于对照组（P < 0.01或0.05）。12周末，模型组大鼠间质纤维化相对面积明显增大（P < 0.01）。模型组tgf - β 1、CTGF、PAI-1、TIMP-1、ColI mRNA表达量分别上调4.19、2.66、6.12、3.09、7.03倍，蛋白表达量分别上调2.31、3.53、3.17、3.18、6.87倍（均P < 0.01）。12周时，干预组大鼠尿蛋白排泄量、SCr水平、间质纤维化相对面积均显著低于模型组（均P < 0.05）。干预组tgf - β、CTGF、PAI-1、TIMP-1、ColI mRNA表达水平均显著低于模型组（均P < 0.05），抑制率分别为45%、41%、47%、48%；干预组tgf - β、CTGF、PAI-1、TIMP-1、ColI蛋白表达水平均显著低于模型组（均P < 0.05），抑制率分别为38%、39%、49%、46%、61%。结论中华毛杆菌可抑制促细胞外基质（ECM）合成因子tgf - β 1和CTGF的产生以及拮抗ECM降解因子TIMP-1和PAI-1的产生，从而减轻CAAN的肾间质纤维化，改善肾功能。
OBJECTIVE To study the protective effects of Hirsutella sinensis on renal interstitial fibrosis in chronic aristolochic acid nephropathy (CAAN). METHODS Eighteen male SD rats were divided into 3 equal groups: model group, given the extract of Aristolochia manshuriensis Kom (AmK) by gavage in the morning everyday for 12 weeks, intervention group, given the extract of Amk in the morning and suspension of Hirsutella sinensis in the afternoon by gavage once a day for 12 weeks, and control group, receiving tap water only by gavage. Bodyweight, urinary glucose, 24 h urinary protein excretion, and serum creatinine (SCr) were measured at the ends of the 1st, 4th, 8th, and 12th weeks respectively. At the end of the 12th week, all the rats were sacrificed with their kidneys taken out to undergo pathological examination. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and type I collagen (ColI) in the kidney tissues. RESULTS Since the 1st week, the urinary protein excretion and SCr levels in the model group were significantly higher than those in the control group (P < 0.01 or 0.05). At the end of the 12th week, the relative area of interstitial fibrosis of the model group was significantly enlarged (P < 0.01). The mRNA expression levels of TGF-beta1, CTGF, PAI-1, TIMP-1, and ColI in the model group were up-regulated by 4.19, 2.66, 6.12, 3.09, and 7.03 times respectively, and their protein expression levels were up-regulated by 2.31, 3.53, 3.17, 3.18, and 6.87 times respectively (all P < 0.01). By the end of the 12th week, the urinary protein excretion, SCr level and the relative area of interstitial fibrosis in the intervention group were all significantly lower than those in the model group (all P < 0.05). The mRNA expression levels of TGF-beta, CTGF, PAI-1, TIMP-1, and ColIof the intervention group were all significantly lower than those of the model group (all P < 0.05) with the inhibition rates of 45%, 41%, 47%, 48%, and the protein expression levels of TGF-beta, CTGF, PAI-1, TIMP-1, and ColI of the intervention group were all significantly lower than those of the model group (all P < 0.05) with the inhibition rates of 38%, 39%, 49%, 46%, and 61% respectively. CONCLUSION Hirsutella sinensis can inhibit the production of TGF-beta1 and CTGF, factors that promote the extracellular matrix (ECM) synthesis and TIMP-1 and PAI-1, factors that antagonize ECM degradation in kidney tissues, thus alleviating renal interstitial fibrosis and improving renal function in CAAN.