虫草菌粉对慢性马兜铃酸肾病大鼠模型肾间质纤维化的保护作用  

Protective effects of Hirsutella sinensis on renal interstitial fibrosis:experiment with rat model of chronic aristolochic acid nephropathy

作　　者：朱运锋[1] 谌贻璞[1] 芮宏亮[1] 董鸿瑞[1] 胡昭[2] 

机构地区：[1]卫生部中日友好医院肾病中心,北京山东大学齐鲁医院肾内科100029 [2]山东大学齐鲁医院肾内科

出　　处：《中华医学杂志》2007年第38期2667-2671,共5页National Medical Journal of China

基　　金：卫生部属(管)医疗机构临床学科重点项目(2005-2007年度)

摘　　要：目的研究虫草菌粉对慢性马兜铃酸肾病(CAAN)模型大鼠肾间质纤维化的拮抗作用。方法雄性 SD 大鼠随机分为对照组、模型组和虫草组;每组6只。于0、1、4、8及12周末分别检测大鼠体重、尿糖、尿蛋白定量和血清肌酐(SCr);并于第12周末处死大鼠留取肾组织,行 Masson 染色观察肾间质纤维化程度,逆转录实时聚合酶链反应和免疫组织化学方法检测肾组织中转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)、纤溶酶原激活物抑制物-1(PAI-1)、金属蛋白酶组织抑制物-1(TIMP-1)和Ⅰ型胶原(Col Ⅰ)mRNA 及蛋白质表达。结果模型组大鼠尿蛋白定量及 SCr 显著高于对照组(P<0.01及 P<0.05);12周时肾间质纤维化面积显著增加(P<0.01);肾组织内上述指标的 mRNA 及蛋白质表达显著上调(P<0.01)。与对照组相比,模型组大鼠肾组织 TGF-β1、CTGF、PAI-1、TIMP-1和 Col Ⅰ的 mRNA 表达分别上调4.19、2.66、6.12、3.09和7.03倍;蛋白质表达分别上调2.31、3.53、3.17、3.18和6.87倍。虫草组大鼠第12周时尿蛋白定量、SCr 及肾间质纤维化面积均显著低于模型组(P<0.05),上述高表达的 mRNA 及蛋白质指标均被显著抑制(P<0.05),与模型组相比,虫草组大鼠肾组织 TGF-β1、CTGF、PAI-1、TIMP-1和 Col Ⅰ的 mRNA 表达分别下调45%、41%、47%、48%和67%;蛋白质表达分别下调38%、39%、49%、46%和61%。结论虫草菌粉可通过抑制肾组织促细胞外基质(ECM)合成因子(TGF-β1、CTGF)及抗 ECM 降解因子(TIMP-1、PAI-1)生成,而改善 CAAN 的肾间质纤维化及肾功能。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 ofAristolochia 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-β1 （TGF-β1）, connective tissue growth factor （CTGF）, plasminogen activator inhibitor-1 （PAI-1）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and type Ⅰ collagen （ Col Ⅰ ） in the kidney tissues. Results Since the 1 st 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-β1, CTGF, PAI-1, TIMP-1, and Col I 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-

关 键 词：马兜铃酸 转化生长因子Β 肾炎 间质性 虫草菌粉 

分 类 号：R285.5[医药卫生—中药学]