广防己肾毒性及配伍解毒实验研究

Experimental Study of Kidney Toxicity of the Aristolochia fangchi Y.C. Wu ex L.D. Chow et S.M.Hwang and Detoxication by Compatibility

目的:观察广防己水煎液的慢性肾毒性及其分别与大黄、川芎、桂枝、茯苓、黄芪等中药配伍后肾毒性的改善情况。方法:通过测定血肌酐(Scr)、尿β2-微球蛋白(β2-MG)、尿碱性磷酸酶(AKP)、尿溶菌酶(Lys)的含量,观察肾脏病理形态变化及肾脏表皮生长因子(EGF)、转化生长因子β1(TGF-β1)的蛋白表达,探讨广防己慢性肾毒性及不同配伍药物对其的拮抗作用。结果:与空白组对照,大剂量广防己组尿AKP明显升高(P<0.05);与大剂量广防己组对照,配伍桂枝组、黄芪组尿AKP明显降低(P<0.05)。肾病理检查发现大剂量组肾小管上皮细胞水肿。各组肾脏EGF蛋白的表达基本都是在肾小管呈弱阳性。大剂量组和配伍川芎组个别标本远曲小管TGF-β1蛋白的表达呈强阳性。结论:广防己按药典规定量长期服用未见肾损害,大剂量则对肾小管有轻度损伤;各配伍药物均可减轻其副作用,以桂枝、黄芪最为明显。

Objective： To observe the chronic toxicity of kidney caused by Aristolochia fangchi Y. C. Wu ex L D. Chow et S. M. Hwang. And amelioration by matching respectively with Rheum, Ligustieum ehuanxiong Hort. Cinnamomum cassia Presl ,Poria cocos （ Sehw. ） Wolf and Astragalus membranaeeus （ Fiseh. ） Bge. Methods ： Concentration of Scr, β2- MG , AKP and Lys were measured and pathologic ehangs of kidney and expression of EGF and TGF -β1 were observed in Rats. Results： Compared to blank group,the concentrations of AKP were significantly higher（ P 〈0.05） in high dosage group. Compared to the high dosage group, the concentrations of AKP were significantly lower（ P 〈 0.05 ） in the groups matching respectively with Cinnamomum cassia Presl and Astragalus memhranaeeus（ Fiseh. ）Bge. Edema of renal tubular epithelial Cell took place in high dosage group by pathologic examination of kidney. The expression of EGF was slight positive in renal tubules of all groups. The expression of TGFβ1 was strong positive in few distal convoluted tubules of the high dosage group and the group matching with Ligustieum ehuanxiong Holt. Conclusien： Kidney toxicity ofAristolochia fangchi Y. C. Wu ex L D. Chow et S. M. Hwang was lower at the dose of pharmacopeia hut aminimal pathologic changes of renal tubules could be produeted at higher dosage. The pathologic changes were more slight in compatibility groups ,especially the groups matching with Cinnamomum cassia Presl and Astragalus membranaeeus （ Fiseh. ） Bge respectively.